bluuebunny/crossref_metadata_2025 huggingface dataset:
Best Practice Environmental Impact Assessment: A Model Framework for Australia
Authors: Macintosh Andrew
Published: December 2010

Environmental impact assessment (EIA) is a process that involves the identification, prediction, evaluation and mitigation of the environmental and other impacts associated with development proposals and policies, plans and programs. Australian governments were amongst the first in the world to introduce EIA in the 1970s. Since then, the federal, state and territory EIA regimes have undergone multiple changes. In recent times, the push for EIA reform has intensified as governments have sought ways to improve the cost‐effectiveness of regulatory processes. In light of the impetus for change, this article outlines principles and a framework for best practice EIA in Australia. The intention is to inform the policy development processes at the federal, state and local levels.
To the Ends of the Earth? Minority Biblical Criticism in Motion – They were All Together in One Place? Toward Minority Biblical Criticism – Edited by Randall C. Bailey, Tat‐siong Benny Liew, and Fernando F. Segovia
Authors: Kim Uriah Y.
Published: December 2010

What is minority biblical criticism? Why do all biblical scholars need to engage with it? Do race and ethnicity, sex and gender, and political and socio‐economic concerns matter in interpreting the Bible? Leading minority scholars of the Bible from African American, Asian American, and Latino/a American communities come together to answer these questions and break grounds for further cooperation and development of this much‐needed hermeneutical strategy. The authors in this volume willfully disobey the rules of objectivity and universality and shatter the pretension of those who claim that one's context has no bearing on their interpretation of the text. They push the boundaries of the discipline of biblical studies and take the interdisciplinary turn in order to create a space in which minority biblical criticism can stand on its own.
Two Unities of Consciousness
Authors: Schechter Elizabeth
Published: December 2010

Abstract: This paper argues for a distinction between possession of a unified consciousness and possession of a single stream of consciousness. Although the distinction has widespread applicability in discussions of the structure of consciousness and of pathologies of conscious experience, I will illustrate its importance primarily using the debate about consciousness in split‐brain subjects, suggesting that those who have argued that split‐brain subjects have two streams of consciousness apiece and those who have argued that they have a unified consciousness may both be right.
A New Fundamental Freedom beyond Market Integration: Union Citizenship and its Dynamics for Shifting the Economic Paradigm of European Integration
Authors: Wollenschläger Ferdinand
Published: December 2010

The development of European integration from an economic to a political community has become manifest not just in the continuous addition of non‐economic policy areas to the treaties. The introduction of Union citizenship (and its controversial subsequent development in the European Court of Justice's jurisprudence) has also triggered a paradigm shift in one of the community's core areas, the concept of negative integration hitherto intrinsically linked to the internal market. Thus, neither the individual's quality as a market actor nor his/her involvement in a transnational economic activity is a condition for enjoyment of the market freedoms' core guarantees, these being a right of residence and a far‐reaching claim to national treatment in other Member States, as well as a prohibition on restrictions to the free movement of persons. A new fundamental freedom beyond market integration (‘Grundfreiheit ohne Markt’) has emerged. This process, whose consequences for the welfare systems of the wealthier Member States have been fiercely discussed for some time, however, also threatens to curtail severely the regulatory autonomy at the national level.
Pathologies of Deliberation in the EU
Authors: Karolewski Ireneusz Pawel
Published: December 2010

The article explores the ‘dark side’ of deliberation with regard to the EU. In contrast to the dominant apologetics of deliberation, it argues that even though deliberation might have benevolent effects on decision making in the EU, the convention method cannot be viewed as a democratic alternative to the intergovernmental conferences. This is due to the pathologies of deliberation that can only be corrected by applying additional mechanisms. The article explores the pathologies of deliberation by referring to recent experience with the convention method applied within the Convention on the Charter of Fundamental Rights (1999/2000) and the Convention on the Future of the European Union (2002/2003). It discusses two types of deliberative pathologies including the false will‐formation and the rational hijacking of deliberation which question the validity of democratic claims made by deliberation theory.
Pluralism, Deference and the Margin of Appreciation Doctrine
Authors: Gerards Janneke
Published: December 2010

In this article it will be argued that good use of the instrument of deference might help the EU courts to deal with the situation of pluralism that is currently visible in the European legal order. By means of deferential judicial review, the EU courts can pay due respect to national constitutional traditions and to national legislative and policy choices, thus preventing situations of real conflict. In addition, deference enables the EU courts to take into account the intricacies related to judicial review of norms drafted by co‐equal institutions or by national elected bodies. Although the EU courts already make use of some form of deferential review, they may use the instrument in a clearer and more structured manner. As a basis for the development of a European ‘doctrine of deference’, a comparison will be made with the margin of appreciation doctrine devised by the European Court of Human Rights. Although this doctrine is certainly not fault‐free, it offers a number of advantages in terms of clarity and controllability. If improved and adapted on the basis of theoretical notions of procedural democracy, the doctrine might be put to good use by the EU courts.
Coexisting problem behaviour in severe dyslexia
Authors: Dahle Anne Elisabeth , Knivsberg Ann‐Mari , Andreassen Anne Brit
Published: December 2010

A small group of children and young adolescent with dyslexia has severely impaired reading skills despite prolonged special education. These are the students in focus. In dyslexia, problem behaviour, internalised as well as externalised, has previously been reported, so also for the participants with dyslexia in this study. The aim of the present study was to obtain more in‐depth knowledge of the behaviour problems from various informants, representing different settings. This kind of information is imperative for identifying problem behaviour, and for planning and implementing remedial programmes. A clinical group of 70 students with severe dyslexia, due to phonological problems, and a control group of 70 without reading problems participated. The two groups were pair‐wise matched on age, gender, cognitive level and whether they lived in rural or urban areas. Mean age was 150 months, and mean IQ was approximately 100 in both groups. Parents, teachers and participants provided information on behaviour through the Achenbach questionnaires Child Behavior Checklist, Teacher's Report Form and Youth Self Report. Behaviour is, in these questionnaires, divided into eight syndrome areas called Withdrawn, Somatic Complaints, Anxious/Depressed, Social Problems, Thought Problems, Attention Problems, Delinquent Behavior and Aggressive Behavior. The three informant groups reported significantly more problems in the dyslexia group than in the controls in all the syndrome areas. Parents reported more children with dyslexia to be anxious and depressed, and have social problems and attention problems than teachers. They also reported suicidal ideations in nine participants with dyslexia. In addition, parents rated more internalising and total problems in the dyslexia group than teachers.
Effects of neuroinflammation on the regenerative capacity of brain stem cells
Authors: Russo Isabella , Barlati Sergio , Bosetti Francesca
Published: December 2010

J. Neurochem. (2011) 116, 947–956.

In the adult brain, neurogenesis under physiological conditions occurs in the subventricular zone and in the dentate gyrus. Although the exact molecular mechanisms that regulate neural stem cell proliferation and differentiation are largely unknown, several factors have been shown to affect neurogenesis. Decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age‐related brain dysfunction. Furthermore, in pathological conditions of the central nervous system associated with neuroinflammation, inflammatory mediators such as cytokines and chemokines can affect the capacity of brain stem cells and alter neurogenesis. In this review, we summarize the state of the art on the effects of neuroinflammation on adult neurogenesis and discuss the use of the lipopolysaccharide‐model to study the effects of inflammation and reactive‐microglia on brain stem cells and neurogenesis. Furthermore, we discuss the possible causes underlying reduced neurogenesis with normal aging and potential anti‐inflammatory, pro‐neurogenic interventions aimed at improving memory deficits in normal and pathological aging and in neurodegenerative diseases.
Synthesis of novel tetracationic asymmetric monomeric monomethine cyanine dyes – highly fluorescent dsDNA probes
Authors: Vasilev Aleksey , Deligeorgiev Todor , Kaloyanova Stefka , Stoyanov Stanimir , Maximova Vera , Vaquero Juan J , Alvarez‐Builla Julio
Published: December 2010

Quaternisation of monomethine cyanine dyes bearing haloalkyl chains, with the appropriate monoquaternised 1,4‐diazabicyclo[2.2.2]octane derivatives, yielded novel tetracationic asymmetric monomeric monomethine cyanine dyes belonging to the thiazole orange family. The optimal conditions for this reaction were investigated. The longest wavelength absorption maxima of the studied dyes are in the region 504–507 nm. The molar absorptivities of the target dyes are high, with values between 70 500 and 99 500 l mol−1 cm−1. The fluorescence intensity and the fluorescence quantum yields of the free dyes in solution or in the presence of double‐stranded DNA were determined using thiazole orange for comparison. The dyes are suitable for nucleic acid detection and have a high binding affinity, attributable to their four positive charges.
Discovery of the Drosophila (Drosophila) robusta species group (Diptera, Drosophilidae) from Southeast Asian tropics, with the descriptions of six new species
Authors: SUWITO Awit , WATABE Hideaki
Published: December 2010

Six new species of the Drosophila robusta species group are described from Southeast Asian Islands. Kalimantan and Sunda Islands lie east of Bali, from which Drosophila barobusta sp.nov and D. uncinata sp.nov belong to the lacertosa subgroup, and D. sungaicola sp.nov, D. baliensis sp.nov, D. hitam sp.nov and D. subaquatica sp.nov to the okadai subgroup. The robusta group from Southeast Asian tropics exclusively inhabits streamsides in mountainous highlands with an elevation of more than 600 m from the sea level.
Neck and Scleral Hemorrhage in Drowning*
Authors: Alexander Russell T. , Jentzen Jeffrey M.
Published: December 2010

Abstract:  The determination of the cause and manner of death for a body recovered from the water can be difficult because of a lack of autopsy findings specific for drowning. This case report describes a 30‐year‐old man found submerged at the bottom of a hotel pool. An autopsy revealed scleral hemorrhages and fascial hemorrhages of multiple muscles of the anterior and posterior neck bilaterally. No evidence of traumatic injury was on the surface of the body. An investigation by law enforcement found no evidence of foul play. The occurrence of petechial and neck hemorrhage in a body recovered from the water is controversial, and a review of this literature will be given. We suggest that fascial hemorrhages of the muscles of the neck, as well as cephalic hemorrhages, can be explained by drowning‐related elevated central venous pressure that is communicated to the head through the valveless veins of the neck.
Preliminary Radiological Assessment of Age‐related Change in the Trabecular Structure of the HumanOs Pubis*
Authors: Wade Andrew , Nelson Andrew , Garvin Greg , Holdsworth David W.
Published: December 2010

Abstract: This preliminary study examines correlations between age‐at‐death and changes in the trabecular architecture of the humanos pubis,utilizing continuous, quantitative data from plain film radiography, computed tomography (CT), and micro‐CT scans of 65 male innominates. Radiography provides nondestructive options for assessment, digital preservation, and presentation of human skeletal remains; important for forensic and culturally sensitive archaeological materials, which must remain unmodified for opposing experts, future researchers, or repatriation and reburial. Radiographic techniques permit analysis of remains that cannot be disarticulated (e.g., religious proscription, mummies), and trabecular measures provide data where traditional surface indicators are obscured or damaged. Potentially, robust predictive models derived herein achieveR‐values of 0.522, 0.447, and 0.731, respectively. Further testing of these methods may validate these techniques as further lines of evidence in age estimation, with the potential to improve on the accuracy of traditional qualitative techniques by providing quantitative, continuous variables in predicting skeletal age‐at‐death.
Macroscopic Observations of the Effects of Varying Fresh Water pH on Bone
Authors: Christensen Angi M. , Myers Sarah W.
Published: December 2010

Abstract:  Little is known about the decomposition of remains in aquatic environments of varying pH, and even less is known about the specific effects of these environments on bone. Bovine bones were placed in solutions of pH 1, 4, 7, 10, and 14 and observed over a period of 1 year. All solutions eventually removed or dissolved the soft tissues from the external surface of the bone. The pH 7 and pH 10 solutions had little effect on the bone, but the other solutions affected the bone to varying degrees. Extreme pH levels were the most destructive, while more moderate pH levels had lesser but significant and interesting effects. Empirical data on postmortem aquatic changes may be extremely useful in forensic contexts for both improving time since death estimates and also for providing better information to underwater recovery experts thereby potentially increasing the quantity and quality of remains recovery.
Study of the osseointegration of dental implants placed with an adapted surgical technique
Authors: Al‐Marshood Maysa M. , Junker Rudiger , Al‐Rasheed Abdulaziz , Al Farraj Aldosari Abdullah , Jansen John A. , Anil Sukumaran
Published: December 2010

Objective: To study the osseointegration of dental implants placed with a modified surgical technique in Beagle dogs and to compare it with the conventional method.

Materials and methods: Dental implants were placed bilaterally in the mandible of Beagle dogs using the press‐fit as well as undersized implant bed preparation technique. Micro computer tomography (micro‐CT) and histometric methods were used to analyze the bone implant contact and bone volume (BV) around the implants.

Results: The bone‐to‐implant contact percentage (BIC: expressed as %), first BIC (1st BIC: expressed in mm), sulcus depth (SD: expressed in mm) and connective tissue thickness (CT: expressed in mm) were analyzed for both groups. The BIC percentage was significantly higher for the undersized installed implants (P=0.0118). Also, a significant difference existed between the undersized and press‐fit installed implants for the first screw thread showing bone contact (P=0.0145). There were no significant differences in mucosal response (SD and CT) for both installation procedures. Also, no significant difference was found in the BV, as measured using micro‐CT, between the implants placed with an undersized technique (59.3±4.6) compared with the press‐fit implants (56.6±4.3).

Conclusion: From the observations of the study, it can be concluded that an undersized implant bed can enhance the implant–bone response.

To cite this article:
 Al‐Marshood MM, Junker R, Al‐Rasheed A, Al Farraj Aldosari A, Jansen JA, Anil S. Study of the osseointegration of dental implants placed with an adapted surgical technique Clin. Oral Impl. Res. 22, 2011; 753–759 doi: 10.1111/j.1600‐0501.2010.02055.x
Immunization delivered by lentiviral vectors for cancer and infectious diseases
Authors: Hu Biliang , Tai April , Wang Pin
Published: December 2010

Summary:  The increasing level of understanding of the lentivirus biology has been instrumental in shaping the design strategy of creating therapeutic lentiviral delivery vectors. As a result, lentiviral vectors have become one of the most powerful gene transfer vehicles. They are widely used for therapeutic purposes as well as in studies of basic biology, due to their unique characteristics. Lentiviral vectors have been successfully employed to mediate durable and efficient antigen expression and presentation in dendritic cells both in vitro and in vivo, leading to the activation of cellular immunity and humoral responses. This capability makes the lentiviral vector an ideal choice for immunizations that target a wide range of cancers and infectious diseases. Further advances into optimizing the vector system and understanding the relationship between the immune system and diseases pathogenesis will only augment the potential benefits and utility of lentiviral vaccines for human health.
Living in a house of cards: re‐evaluating CD8+ T‐cell immune correlates against HIV
Authors: Makedonas George , Betts Michael R.
Published: December 2010

Summary:  The Merck STEP and the Thai RV144 human immunodeficiency virus (HIV) vaccine trials confirmed that we still have a long way to go before developing a prophylactic HIV vaccine. The main issue at hand is that we have yet to identify an immunological correlate of protection against HIV. While many question the T‐cell‐based approach towards vaccine development, it is likely that T cells will be a necessary part of any vaccine strategy. CD8+ T cells remain an attractive option because of their ability to specifically recognize and eliminate virally infected host cells. In this review, we recapitulate the evidence for CD8+ T cells as an immunological correlate against HIV, but more importantly, we assess the means by which we evaluate their antiviral capacity. To achieve a breakthrough in the domain of T‐cell‐based HIV vaccine development, it has become abundantly clear that we must overhaul our system of immune monitoring and come up with a ‘rational’ tactic to evaluate the efficacy of HIV‐specific CD8+ T cells.
Progress and novel strategies in vaccine development and treatment of anthrax
Authors: Chitlaru Theodor , Altboum Zeev , Reuveny Shaul , Shafferman Avigdor
Published: December 2010

Summary:  The lethal anthrax disease is caused by spores of the Gram‐positive Bacillus anthracis, a member of the cereus group of bacilli. Although the disease is very rare in the Western world, development of anthrax countermeasures gains increasing attention due to the potential use of B. anthracis spores as a bio‐terror weapon. Protective antigen (PA), the non‐toxic subunit of the bacterial secreted exotoxin, fulfills the role of recognizing a specific receptor and mediating the entry of the toxin into the host target cells. PA elicits a protective immune response and represents the basis for all current anthrax vaccines. Anti‐PA neutralizing antibodies are useful correlates for protection and for vaccine efficacy evaluation. Post exposure anti‐toxemic and anti‐bacteremic prophylactic treatment of anthrax requires prolonged antibiotic administration. Shorter efficient postexposure treatments may require active or passive immunization, in addition to antibiotics. Although anthrax is acknowledged as a toxinogenic disease, additional factors, other than the bacterial toxin, may be involved in the virulence of B. anthracis and may be needed for the long‐lasting protection conferred by PA immunization. The search for such novel factors is the focus of several high throughput genomic and proteomic studies that are already leading to identification of novel targets for therapeutics, for vaccine candidates, as well as biomarkers for detection and diagnosis.
Immunology of gut mucosal vaccines
Authors: Pasetti Marcela F. , Simon Jakub K. , Sztein Marcelo B. , Levine Myron M.
Published: December 2010

Summary:  Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross‐talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell‐mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines.
Immunogenomics and systems biology of vaccines
Authors: Buonaguro Luigi , Pulendran Bali
Published: December 2010

Summary:  Vaccines represent a potent tool to prevent or contain infectious diseases with high morbidity or mortality. However, despite their widespread use, we still have a limited understanding of the mechanisms underlying the effective elicitation of protective immune responses by vaccines. Recent research suggests that this represents the cooperative action of the innate and adaptive immune systems. Immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules, whose list is constantly updated to fill the several empty spaces of this puzzle. The recent development of new technologies and computational tools permits the comprehensive and quantitative analysis of the interactions between all of the components of immunity over time. Here, we review the role of the innate immunity in the host response to vaccine antigens and the potential of systems biology in providing relevant and novel insights in the mechanisms of action of vaccines to improve their design and effectiveness.
Biological challenges and technological opportunities for respiratory syncytial virus vaccine development
Authors: Graham Barney S.
Published: December 2010

Summary:  Respiratory syncytial virus (RSV) is an important cause of respiratory disease causing high rates of hospitalizations in infants, significant morbidity in children and adults, and excess mortality in the elderly. Major barriers to vaccine development include early age of RSV infection, capacity of RSV to evade innate immunity, failure of RSV‐induced adaptive immunity to prevent reinfection, history of RSV vaccine‐enhanced disease, and lack of an animal model fully permissive to human RSV infection. These biological challenges, safety concerns, and practical issues have significantly prolonged the RSV vaccine development process. One great advantage compared to other difficult viral vaccine targets is that passively administered neutralizing monoclonal antibody is known to protect infants from severe RSV disease. Therefore, the immunological goals for vaccine development are to induce effective neutralizing antibody to prevent infection and to avoid inducing T‐cell response patterns associated with enhanced disease. Live‐attenuated RSV and replication‐competent chimeric viruses are in advanced clinical trials. Gene‐based strategies, which can control the specificity and phenotypic properties of RSV‐specific T‐cell responses utilizing replication‐defective vectors and which may improve on immunity from natural infection, are progressing through preclinical testing. Atomic level structural information on RSV envelope glycoproteins in complex with neutralizing antibodies is guiding design of new vaccine antigens that may be able to elicit RSV‐specific antibody responses without induction of RSV‐specific T‐cell responses. These new technologies may allow development of vaccines that can protect against RSV‐mediated disease in infants and establish a new immunological paradigm in the host to achieve more durable protection against reinfection.
From optical bench to cageside: intravital microscopy on the long road to rational vaccine design
Authors: Hickman Heather D. , Bennink Jack R. , Yewdell Jonathan W.
Published: December 2010

Summary:  No antiviral vaccine is perfect. For some important pathogens, there are no effective vaccines. Many current vaccines are based on the working principles of Jenner and Pasteur, that is, empiric administration of attenuated or inactivated forms of the pathogen. Tapping the full potential of vaccination requires a thorough understanding of the mechanism of immune activation by pathogens and their individual components. Though the rate of discovery continues to accelerate, the complexity of the immune system is daunting, particularly when integrated into the overall physiology of the host. Here, we review the application of multiphoton microscopy to examine host‐pathogen interactions, focusing on our recent efforts to understand mouse CD8+ T‐cell responses to viruses at the level of cellular interactions in lymph nodes draining the infection site. We also discuss our recent efforts to understand the influence of the sympathetic nervous system on antiviral immunity, with the ultimate goal of appreciating the traditional elements of immunity as just one facet of the total organismal response to infection and immunization.
Smallpox vaccines: targets of protective immunity
Authors: Moss Bernard
Published: December 2010

Summary:  The eradication of smallpox, one of the great triumphs of medicine, was accomplished through the prophylactic administration of live vaccinia virus, a comparatively benign relative of variola virus, the causative agent of smallpox. Nevertheless, recent fears that variola virus may be used as a biological weapon together with the present susceptibility of unimmunized populations have spurred the development of new‐generation vaccines that are safer than the original and can be produced by modern methods. Predicting the efficacy of such vaccines in the absence of human smallpox, however, depends on understanding the correlates of protection. This review outlines the biology of poxviruses with particular relevance to vaccine development, describes protein targets of humoral and cellular immunity, compares animal models of orthopoxvirus disease with human smallpox, and considers the status of second‐ and third‐generation smallpox vaccines.
Vaccines to combat the neglected tropical diseases
Authors: Bethony Jeffrey M. , Cole Rhea N. , Guo Xiaoti , Kamhawi Shaden , Lightowlers Marshall W. , Loukas Alex , Petri William , Reed Steven , Valenzuela Jesus G. , Hotez Peter J.
Published: December 2010

Summary:  The neglected tropical diseases (NTDs) represent a group of parasitic and related infectious diseases such as amebiasis, Chagas disease, cysticercosis, echinococcosis, hookworm, leishmaniasis, and schistosomiasis. Together, these conditions are considered the most common infections in low‐ and middle‐income countries, where they produce a level of global disability and human suffering equivalent to better known conditions such as human immunodeficiency virus/acquired immunodeficiency syndrome and malaria. Despite their global public health importance, progress on developing vaccines for NTD pathogens has lagged because of some key technical hurdles and the fact that these infections occur almost exclusively in the world’s poorest people living below the World Bank poverty line. In the absence of financial incentives for new products, the multinational pharmaceutical companies have not embarked on substantive research and development programs for the neglected tropical disease vaccines. Here, we review the current status of scientific and technical progress in the development of new neglected tropical disease vaccines, highlighting the successes that have been achieved (cysticercosis and echinococcosis) and identifying the challenges and opportunities for development of new vaccines for NTDs. Also highlighted are the contributions being made by non‐profit product development partnerships that are working to overcome some of the economic challenges in vaccine manufacture, clinical testing, and global access.
Prospects for prophylactic and therapeutic vaccines against the hepatitis C viruses
Authors: Houghton Michael
Published: December 2010

Summary:  Encouraging efficacy data have been obtained in the hepatitis C virus (HCV) chimpanzee model using prophylactic vaccines comprising adjuvanted recombinant envelope gpE1/gpE2 glycoproteins or prime/boost immunization regimens using defective adenoviruses and plasmid DNA expressing non‐structural genes. While usually not resulting in sterilizing immunity after experimental challenge, the progression to chronic, persistent infection (which is responsible for HCV‐associated pathogenicity in human) is inhibited. These and other vaccine candidates are in clinical development for both prophylactic as well as possible therapeutic applications. Given that other vaccines tested in the chimpanzee model may be possibly increasing the rate of chronicity, it is very important that this model continues to be available and used prior to initiation of clinical development. Several vaccine monotherapy trials in chronically infected HCV patients are resulting in small declines in viral load, suggesting that in future, combining vaccination with antiviral drug treatment may be beneficial.
Use of defined TLR ligands as adjuvants within human vaccines
Authors: Duthie Malcolm S. , Windish Hillarie Plessner , Fox Christopher B. , Reed Steven G.
Published: December 2010

Summary:  Our improved understanding of how innate immune responses can be initiated and how they can shape adaptive B‐ and T‐cell responses is having a significant impact on vaccine development by directing the development of defined adjuvants. Experience with first generation vaccines, as well as rapid advances in developing defined vaccines containing Toll‐like receptor ligands (TLRLs), indicate that an expanded number of safe and effective vaccines containing such molecules will be available in the future. In this review, we outline current knowledge regarding TLRs, detailing the different cell types that express TLRs, the various signaling pathways TLRs utilize, and the currently known TLRLs. We then discuss the current status of TLRLs within vaccine development programs, including the importance of appropriate formulation, and how recent developments can be used to better define the mechanisms of action of vaccines. Finally, we introduce the possibility of using TLRLs, either in combination or with non‐TLRLs, to synergistically potentiate vaccine‐induced responses to provide not only prophylactic, but therapeutic protection against infectious diseases and cancer.
DNA vaccines: an historical perspective and view to the future
Authors: Liu Margaret A.
Published: December 2010

Summary: This review provides a detailed look at the attributes and immunologic mechanisms of plasmid DNA vaccines and their utility as laboratory tools as well as potential human vaccines. The immunogenicity and efficacy of DNA vaccines in a variety of preclinical models is used to illustrate how they differ from traditional vaccines in novel ways due to thein situantigen production and the ease with which they are constructed. The ability to make new DNA vaccines without needing to handle a virulent pathogen or to adapt the pathogen for manufacturing purposes demonstrates the potential value of this vaccine technology for use against emerging and epidemic pathogens. Similarly, personalized anti‐tumor DNA vaccines can also readily be made from a biopsy. Because DNA vaccines bias the T‐helper (Th) cell response to a Th1 phenotype, DNA vaccines are also under development for vaccines against allergy and autoimmune diseases. The licensure of four animal health products, including two prophylactic vaccines against infectious diseases, one immunotherapy for cancer, and one gene therapy delivery of a hormone for a food animal, provides evidence of the efficacy of DNA vaccines in multiple species including horses and pigs. The size of these target animals provides evidence that the somewhat disappointing immunogenicity of DNA vaccines in a number of human clinical trials is not due simply to the larger mass of humans compared with most laboratory animals. The insights gained from the mechanisms of protection in the animal vaccines, the advances in the delivery and expression technologies for increasing the potency of DNA vaccines, and encouragingly potent human immune responses in certain clinical trials, provide insights for future efforts to develop DNA vaccines into a broadly useful vaccine and immunotherapy platform with applications for human and animal health.
The effectiveness of systemic eradication therapy against oral Helicobacter pylori
Authors: Bago Ivona , Bago Josip , Plečko Vanda , Aurer Andrej , Majstorović Karolina , Budimir Ana
Published: December 2010

J Oral Pathol Med (2010) 40: 428–432

Background:  Helicobacter pylori infection is associated with numerous gastroduodenal diseases. The oral cavity could be a potential extragastric reservoir for H. pylori, and oral H. pylori might cause gastric reinfection after the eradication therapy. The aim of the study was to evaluate the presence of H. pylori in oral cavity of patients with gastric H. pylori infection and to examine the effectiveness of the eradication therapy against H. pylori in stomach and in the oral cavity.

Methods:  Fifty‐six patients with chronic periodontitis and gastric H. pylori were enrolled in the study. Gastric H. pylori infection was determined using 13C‐urea breath test before and 3 months after eradication therapy. The presence of the oral H. pylori was assessed using polymerase chain reaction before and 3 months after eradication therapy. The 1‐week eradication therapy consisted of amoxycilin 1 g, clarithromycin 500 mg, and proton pump inhibitor 20 mg twice a day.

Results:  Of 56 subjects with gastric infection, 23 (41.1%) harbored H. pylori in the oral cavity. Eradication rate in stomach was 78.3%, whereas in the oral cavity, H. pylori was not detected from any sample after the eradication therapy.

Conclusion:  Almost half of the patients with gastric H. pylori harbored the bacterium in the oral cavity. After the eradication therapy, H. pylori was not detected in the oral cavity, what suggests high effectiveness of the therapy protocol in the oral cavity, or it is possible that oral H. pylori is of a transient character.
MAGNETIC RESONANCE IMAGING FEATURES OF DISCOSPONDYLITIS IN DOGS
Authors: CARRERA INÉS , SULLIVAN MARTIN , MCCONNELL FRASER , GONÇALVES RITA
Published: December 2010

The diagnosis of discospondylitis is based mainly on diagnostic imaging and laboratory results. Herein, we describe the magnetic resonance imaging (MRI) findings in 13 dogs with confirmed discospondylitis. In total there were 17 sites of discospondylitis. Eleven (81.1%) of the dogs had spinal pain for >3 weeks and a variable degree of neurologic signs. Two dogs had spinal pain and ataxia for 4 days. Radiographs were available in nine of the dogs. In MR images there was always involvement of two adjacent vertebral endplates and the associated disk. The involved endplates and adjacent marrow were T1‐hypointense with hyperintensity in short tau inversion recovery (STIR) images in all dogs, and all dogs also had contrast enhancement of endplates and paravertebral tissues. The intervertebral disks were hyperintense in T2W and STIR images and characterized by contrast enhancement in 15 sites (88.2%). Endplate erosion was present in 15 sites (88.2%) and was associated with T2‐hypointense bone marrow adjacent to it. In two sites (11.8%) endplate erosion was not MR images or radiographically. The vertebral bone marrow in these sites was T2‐hyperintense. Epidural extension was conspicuous in postcontrast images at 15 sites (88.2%). Spinal cord compression was present at 15 sites (88.2%), and all affected dogs had neurologic signs. Subluxation was present in two sites (11.8%). MRI shows characteristic features of discospondylitis, and it allows the recognition of the exact location and extension (to the epidural space and paravertebral soft tissues) of the infection. Furthermore, MRI increases lesion conspicuity in early discospondylitis that may not be visualized by radiography.
IMAGING DIAGNOSIS—MAGNETIC RESONANCE IMAGING FINDINGS OF PRIMARY CEREBRAL HEMANGIOMA
Authors: EICHELBERGER BUNITA M. , KRAFT SUSAN L. , HALSEY CHARLES H. C. , PARK RICHARD D. , MILLER MATTHEW D. , KLOPP LISA
Published: December 2010

Intracranial hemangioma is a rare intraaxial hemorrhagic neoplasm with imaging characteristics similar to other intracranial hemorrhagic lesions. We describe two canine cerebral hemangiomas that appeared as poorly circumscribed intraaxial compressive lesions that were predominantly hypointense on T2 sequences and heterogeneously contrast enhancing. Both lesions had perilesional edema and were hypointense on T2*‐gradient recalled echo sequences, consistent with hemorrhage. In one tumor a short partial peripheral rim was present, which was suggestive of hemosiderin deposition. Cerebral hemangioma should be included as a differential for hemorrhagic intracranial lesions.
PULMONARY ANGIOGRAPHY USING 16 SLICE MULTIDETECTOR COMPUTED TOMOGRAPHY IN NORMAL DOGS
Authors: HABING AMY , COELHO JOANA C. , NELSON NATHAN , BROWN ANDREW , BEAL MATHEW , KINNS JENNIFER
Published: December 2010

We report a canine computed tomography (CT) pulmonary angiography technique using multidetector CT (MDCT). CT pulmonary angiography using a 16 slice MDCT was performed on five healthy, anesthetized beagles. A helical acquisition with pitch of 1.4 was used. The time delay for the angiographic study was determined using a bolus‐tracking program. A dose of 400 mg I/kg of nonionic contrast medium (Iohexol 300 mg I/ml) was administered to each dog via a cephalic catheter using an angiographic power injector at a rate of 5 ml/s. In two dogs a second study, using a contrast medium dose of 200 and 600 mg I/kg was performed. Arterial enhancement of transverse and reformatted images was classified subjectively as excellent, good, or poor, and assessed objectively by measuring Hounsfield units at the right main pulmonary artery. Angiographic studies were evaluated by two radiologists to determine the number of subsegmental arterial branches visualized. The median number of subsegmental arterial branches identified was five (range: 2–7). Based on the time attenuation curve obtained by the bolus‐tracking program, there was consistent enhancement of the right main pulmonary artery beginning at 6 s and peaking at 8 s in 4/5 dogs. The contrast medium dose of 400 mg I/kg produced good to excellent vascular enhancement in the same 4/5 dogs. A dose of 200 mg I/kg resulted in poor enhancement. CT pulmonary angiography using MDCT and an automated bolus‐tracking program allows rapid, consistent evaluation of the pulmonary vasculature using a single dose of 400 mg I/kg of contrast medium.
SAFETY AND CORRELATION OF TEST RESULTS OF COMBINED ULTRASOUND‐GUIDED FINE‐NEEDLE ASPIRATION AND NEEDLE CORE BIOPSY OF THE CANINE SPLEEN
Authors: WATSON ADAM T. , PENNINCK DOMINIQUE , KNOLL JOYCE S. , KEATING JOHN H. , SUTHERLAND‐SMITH JAMES
Published: December 2010

The safety and diagnostic value of combined splenic fine‐needle aspiration (FNA) and needle core biopsy (NCB) is unknown. Forty‐one dogs with splenic lesions were studied prospectively. Safety was assessed in 38 dogs and no complications were encountered. Initially, clinical and anatomic pathologists reviewed each FNA and NCB sample, respectively, without knowledge of the other's results. Diagnoses were categorized as neoplastic, benign, inflammatory, normal, or nondiagnostic. The level of agreement between sampling methods was categorized as complete, partial, disagreement, or not available. Test correlation was performed in 40 dogs. Nondiagnostic results occurred in 5/40 NCB (12.5%) and no FNA samples. Neoplasia was diagnosed in 17/40 dogs (42.5%), benign changes in 20/40 dogs (50%), inflammatory disorders in 0/40 dogs, and normal 2/40 dogs (5%). One of the 40 dogs (2.5%) had a diagnosis that was equivocal for neoplasia on both tests and therefore was not categorized. Of the 35 dogs that had diagnostic samples, cytopathologic and histopathologic diagnoses agreed completely in 18/35 dogs (51.4%), partially in 3/35 dogs (8.6%), and were in disagreement in 14/35 dogs (40.0%). Pathologists collaboratively reviewed diagnoses that were in disagreement or partial agreement and altered their individual diagnoses in 6/17 dogs (35.3%) to be within partial or complete agreement, respectively. Percutaneous FNA and NCB can be performed safely in dogs with sonographic splenic changes. Results suggest that adding NCB to FNA provides complementary information in dogs with suspected splenic neoplasia. This combined protocol may improve detection of splenic neoplasia and provide neoplastic subclassification.
STATIC AND DYNAMIC 18FDG‐PET IN NORMAL HISPANIOLAN AMAZON PARROTS (AMAZONA VENTRALIS)
Authors: SOUZA MARCY J. , WALL JONATHAN S. , STUCKEY ALAN , DANIEL GREGORY B.
Published: December 2010

Positron emission tomography (PET) is often used to stage and monitor human cancer and has recently been used in a similar fashion in veterinary medicine. The most commonly used radiopharmaceutical is 2‐Deoxy‐2‐[18F]‐Fluoro‐d‐glucose (18F‐FDG), which is concentrated and trapped within cells that use glucose as their energy substrate. We characterized the normal distribution of 18F‐FDG in 10 healthy Hispaniolan Amazon parrots (Amazona ventralis) by performing whole body PET scans at steady state, 60 min after injection. Significant variability was found in the intestinal activity. Avian species are known to reflux fluid and electrolytes from their cloaca into their colon. To evaluate reflux as the cause of variability in intestinal distribution of 18F‐FDG, dynamic PET scans were performed on the coelomic cavity of six Hispaniolan Amazon parrots from time 0 to 60 min postinjection of radiotracer. Reflux of radioactive material from the cloaca into the colon occurred in all birds to varying degrees and occurred before 60 min. To evaluate the intestinal tract of clinical avian patients, dynamic scans must be performed starting immediately after injection so that increased radioactivity due to metabolism or hypermetabolic lesions such as cancer can be differentiated from increased radioactivity due to reflux of fluid from the cloaca.
Structures of type B ribose 5‐phosphate isomerase from Trypanosoma cruzi shed light on the determinants of sugar specificity in the structural family
Authors: Stern Ana L. , Naworyta Agata , Cazzulo Juan J. , Mowbray Sherry L.
Published: December 2010

Ribose‐5‐phosphate isomerase (Rpi; EC 5.3.1.6) is a key activity of the pentose phosphate pathway. Two unrelated types of sequence/structure possess this activity: type A Rpi (present in most organisms) and type B Rpi (RpiB) (in some bacteria and parasitic protozoa). In the present study, we report enzyme kinetics and crystallographic studies of the RpiB from the human pathogen, Trypanosoma cruzi. Structures of the wild‐type and a Cys69Ala mutant enzyme, alone or bound to phosphate, d‐ribose 5‐phosphate, or the inhibitors 4‐phospho‐d‐erythronohydroxamic acid and d‐allose 6‐phosphate, highlight features of the active site, and show that small conformational changes are linked to binding. Kinetic studies confirm that, similar to the RpiB from Mycobacterium tuberculosis, the T. cruzi enzyme can isomerize d‐ribose 5‐phosphate effectively, but not the 6‐carbon sugar d‐allose 6‐phosphate; instead, this sugar acts as an inhibitor of both enzymes. The behaviour is distinct from that of the more closely related (to T. cruzi RpiB) Escherichia coli enzyme, which can isomerize both types of sugars. The hypothesis that differences in a phosphate‐binding loop near the active site were linked to the differences in specificity was tested by construction of a mutant T. cruzi enzyme with a sequence in this loop more similar to that of E. coli RpiB; this mutant enzyme gained the ability to act on the 6‐carbon sugar. The combined information allows us to distinguish the two types of specificity patterns in other available sequences. The results obtained in the present study provide insights into the action of RpiB enzymes generally, and also comprise a firm basis for future work in drug design.

Database
 Protein structures and diffraction data have been deposited in the Protein Data Bank (http://www.rcsb.org/pdb) under entry codes 3K7O, 3K7P, 3K7S, 3K8C and 3M1P for the wild‐type, mutant/Pi, R5P, 4PEH and mutant/All6P structures, respectively

Structured digital abstract

 MINT‐8081804, MINT‐8081814: TcRpiB (uniprotkb:A1BTJ7) and TcRpiB (uniprotkb:A1BTJ7)bind (MI:0407) by x‐ray crystallography (MI:0114)
A distinct sequence in the adenine nucleotide translocase from Artemia franciscana embryos is associated with insensitivity to bongkrekate and atypical effects of adenine nucleotides on Ca2+ uptake and sequestration
Authors: Konràd Csaba , Kiss Gergely , Töröcsik Beata , Lábár János L. , Gerencser Akos A. , Mándi Miklós , Adam‐Vizi Vera , Chinopoulos Christos
Published: December 2010

Mitochondria isolated from embryos of the crustacean Artemia franciscana lack the Ca2+‐induced permeability transition pore. Although the composition of the pore described in mammalian mitochondria is unknown, the impacts of several effectors of the adenine nucleotide translocase (ANT) on pore opening are firmly established. Notably, ADP, ATP and bongkrekate delay, whereas carboxyatractyloside hastens, Ca2+‐induced pore opening. Here, we report that adenine nucleotides decreased, whereas carboxyatractyloside increased, Ca2+ uptake capacity in mitochondria isolated from Artemia embryos. Bongkrekate had no effect on either Ca2+ uptake or ADP–ATP exchange rate. Transmission electron microscopy imaging of Ca2+‐loaded Artemia mitochondria showed needle‐like formations of electron‐dense material in the absence of adenine nucleotides, and dot‐like formations in the presence of adenine nucleotides or Mg2+. Energy‐filtered transmission electron microscopy showed the material to be rich in calcium and phosphorus. Sequencing of the Artemia mRNA coding for ANT revealed that it transcribes a protein with a stretch of amino acids in the 198–225 region with 48–56% similarity to those from other species, including the deletion of three amino acids in positions 211, 212 and 219. Mitochondria isolated from the liver of Xenopus laevis, in which the ANT shows similarity to that in Artemia except for the 198–225 amino acid region, demonstrated a Ca2+‐induced bongkrekate‐sensitive permeability transition pore, allowing the suggestion that this region of ANT may contain the binding site for bongkrekate.