bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac Thyrotropin-Releasing Hormone Mediates Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats
Authors: Schuman Mariano L. , Landa Maria S. , Toblli Jorge E. , Peres Diaz Ludmila S. , Alvarez Azucena L. , Finkielman Samuel , Paz Leonardo , Cao Gabriel , Pirola Carlos J. , García Silvia I.
Published: December 2010

Local thyrotropin-releasing hormone (TRH) may be involved in cardiac pathophysiology, but its role in left ventricular hypertrophy (LVH) is still unknown. We studied whether local TRH is involved in LVH of spontaneously hypertensive rats (SHR) by investigating TRH expression and its long-term inhibition by interference RNA (TRH-iRNA) during LVH development at 2 stages (prehypertrophy and hypertrophy). SHR and their control rats (WKY) were compared. Cardiac hypertrophy was expressed as heart/total body weight (HW/BW) ratio. TRH content (radioimmuno assay), preproTRH, TRH receptor type I, brain natriuretic peptide (BNP), and collagen mRNA expressions (real-time polymerase chain reaction) were measured. For long-term inhibition of TRH, TRH-iRNA was injected into the left ventricle (LV) wall for 8 weeks. Hearts were processed for morphometric studies and immunohistochemical analysis using antibodies against α-smooth muscle actin and collagen type III. LV preproTRH-mRNA abundance was similar in both strains at 7 weeks of age. At the hypertrophic stage (18 weeks old), however, there was a 15-fold increase in SHR versus WKY, consistent with a significant increase in tripeptide levels and the expression of its receptor. Specific LV-TRH inhibition at the prehypertensive stage with TRH-iRNA, which decreased >50% preproTRH expression and tripeptide levels, prevented LVH development as shown by the normal HW/BW ratio observed in TRH-iRNA–treated SHR. In addition, TRH-iRNA impeded the increase in BNP and type III collagen expressions and prevented the increase in cardiomyocyte diameter evident in mismatch iRNA-treated adult SHR. These results show for the first time that the cardiac TRH system is involved in the development of LVH in SHR.
Blood Pressure and Cerebral White Matter Share Common Genetic Factors in Mexican Americans
Authors: Kochunov Peter , Glahn David C. , Lancaster Jack , Winkler Anderson , Karlsgodt Kathrin , Olvera Rene L. , Curran Joanna E. , Carless Melanie A. , Dyer Thomas D. , Almasy Laura , Duggirala Ravi , Fox Peter T. , Blangero John
Published: December 2010

Elevated arterial pulse pressure and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially attributable to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican Americans. The patterns of whole-brain and regional genetic overlap between BP and fractional anisotropy were interpreted in the context the pulse-wave encephalopathy theory. We also tested whether regional pattern in genetic pleiotropy is modulated by the phylogeny of WM development. BP and high-resolution (1.7×1.7×3 mm; 55 directions) diffusion tensor imaging data were analyzed for 332 (202 females; mean age 47.9±13.3 years) members of the San Antonio Family Heart Study. Bivariate genetic correlation analysis was used to calculate the genetic overlap between several BP measurements (pulse pressure, systolic BP, and diastolic BP) and fractional anisotropy (whole-brain and regional values). Intersubject variance in pulse pressure and systolic BP exhibited a significant genetic overlap with variance in whole-brain fractional anisotropy values, sharing 36% and 22% of genetic variance, respectively. Regionally, shared genetic variance was significantly influenced by rates of WM development (
r
=−0.75;
P
=0.01). The pattern of genetic overlap between BP and WM integrity was generally in agreement with the pulse-wave encephalopathy theory. Our study provides evidence that a set of pleiotropically acting genetic factors jointly influence phenotypic variation in BP and WM integrity. The magnitude of this overlap appears to be influenced by phylogeny of WM development, suggesting a possible role for genotype-by-age interactions.
High-Order Spectral Filter for the Spherical-Surface Limited Area
Authors: Park Ja-Rin , Cheong Hyeong-Bin , Kang Hyun-Gyu
Published: December 2010

A high-order spectral filter for the spherical-surface limited-area domain, either window or sector type, is presented, where the window domain is finite both in longitude and latitude and the sector domain is finite in longitude, but is ranged from Pole to Pole in latitude. The data given in the physical domain are extended to either extended window or sector domain by padding artificial data that are appropriate for spectral decomposition with half-ranged Fourier series. The high-order filter equation of Laplacian operator type was split into first- or second-order spherical elliptic equations as in the global domain high-order spectral filter. Each low-order elliptic equation is discretized using half-ranged Fourier series both in longitudinal and latitudinal direction. Since the domain is of the spherical geometry, the window domain spectral filter consists of full matrices for each zonal wavenumber and thus performs filtering with O(N3) operation for N × N grids. On the other hand, the sector domain filter performs with efficient O(N2 logN) operation for the same grids, because the matrices can be constructed in tridiagonal form.

The error of the filter was analyzed using the eigenfunctions of the filter equation to get insights on data-extension parameters. The limited-area domain filters were tested with localized analytic function and the midlatitude observed data of meteorological variables, and the results were compared to those of the global domain filter. Accuracies of window and sector domain filters were found almost the same, and they turned out to vary with the filter parameters and the location and size of the domain. Application of the limited domain filters to the tropical cyclone initialization scheme showed very close performances to each other for the track and intensity forecasts.
A General Filter for Stretched-Grid Models: Application in Cartesian Geometry
Authors: Surcel Dorina , Laprise René
Published: December 2010

Global climate models with variable resolution are effective means to represent regional scales over an area of interest while avoiding the nesting issues of limited-area models. The stretched-grid approach provides a dynamical downscaling approach that naturally allows two-way interactions between the regional and global scales of motion. Concentrating the resolution over a subset of the earth’s surface increases computational efficiency and reduces the computational costs compared to global uniform high-resolution models; however, it does not come free of some problems related to the variation of resolution.

To address the issues associated with the stretching and anisotropy of the computational grid, a general convolution filter with a flexible response function is developed. The main feature of this filter is to locally remove scales shorter than a user-prescribed spatially varying length scale. The filtering effectiveness and computational efficiency of the filter can be custom tailored by an appropriate compromise between the filtering response and the width of the convolution stencil. This approach has been tested in one- and two-dimensional Cartesian geometry. It is shown that an effective filter can be obtained using a limited spatial stencil for the convolution to reduce computational cost, and that an adjustable spatially variable and nearly isotropic response can be obtained for application on variable grids.
Evidence for Use: Causal Pluralism and the Role of Case Studies in Political Science Research
Authors: Crasnow Sharon
Published: December 2010

Most contemporary political science researchers are advocates of multimethod research, however, the value and proper role of qualitative methodologies, like case study analysis, is disputed. A pluralistic philosophy of science can shed light on this debate. Methodological pluralism is indeed valuable, but does not entail causal pluralism. Pluralism about the goals of science is relevant to the debate and suggests a focus on the difference between evidence for warrant and evidence for use. I propose that case study research provides evidence for use through providing information that bears on the applicability of causal generalizations and risk assessment.
Videographic geographies: Using digital video for geographic research
Authors: Garrett Bradley L.
Published: December 2010

This article is a review of the ways in which human geography has engaged with film and video. Beginning with a look at the history of cinematic analysis within the discipline, the paper outlines different possible uses for digital video, focusing on its merits as a multisensory ethnographic method. The article encourages geographers to make the move from analysis to production, citing examples from successful recent projects which have done so, endorsing further integration of video into fieldwork and an increase in digital publication to create what we might call videographic geographies.
Hydrogen sulfide production by sulfate-reducing bacteria utilizing additives eluted from plastic resins
Authors: Tsuchida Daisuke , Kajihara Yusuke , Shimidzu Nobuhiro , Hamamura Kengo , Nagase Makoto
Published: December 2010

In the present study it was demonstrated that organic additives eluted from plastic resins could be utilized as substrates by sulfate-reducing bacteria. Two laboratory-scale experiments, a microcosm experiment and a leaching experiment, were conducted using polyvinyl chloride (PVC) as a model plastic resin. In the former experiment, the conversion of sulfate to sulfide was evident in microcosms that received plasticized PVC as the sole carbon source, but not in those that received PVC homopolymer. Additionally, dissolved organic carbon accumulated only in microcosms that received plasticized PVC, indicating that the dissolved organic carbon originated from additives. In the leaching experiment, phenol and bisphenol A were found in the leached solutions. These results suggest that the disposal of waste plastics in inert waste landfills may result in the production of H2S.
Improving the Safety and Effectiveness of Parenteral Nutrition
Authors: Boitano Megan , Bojak Shiva , McCloskey Shirley , McCaul David S , McDonough Megan
Published: December 2010

Parenteral nutrition (PN) is a high‐risk nutrition support modality. This article describes the approach taken by 1 hospital to improve safety and quality of this therapy as well as the challenges and obstacles to success. Process improvement strategies included revisions to the PN order form, education of clinicians (including physicians), increased collaboration between pharmacists and registered dietitians, and initiation of PN rounds during which PN patients were reviewed by the rounding team twice weekly. These strategies were spearheaded by clinicians with advanced certifications in nutrition support. These process changes positively impacted quality and costs. Comparison of baseline and follow‐up data showed improvement in compliance to mandatory safe practice standards, percentage of patients with appropriate indication for PN, adequote glycemic management, number of patients receiving PN within 10% of calorie needs, and appropriate laboratory monitoring. In addition to quality improvement, substantial cost savings were realized through decreased inappropriate PN use and timely transition to oral or enteral feeding. The average number of patients receiving PN decreased from approximately 15 to less than 5 per day. Overall, this translated into a $5.3 million decrease in PN charges. Actual pharmacy expenses decreased by $107,000. This quality improvement project demonstrated that implementing practice guidelines published by the American Society for Parental and Enteral Nutrition can result in quality improvement and cost savings. Clinicians with advanced certifications in nutrition support were pivotal to the success of the project.
A Simple Method of Supplementation of Omega‐3 Polyunsaturated Fatty Acids
Authors: McCowen Karen C. , Ling Pei Ra , Decker Eric , Djordjevic D. , Roberts R.F. , Coupland J.N. , Bistrian Bruce R.
Published: December 2010

Background: A relative dietary ω‐3 fatty acid deficiency exists in Western diets, and this deficiency may be associated with some chronic diseases. The aim of the present study was to supplement yogurt with docosahexaenoic acid and assess whether this fatty acid could be incorporated into plasma lipids. Methods: We developed a stable emulsion of docosahexaenoic acid that was incorporated into yogurt. Twelve healthy volunteers agreed to consume 1 serving daily that contained 600 mg of docosahexaenoic acid. Results: After 3 weeks of supplementation, plasma phospholipid docosahexaenoic acid content increased significantly, by 32%, in parallel with a 16% rise in total ω‐3 fatty acids. This result was associated with a significant 7% decline in phospholipid arachidonic acid. Conclusions: Fortification of ordinary foods with docosahexaenoic acid is a potentially attractive method of increasing ω‐3 fatty acid content of plasma lipids, and might even lower arachidonic acid concentrations.
The Macrobiotic Diet in Chronic Disease
Authors: Lerman Robert H.
Published: December 2010

The macrobiotic diet is a low‐fat, high‐fiber, high‐complex carbohydrate, mainly vegetarian diet. It is associated with a lifestyle system and a spiritual philosophy of life. Unlike many diets, the composition is not fixed and may be altered depending on a person's health status, among other considerations. Studies indicating lower serum lipid levels and blood pressure in people following a macrobiotic diet than in the general population suggest it to be an effective preventive strategy for cardiovascular disease. Many of its components suggest macrobiotics would be a valuable approach to cancer prevention. On the other hand, it has been the subject of controversy, especially with respect to its use in patients suffering from malignancies. Several remarkable anecdotal case reports have supported a therapeutic effect in patients with advanced cancers. However, to date, the few studies attempted have been inadequate to prove effectiveness and further research is warranted. Concerns include potential delay in conventional treatment for cancer, risks associated with nutrition deficiencies, and social limitations related to the complexities of strict adherence to this diet. Many aspects of currently popular dietary recommendations such as eating locally grown, in‐season, fresh, organic foods are legacies of the macrobiotic lifestyle and diet.
Search for the Optimal Diet
Authors: Mullin Gerard E.
Published: December 2010

Since the beginning of time, we have been searching for diets that satisfy our palates while simultaneously optimizing health and well‐being. Every year, there are hundreds of new diet books on the market that make a wide range of promises but rarely deliver. Unfortunately, consumers are gullible and believe much of the marketing hype because they are desperately seeking ways to maximize their health. As a result, they continue to purchase these diet books, sending many of them all the way to the bestseller list. Because many of these meal plans are not sustainable and are questionable in their approaches, the consumer is ultimately left to continue searching, only able to choose from the newest “fad” promoted by publicists rather than being grounded in science. Thus, the search for the optimal diet continues to be the “holy grail” for many of us today, presenting a challenge for nutritionists and practitioners to provide sound advice to consumers.
Nutrition Concerns and Health Effects of Vegetarian Diets
Authors: Craig Winston John
Published: December 2010

Vegetarians exhibit a wide diversity of dietary practices, often described by what is omitted from their diet. When a vegetarian diet is appropriately planned and includes fortified foods, it can be nutritionally adequate for adults and children and can promote health and lower the risk of major chronic diseases. The nutrients of concern in the diet of vegetarians include vitamin B12, vitamin D, ω‐3 fatty acids, calcium, iron, and zinc. Although a vegetarian diet can meet current recommendations for all of these nutrients, the use of supplements and fortified foods provides a useful shield against deficiency. A vegetarian diet usually provides a low intake of saturated fat and cholesterol and a high intake of dietary fiber and many health‐promoting phytochemicals. This is achieved by an increased consumption of fruits, vegetables, whole‐grains, legumes, nuts, and various soy products. As a result of these factors, vegetarians typically have lower body mass index, serum total and low‐density lipoprotein cholesterol levels, and blood pressure; reduced rates of death from ischemic heart disease; and decreased incidence of hypertension, stroke, type 2 diabetes, and certain cancers than do nonvegetarians.
Traditional Non‐Western Diets
Authors: Lipski Elizabeth
Published: December 2010

In traditional cultures, balancing health with a balanced lifestyle was a core belief. The diseases of modern civilization were rare. Indigenous people have patterns of illness very different from Western civilization; yet, they rapidly develop diseases once exposed to Western foods and lifestyles. Food and medicine were interwoven. All cultures used special or functional foods to prevent disease. Food could be used at different times either as food or medicine. Foods, cultivation, and cooking methods maximized community health and well‐being. With methods passed down through generations, cooking processes were utilized that enhanced mineral and nutrient bioavailability. This article focuses on what researchers observed about the food traditions of indigenous people, their disease patterns, the use of specific foods, and the environmental factors that affect people who still eat traditional foods.
One hundred years after Sigmund Freud’s lectures in America: towards an integration of psychoanalytic theories and techniques within psychiatry
Authors: Hoffman Leon
Published: December 2010

The impact of Sigmund Freud’s lectures in America in 1909 is discussed. Some of the roots of psychoanalysis and their contemporary relevance are addressed: neurological ideas, the discussions of the sexologists, and the degeneration theories at the turn of the twentieth century. Factors which led to the dominance of psychoanalysis in psychiatry included, in particular, its arguments against the hopelessness of degeneracy theories; yet, by isolating itself from mainstream academic psychiatry and psychology, organized psychoanalysis itself contributed to its own subsequent marginalization. In order to re-integrate itself with mainstream psychiatry, psychoanalysis needs to appreciate the importance of systematic demonstrations of the therapeutic power of psychodynamic/psychoanalytic concepts and techniques when caring for individuals.
African Firms in the Global Economy
Authors: Bigsten Arne , Söderbom Måns
Published: December 2010

In this article we review the status of African manufacturing firms in the global economy. We discuss how the policies relevant for manufacturing performance have developed over four decades starting in the 1960s, and take stock of the actual performance of the sector. We examine the prospects for improved performance, using a historical benchmark and a comparative advantage frame-work, and document empirical evidence on the relationship between openness and firm performance drawing on African firm-level data. Finally we discuss what economic policies are required to support industrial growth.
Case Studies of Internationalization in Adult and Higher Education
Authors: Coryell Joellen Elizabeth , Durodoye Beth A. , Wright Robin Redmon , Pate P. Elizabeth , Nguyen Shelbee
Published: December 2010

This report outlines a method for learning about the internationalization processes at institutions of adult and higher education and then provides the analysis of data gathered from the researchers’ own institution and from site visits to three additional universities in the United States and the United Kingdom. It was found that campus internationalization requires a deep understanding and appreciation of the institutional context. In addition, although elements of internationalization may be implemented, the findings indicate there is a need to underpin these approaches with (a) a shared understanding of what internationalization is and the ways it should ultimately impact student learning within an institution and (b) a collection of assessment methods for evaluating internationalization efforts and learning outcomes. Implications and recommendations for further research are also offered.
School, community, and family working together to address childhood obesity: Perceptions from the KOALA lifestyle intervention study
Authors: Smibert Asa , Abbott Rebecca , Macdonald Doune , Hogan Anna , Leong Gary
Published: December 2010

Epidemiological data on childhood obesity has prompted a significant response from both governments and academics seeking to recommend solutions to the reported ‘crisis’. The ‘Kinder Overweight Active Living Action’ (KOALA) healthy lifestyle programme is a randomized obesity prevention and intervention study designed to provide an understanding of how school, family, and community can work in partnership to holistically address childhood obesity. Located within the KOALA project, this paper focuses on the children’s and parents’ experiences and perceptions of the KOALA intervention and its articulation with school health and physical education (HPE). Observations on the interactions that occur between home, school, and community as key sites of intervention in childhood obesity are also unpacked. The study employed a qualitative methodology to gauge perspectives regarding the multiple sites of obesity intervention. Perspectives of children, parents, and teachers regarding the KOALA experience would suggest that there is value in planning childhood obesity interventions that link families with community programs, such as scouts, girl guides, and club sport. While long-term outcomes are yet to be ascertained, KOALA has provided scope for new possibilities in holistic approaches to healthy body weight.
Dealing with liver trauma
Authors: Leppäniemi AK
Published: December 2010

Bleeding from a traumatic liver injury often ceases spontaneously, which is the basis for non-operative management, currently used in about 80% of patients with blunt hepatic trauma. The selection of patients for non-operative management is based on the assessment of haemodynamic stability and the presence of associated organ injuries requiring surgical repair. In patients requiring surgery, definitive repair is preferred in stable patients with normal tissue perfusion and temperature, and ranges from the use of local haemostats and sutures to non-anatomic hepatic resection and direct repair of juxtahepatic venous injuries. In the most seriously injured patients with major bleeding causing severe physiological derangement, a damage control strategy including perihepatic packing is the treatment method of choice. Adjunctive procedures including hepatic angiography and embolisation are often needed in high-grade liver injuries whether undergoing surgical or non-operative management. The multidisciplinary approach also includes procedures performed for biliary complications, such as percutaneous or endoscopic drainage of bile leaks.
Sexual Orientation Differences as Deficits: Science and Stigma in the History of American Psychology
Authors: Herek Gregory M.
Published: December 2010

This article briefly describes how psychology, psychiatry, and the mental health professions (here collectively referred to as Psychology) treated sexual orientation differences as deficits for much of the 20th century, as well as some of the negative consequences that practice had for sexual minorities. The 1970s witnessed a remarkable turnaround when the American Psychiatric Association removed homosexuality from the Diagnostic and Statistical Manual of Mental Disorders and the American Psychological Association called for psychologists to work to remove the stigma historically associated with homosexuality. This history illustrates not only how cultural institutions play a central role in legitimating stigma, but also how they can recognize their own complicity in this process and work effectively to undo its harmful effects. It is argued that Psychology still has an important role to play in challenging the differences-as-deficits model in contemporary policy debates.
I’m White and You’re Not: The Value of Unraveling Ethnocentric Science
Authors: Jones James M.
Published: December 2010

Whether motivated by racist intent, ethnocentric arrogance, or data analytic myopia, research that systematically stigmatizes specific human groups is destructive. The racist assumptions of the inferiority of African culture and persons of African descent have contributed substantially to stigmatizing beliefs about African Americans. This article presents historical examples of several kinds of motivated or myopic theoretical and empirical projects that stigmatize African Americans and examples of how an examination of culture and social context may alleviate these problems. A discussion of ways to diversify psychological science includes diversifying those who do it, broadening the cultural perspectives and problems from which psychological concepts emanate (particularly in the United States), and formalizing diversity science as a system of theoretical and empirical research.
Culture and the Home-Field Disadvantage
Authors: Medin Douglas , Bennis Will , Chandler Michael
Published: December 2010

The home-field disadvantage refers to the disadvantage inherent in research that takes a particular cultural group as the starting point or standard for research, including cross-cultural research. We argue that home-field status is a serious handicap that often pushes researchers toward deficit thinking, however good the researchers' intentions may be. In this article, we aim to make this home-field bias more explicit and, in doing so, more avoidable. We discuss three often-overlooked disadvantages that result from this home-field status: the problem of marked versus unmarked culture, the problem of homogenous versus heterogeneous culture, and the problem of regression toward the mean. We also recommend four interventions researchers can apply to avoid the home-field disadvantage or, at the least, attenuate its deleterious effects.
Brain Imaging, Cognitive Processes, and Brain Networks
Authors: Gonsalves Brian D. , Cohen Neal J.
Published: December 2010

The recent, rapid expansion of the application of neuroimaging techniques to a broad variety of questions about the structure and function of mind and brain has led to much necessary and often critical introspection about what these techniques can actually tell us about cognitive processes. In this article, we attempt to place neuroimaging within the broader context of the cognitive neuroscience approach, which emphasizes the benefits of converging methodologies for understanding cognition and how it is supported by the functioning of the brain. Our arguments for what neuroimaging has to offer are supported by two specific examples from research on memory that, we believe, show how neuroimaging data have provided unique insights not only into brain organization, but also into the organization of the mind.
Bridging Psychological and Biological Science: The Good, Bad, and Ugly
Authors: Shimamura Arthur P.
Published: December 2010

Revolution or the new phrenology—the advent of functional neuroimaging has led some psychologists to address issues of structure-function relations that only two decades ago would have been relegated to science fiction. Others, however, are skeptical of recent bridges between psychological and biological science and consider these advances as misguided and leading us astray. With any new advancement comes problems and pitfalls, and constructive criticisms help to sharpen the research program. Here I offer commentary on the state of the art and identify both advances and concerns in bridging psychological and biological science.
Classification of rice (Oryza satival. japonica nipponbare) immunophilins (FKBPs, CYPs) and expression patterns under water stress
Authors: Ahn Jun Cheul , Kim Dae-Won , You Young Nim , Seok Min Sook , Park Jeong Mee , Hwang Hyunsik , Kim Beom-Gi , Luan Sheng , Park Hong-Seog , Cho Hye Sun
Published: December 2010

Background

FK506 binding proteins (FKBPs) and cyclophilins (CYPs) are abundant and ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase (PPIase) superfamily, which regulate much of metabolism through a chaperone or an isomerization of proline residues during protein folding. They are collectively referred to as immunophilin (IMM), being present in almost all cellular organs. In particular, a number of IMMs relate to environmental stresses.

Results

FKBP and CYP proteins in rice (Oryza sativa cv. Japonica) were identified and classified, and given the appropriate name for each IMM, considering the ortholog-relation with Arabidopsis and Chlamydomonas or molecular weight of the proteins. 29 FKBP and 27 CYP genes can putatively be identified in rice; among them, a number of genes can be putatively classified as orthologs of Arabidopsis IMMs. However, some genes were novel, did not match with those of Arabidopsis and Chlamydomonas, and several genes were paralogs by genetic duplication. Among 56 IMMs in rice, a significant number are regulated by salt and/or desiccation stress. In addition, their expression levels responding to the water-stress have been analyzed in different tissues, and some subcellular IMMs located by means of tagging with GFP protein.

Conclusion

Like other green photosynthetic organisms such as Arabidopsis (23 FKBPs and 29 CYPs) and Chlamydomonas (23 FKBs and 26 CYNs), rice has the highest number of IMM genes among organisms reported so far, suggesting that the numbers relate closely to photosynthesis. Classification of the putative FKBPs and CYPs in rice provides the information about their evolutional/functional significance when comparisons are drawn with the relatively well studied genera, Arabidopsis and Chlamydomonas. In addition, many of the genes upregulated by water stress offer the possibility of manipulating the stress responses in rice.
High yield expression of leptospirosis vaccine candidates LigA and LipL32 in the methylotrophic yeast Pichia pastoris
Authors: Hartwig Daiane D , Oliveira Thaís L , Seixas Fabiana K , Forster Karine M , Rizzi Caroline , Hartleben Cláudia P , McBride Alan JA , Dellagostin Odir A
Published: December 2010

Background

Leptospirosis, a zoonosis caused by Leptospira spp., is recognized as an emergent infectious disease. Due to the lack of adequate diagnostic tools, vaccines are an attractive intervention strategy. Recombinant proteins produced in Escherichia coli have demonstrated promising results, albeit with variable efficacy. Pichia pastoris is an alternative host with several advantages for the production of recombinant proteins.

Results

The vaccine candidates LigANI and LipL32 were cloned and expressed in P. pastoris as secreted proteins. Large-scale expression resulted in a yield of 276 mg/L for LigANI and 285 mg/L for LipL32. The recombinant proteins were glycosylated and were recognized by antibodies present in the sera of patients with severe leptospirosis.

Conclusions

The expression of LigANI and LipL32 in P. pastoris resulted in a significant increase in yield compared to expression in E. coli. In addition, the proteins were secreted, allowing for easy purification, and retained the antigenic characteristics of the native proteins, demonstrating their potential application as subunit vaccine candidates.
Expression of insulin-like 3 (INSL3) and differential splicing of its receptor in the ovary of rhesus macaques
Authors: Hanna Carol B , Yao Shan , Patta Maristela C , Jensen Jeffrey T , Wu Xuemei
Published: December 2010

Background

Although insulin-like 3 (INSL3) has been identified in the gonad of both sexes in many species, there are only limited reports on the distribution of INSL3 and its receptor, relaxin/insulin-like family peptide receptor 2 (RXFP2), in the primate ovary. Since the hormone-receptor pair is believed to play a role in female reproduction, investigating the transcription of INSL3/RXFP2 genes and the spatiotemporal expression of INSL3 in the nonhuman primate may shed light on the functional aspects of the system in humans.

Methods

Database mining, molecular and immunological methods were applied.

Results

One single INSL3 transcript and three novel splice variant transcripts of RXFP2 were identified in the ovary of rhesus macaques. While the full-length RXFP2 transcript is barely detectable in granulosa cells during the periovulatory period, INSL3 transcript and protein are highly abundant in theca cells surrounding antral follicles. Moreover, the INSL3 level in follicular fluid is 3-4 times higher than that in female serum which remains low throughout the menstrual cycle.

Conclusions

The presence of INSL3 and its receptor in the ovary implies a potential role of the ligand-receptor pair in female reproduction in nonhuman primates. However, the existence of multiple splice variants of RXFP2 indicates a very complex nature of the hormone-receptor system.
Immuno-Oncology biomarkers 2010 and beyond: Perspectives from the iSBTc/SITC biomarker task force
Authors: Butterfield Lisa H , Disis Mary L , Khleif Samir N , Balwit James M , Marincola Francesco M
Published: December 2010

The International Society for Biological Therapy of Cancer (iSBTc, recently renamed the Society for Immunotherapy of Cancer, SITC) hosted a one-day symposium at the National Institutes of Health on September 30, 2010 to address development and application of biomarkers in cancer immunotherapy. The symposium, titled Immuno-Oncology Biomarkers 2010 and Beyond: Perspectives from the iSBTc/SITC Biomarker Task Force, gathered approximately 230 investigators equally from academia, industry and governmental/regulatory agencies from around the globe for panel discussions and presentations on the following topics: 1) immunologic monitoring: standardization and validation of assays; 2) correlation of immunity to biologic activity, clinical response and potency assays; 3) novel methodologies for assessing the immune landscape: clinical utility of novel technologies; and 4) recommendations on incorporation of biomarkers into the clinical arena. The presentations are summarized in this report; additional program information and slides are available online at the iSBTc/SITC website.
Protection against H1N1 influenza challenge by a DNA vaccine expressing H3/H1 subtype hemagglutinin combined with MHC class II-restricted epitopes
Authors: Tan Lei , Lu Huijun , Zhang Dan , Tian Mingyao , Hu Bo , Wang Zhuoyue , Jin Ningyi
Published: December 2010

Background

Multiple subtypes of avian influenza viruses have crossed the species barrier to infect humans and have the potential to cause a pandemic. Therefore, new influenza vaccines to prevent the co-existence of multiple subtypes within a host and cross-species transmission of influenza are urgently needed.

Methods

Here we report a multi-epitope DNA vaccine targeted towards multiple subtypes of the influenza virus. The protective hemagglutinin (HA) antigens from H5/H7/H9 subtypes were screened for MHC II class-restricted epitopes overlapping with predicted B cell epitopes. We then constructed a DNA plasmid vaccine, pV-H3-EHA-H1, based on HA antigens from human influenza H3/H1 subtypes combined with the H5/H7/H9 subtype Th/B epitope box.

Results

Epitope-specific IFN-γ ELISpot responses were significantly higher in the multi-epitope DNA group than in other vaccine and control groups (P < 0.05). The multi-epitope group significantly enhanced Th2 cell responses as determined by cytokine assays. The survival rate of mice given the multi-epitope vaccine was the highest among the vaccine groups, but it was not significantly different compared to those given single antigen expressing pV-H1HA1 vaccine and dual antigen expressing pV-H3-H1 vaccine (P > 0.05). No measurable virus titers were detected in the lungs of the multi-epitope immunized group. The unique multi-epitope DNA vaccine enhanced virus-specific antibody and cellular immunity as well as conferred complete protection against lethal challenge with A/New Caledonia/20/99 (H1N1) influenza strain in mice.

Conclusions

This approach may be a promising strategy for developing a universal influenza vaccine to prevent multiple subtypes of influenza virus and to induce long-term protective immune against cross-species transmission.
Therapeutic activity of two xanthones in a xenograft murine model of human chronic lymphocytic leukemia
Authors: Loisel Séverine , Le Ster Karine , Meyer Michèle , Berthou Christian , Youinou Pierre , Kolb Jean-Pierre , Billard Christian
Published: December 2010

Background

We previously reported that allanxanthone C and macluraxanthone, two xanthones purified from Guttiferae trees, display in vitro antiproliferative and proapoptotic activities in leukemic cells from chronic lymphocytic leukemia (CLL) and leukemia B cell lines.

Results

Here, we investigated the in vivo therapeutic effects of the two xanthones in a xenograft murine model of human CLL, developed by engrafting CD5-transfected chronic leukemia B cells into SCID mice. Treatment of the animals with five daily injections of either allanxanthone C or macluraxanthone resulted in a significant prolongation of their survival as compared to control animals injected with the solvent alone (p = 0.0006 and p = 0.0141, respectively). The same treatment of mice which were not xenografted induced no mortality.

Conclusion

These data show for the first time the in vivo antileukemic activities of two plant-derived xanthones, and confirm their potential interest for CLL therapy.
Phase III Comparison of Prophylactic Cranial Irradiation Versus Observation in Patients With Locally Advanced Non–Small-Cell Lung Cancer: Primary Analysis of Radiation Therapy Oncology Group Study RTOG 0214
Authors: Gore Elizabeth M. , Bae Kyounghwa , Wong Stuart J. , Sun Alexander , Bonner James A. , Schild Steven E. , Gaspar Laurie E. , Bogart Jeffery A. , Werner-Wasik Maria , Choy Hak
Published: December 2010

Purpose

This study was conducted to determine if prophylactic cranial irradiation (PCI) improves survival in locally advanced non–small-cell lung cancer (LA-NSCLC).

Patients and Methods

Patients with stage III NSCLC without disease progression after treatment with surgery and/or radiation therapy (RT) with or without chemotherapy were eligible. Participants were stratified by stage (IIIA v IIIB), histology (nonsquamous v squamous), and therapy (surgery v none) and were randomly assigned to PCI or observation. PCI was delivered to 30 Gy in 15 fractions. The primary end point of the study was overall survival (OS). Secondary end points were disease-free survival (DFS), neurocognitive function (NCF), and quality of life. Kaplan-Meier and log-rank analyses were used for OS and DFS. The incidence of brain metastasis (BM) was evaluated with the logistic regression model.

Results

Overall, 356 patients were accrued of the targeted 1,058. The study was closed early because of slow accrual; 340 of the 356 patients were eligible. The 1-year OS (P = .86; 75.6% v 76.9% for PCI v observation) and 1-year DFS (P = .11; 56.4% v 51.2% for PCI v observation) were not significantly different. The hazard ratio for observation versus PCI was 1.03 (95% CI, 0.77 to 1.36). The 1-year rates of BM were significantly different (P = .004; 7.7% v 18.0% for PCI v observation). Patients in the observation arm were 2.52 times more likely to develop BM than those in the PCI arm (unadjusted odds ratio, 2.52; 95% CI, 1.32 to 4.80).

Conclusion

In patients with stage III disease without progression of disease after therapy, PCI decreased the rate of BM but did not improve OS or DFS.
New Media Scholarship and Teaching
Authors: Cushman Ellen
Published: December 2010

This article describes the culture of some English departments and the value system often attached to various forms of media in them. Because English studies so often values the letter, texts, and the consumption of these, it's been caught in its own hierarchy of signs. English studies has been slow to create new media scholarship and train future teachers to understand multiple media despite challenges from within and outside of the discipline to do so. Samples of new media scholarship are offered to demonstrate the plurality of scholarship and teaching practices possible with new media.
The origin and identity of embryonic stem cells
Authors: Nichols Jennifer , Smith Austin
Published: December 2010

Embryonic stem (ES) cells are used extensively in biomedical research and as a model with which to study early mammalian development, but their exact origin has been subject to much debate. They are routinely derived from pre-implantation embryos, but it has been suggested that the cells that give rise to ES cells might arise from epiblast cells that are already predisposed to a primordial germ cell (PGC) fate, which then progress to ES cell status via the PGC lineage. Based on recent findings, we propose here that ES cells can be derived directly from early epiblast cells and that ES cells might arise via two different routes that are dictated by their culture conditions.
Retinoic acid stimulates myocardial expansion by induction of hepatic erythropoietin which activates epicardialIgf2
Authors: Brade Thomas , Kumar Sandeep , Cunningham Thomas J. , Chatzi Christina , Zhao Xianling , Cavallero Susana , Li Peng , Sucov Henry M. , Ruiz-Lozano Pilar , Duester Gregg
Published: December 2010

Epicardial signaling and Rxra are required for expansion of the ventricular myocardial compact zone. Here, we examine Raldh2–/– and Rxra–/– mouse embryos to investigate the role of retinoic acid (RA) signaling in this developmental process. The heart phenotypes of Raldh2 and Rxra mutants are very similar and are characterized by a prominent defect in ventricular compact zone growth. Although RA activity is completely lost in Raldh2–/– epicardium and the adjacent myocardium, RA activity is not lost in Rxra–/– hearts, suggesting that RA signaling in the epicardium/myocardium is not required for myocardial compact zone formation. We explored the possibility that RA-mediated target gene transcription in non-cardiac tissues is required for this process. We found that hepatic expression of erythropoietin (EPO), a secreted factor implicated in myocardial expansion, is dependent on both Raldh2 and Rxra. Chromatin immunoprecipitation studies support Epo as a direct target of RA signaling in embryonic liver. Treatment of an epicardial cell line with EPO, but not RA, upregulates Igf2. Furthermore, both Raldh2–/– and Rxra–/– hearts exhibit downregulation of Igf2 mRNA in the epicardium. EPO treatment of cultured Raldh2–/– hearts restores epicardial Igf2 expression and rescues ventricular cardiomyocyte proliferation. We propose a new model for the mechanism of RA-mediated myocardial expansion in which RA directly induces hepatic Epo resulting in activation of epicardial Igf2 that stimulates compact zone growth. This RA-EPO-IGF2 signaling axis coordinates liver hematopoiesis with heart development.
A mouse model for monitoring islet cell genesis and developing therapies for diabetes
Authors: Shimajiri Yoshinori , Kosaka Yasuhiro , Scheel David W. , Lynn Francis C. , Kishimoto Nina , Wang Juehu , Zhao Shuhong , German Michael S.
Published: December 2010

Transient expression of the transcription factor neurogenin-3 marks progenitor cells in the pancreas as they differentiate into islet cells. We developed a transgenic mouse line in which the surrogate markers secreted alkaline phosphatase (SeAP) and enhanced green florescent protein (EGFP) can be used to monitor neurogenin-3 expression, and thus islet cell genesis. In transgenic embryos, cells expressing EGFP lined the pancreatic ducts. SeAP was readily detectable in embryos, in the media of cultured embryonic pancreases and in the serum of adult animals. Treatment with the γ-secretase inhibitor DAPT, which blocks Notch signaling, enhanced SeAP secretion rates and increased the number of EGFP-expressing cells as assayed by fluorescence-activated cell sorting (FACS) and immunohistochemistry in cultured pancreases from embryos at embryonic day 11.5, but not in pancreases harvested 1 day later. By contrast, treatment with growth differentiation factor 11 (GDF11) reduced SeAP secretion rates. In adult mice, partial pancreatectomy decreased, whereas duct ligation increased, circulating SeAP levels. This model will be useful for studying signals involved in islet cell genesis in vivo and developing therapies that induce this process.
Impaired remodeling phase of fracture repair in the absence of matrix metalloproteinase-2
Authors: Lieu Shirley , Hansen Erik , Dedini Russell , Behonick Danielle , Werb Zena , Miclau Theodore , Marcucio Ralph , Colnot Céline
Published: December 2010

The matrix metalloproteinase (MMP) family of extracellular proteases performs crucial roles in development and repair of the skeleton owing to their ability to remodel the extracellular matrix (ECM) and release bioactive molecules. Most MMP-null skeletal phenotypes that have been previously described are mild, thus permitting the assessment of their functions during bone repair in the adult. In humans and mice, MMP2 deficiency causes a musculoskeletal phenotype. In this study, we assessed the role of MMP2 during mouse fracture repair and compared it with the roles of MMP9 and MMP13. Mmp2 was expressed at low levels in the normal skeleton and was broadly expressed in the fracture callus. Treatment of wild-type mice with a general MMP inhibitor, GM6001, caused delayed cartilage remodeling and bone formation during fracture repair, which resembles the defect observed in Mmp9–/– mice. Unlike Mmp9- and Mmp13-null mutations, which affect both cartilage and bone in the callus, the Mmp2-null mutation delayed bone remodeling but not cartilage remodeling. This remodeling defect occurred without changes in either osteoclast recruitment or vascular invasion of the fracture callus compared with wild type. However, we did not detect changes in expression of Mmp9, Mmp13 or Mt1-Mmp (Mmp14) in the calluses of Mmp2-null mice compared with wild type by in situ hybridization, but we observed decreased expression of Timp2 in the calluses of Mmp2-, Mmp9- and Mmp13-null mice. In keeping with the skeletal phenotype of Mmp2-null mice, MMP2 plays a role in the remodeling of new bone within the fracture callus and impacts later stages of bone repair compared with MMP9 and MMP13. Taken together, our results indicate that MMPs play unique and distinct roles in regulating skeletal tissue deposition and remodeling during fracture repair.