bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytic Review: Thyrotoxic Periodic Paralysis: A Review
Authors: Pothiwala Pooja , Levine Steven N.
Published: January 2010

Thyrotoxic periodic paralysis (TPP) is an unusual complication of hyperthyroidism that frequently presents in a dramatic fashion, necessitating treatment in an emergency department or admission to an intensive care unit. Thyrotoxic periodic paralysis is characterized by transient, recurrent episodes of flaccid muscle paralysis affecting proximal more severely than distal muscles. Thyrotoxic periodic paralysis is most commonly a complication of Graves’ disease in Asian males, although in recent decades, an increasing number of patients from all racial and ethnic backgrounds have been reported. Thyrotoxic periodic paralysis has a higher predilection for men than women despite the fact that thyroid disease is more frequently diagnosed in women. The presence of both hypokalemia and elevated levels of triiodothyronine (T3) and thyroxine (T4) are important diagnostic features during the acute episode. Treatment of TPP involves 2 steps, immediate action to reverse the paralysis followed by measures to prevent future attacks by restoration of a euthyroid state. Although the mainstay of treating an acute attack of TPP is correction of hypokalemia to avoid fatal cardiac arrhythmias and reverse muscle weakness, it must be appreciated by treating physicians that patients with TPP do not have a total body deficiency of potassium. Close attention must be given to potassium replacement as overly aggressive treatment can result in hyperkalemia. Correction of hypokalemia and the underlying thyrotoxic state usually results in amelioration of the acute attack. This review summarizes the epidemiology, clinical manifestations, pathogenesis, diagnosis, and treatment of TPP.
Reassessing the Communist Takeover in Romania
Authors: Bottoni Stefano
Published: January 2010

This article analyzes the communist takeover in Romania as the successful outcome of a long-term policy aiming to make the Romanian Communist Party (PCR) a national force. Such an attempt deserves a new analytical explanation of the highly controversial notions of institutional continuity and of “nationalization” of its membership. While mainstream explanations still focus on factors of change motivated by external (Soviet) pressure and stress that violence, coercion, and intimidation have been main instruments used by the Communist Party to implement its goals, the author argues that a reevaluation of the real extent of popular support is needed. PCR became a national mass party immediately after the coup d’état of 23 August 1944. At that time a marginal political force, traditionally ruled by non-Romanian elements and devoted to the strictest internationalism, turned national without falling into discrimination against minority groups, with the exception of the Germans. In multiethnic Transylvania the ethnic power balance consciously created by PCR with Soviet assistance helped the party to strengthen its political legitimacy among different national and social groups. Unlike the Romanian historical parties and the Hungarian nationalists, the PCR and the Petru Groza—led coalition government behaved as a transnational body and pursued integrative policies. In the troubled context of postwar reconstruction, this call for cooperation and peaceful ethnic coexistence distinguished the PCR and its allies from the opposition parties and significantly contributed to make early communist rule more acceptable to large masses of Romanians and non-Romanians, as well.
Anti-Soviet Partisans and Ukrainian Memory
Authors: Marples David R.
Published: January 2010

The article examines how interpretations of the Organization of Ukrainian Nationalists and the Ukrainian Insurgent Army have changed in the period of Ukraine’s independence. By examining narratives from a wide-ranging selection of Ukrainian media, as well as school textbooks and other writings, the author asks whether scholars’ perspectives on the war years are as distorted as they were in the Soviet period. Has the former Soviet narrative been replaced by a nationalist one, at the expense of historical accuracy? Have the events in question become too politicized and too divisive to deal with?
Pancreatitis as initial manifestation of systemic lupus erythematosus
Authors: Essaadouni L. , Samar E. , Krati K.
Published: January 2010

Pancreatitis as an initial manifestation of systemic lupus erythematosus is rare. Two cases are reported of young female patients who presented with fever, abdominal pain, vomiting and elevated levels of pancreatic enzymes. They were diagnosed with acute severe pancreatitis associated with systemic lupus erythematosus. There are a few reports in the literature about this association, but the pathogenesis and treatment are still controversial.
Emotional anchoring and objectification in the media reporting on climate change
Authors: Höijer Birgitta
Published: January 2010

Using the framework of social representations theory — more precisely the concepts of anchoring and objectification — this article analyses the emotions on which the media reporting on climate change draws. Emotions are thereby regarded as discursive phenomena. A qualitative analysis of two series in Swedish media on climate change, one in a tabloid newspaper and one in public service television news, is presented showing how the verbal and visual representations are attached to emotions of fear, hope, guilt, compassion and nostalgia. It is further argued that emotional representations of climate change may on the one hand enhance public engagement in the issue, but on the other hand may draw attention away from climate change as the abstract, long-term phenomenon of a statistical character that it is.
Perceived efficacy and attitudes towards genetic science and science governance
Authors: Knight Terry , Barnett Julie
Published: January 2010

Arguments for public involvement in science and technology are often based on ideas of developing a more capable public and the assumed effects this may have for science. However, such a relationship is yet to be sufficiently explored and recent work indicates that a more involved public may have counterintuitive effects. Using nationally representative survey data for the UK and Northern Ireland, the effects of the public’s own beliefs about involvement are explored. Developing the concept of “belief in public efficacy,” findings suggest those who believe that the public might be able to affect the course of decision making have less approving attitudes towards future applications of genetic science; however, an individual’s political efficacy does not significantly influence these attitudes. Furthermore, political efficacy and belief in public efficacy have some distinct and opposing relationships with the principles of governance people prefer. Overall, findings provide support for suggestions that it is simplistic to consider increasing public involvement as a way of increasing the approval of risky new technologies.
Predictors of Adopting Motivational Enhancement Therapy
Authors: Ager Richard , Roahen-Harrison Stephanie , Toriello Paul J. , Kissinger Patricia , Morse Patricia , Morse Edward , Carney Linton , Rice Janet
Published: January 2010

Substance abuse counselors have shown limited success in adopting evidence-based practices (EBPs). The purpose of this paper is to identify the barriers and facilitators of adopting an EBP called motivational enhancement therapy (MET). One hundred thirty-six predominantly female (60%) African American (68%) addiction counselors representing over 40 agencies completed surveys before and after participating in a 2-day MET training. Based on stepwise regressions, 10 variables predicted gains in MET knowledge, attitudes, and/or skills: high consistency of MET with organization’s philosophy, being Caucasian, being younger, low self-efficacy, high practitioner self-perceived cultural competency, low adherence to the 12-step treatment philosophy, viewing MET as challenging to learn, high workload, fewer colleagues in same MET training, and working in a smaller organization. Implications for social work practice are discussed.
General Practice Utilization After Sexual Victimization: A Case Control Study
Authors: Elklit Ask , Shevlin Mark
Published: January 2010

There is a growing research literature that indicates that sexual victimization results in increased physical health problems and health service utilization. This study aimed to examine the relationship between attendance at a center for rape victims and frequency of contact with general practitioners. The study used matched case-control design, and information about general practitioner use over a 7-year period was drawn from the Danish Civil Registration System. There was a sustained increase in health care use for those who had used the center for rape victims compared to the control group.
Coming Back Normal: The Process of Self-Recovery in Those With Schizophrenia
Authors: Shea Joyce M.
Published: January 2010

BACKGROUND: Researchers have identified the reestablishment of self-identity as a key part of recovery in individuals with schizophrenia. Previous studies have increased scholars’ understanding about how and when identity changes occur in those with schizophrenia; less is understood about the process by which individuals with schizophrenia reconstruct their self-identity. OBJECTIVE: The objective of this study is to describe the process of self-identity reconstruction in people with schizophrenia. STUDY DESIGN: A grounded theory study was conducted with 10 purposively selected participants and 4 significant others; 19 semistructured interviews were completed. RESULTS: Constant comparative analysis led to a theory of a six-stage process of self-recovery in those with schizophrenia. For some participants, the successful struggle to care for a new self led to the refinement and eventual recovery of self-identity. CONCLUSIONS: Individuals with schizophrenia experience a process of distinct changes in self-identity occurring between engulfment by a severe mental illness and emergence of a new self.
Does International Diversification Discount Exist in the Hotel Industry?
Authors: Tang Chun-Hung , Jang SooCheong
Published: January 2010

The primary objective of this study was to investigate the value of international diversification in hotel firms. The results show that although diversification discounts exist, the relationship between international diversification and excess value is curvilinear (U-shaped), suggesting that highly diversified hotel firms could still benefit from international diversification. The comparison between absolute market premium (excess market value) and relative market premium (excess Q) also indicates that international diversification can increase the value of intangible assets, but a firm’s ability to leverage its intangible assets through international diversification differs because of industry characteristics. Implications for the hotel industry are also discussed.
Factors Affecting Franchise Decisions in the Restaurant Industry
Authors: Hsu Li-Tzang , SooCheong Jang  , Canter Deborah D.
Published: January 2010

Franchising captures a sizeable portion of the restaurant industry and plays an important role in its growth. However, despite the importance of franchising to the restaurant industry, little has been done to investigate the characteristics of restaurant firms that engage in franchising. This study intends to explain what characteristics of restaurant firms relate to franchising. Accordingly, a logistic regression model was developed to identify variables that best differentiate restaurant franchisor firms from nonfranchisor firms. The results indicated that (a) the degree of geographic dispersion and involvement in foreign countries increases the probability of becoming a restaurant franchisor; (b) as a restaurant firm ages, the probability of franchising decreases; and (c) the decrease of specific knowledge requirements increases the probability of franchising. This study also provides suggestions to help restaurant firms considering franchising for their operations.
The role of hyperbaric oxygen therapy in trauma
Authors: Williams Simon TB
Published: January 2010

This review explains the method of action of hyperbaric oxygenation (HBO) therapy and examines the evidence for its use in trauma. Methods of delivery, complications and contra-indications are discussed. It is acknowledged that there are few controlled trials which evaluate the efficacy of HBO in this indication; supporting evidence for its efficacy is mainly in the form of case reports, or by implication from laboratory and animal work. Lack of evidence may not equate to lack of efficacy, but may reflect the difficulties in coordinating clinical trials involving critically ill patients and a complex treatment modality, the availability of which is not widespread. The adjunctive use of HBO has shown promising results in the treatment of crush injury. Consideration of tissue pathophysiology suggests that such an approach may also offer improved outcomes in the broader spectrum of trauma scenarios involving marginally viable tissues with compromised perfusion.
Dorsally angulated fractures of the distal radius
Authors: Deakin DE , Deshmukh SC
Published: January 2010

Management of unstable distal radius fractures has evolved considerably in recent years. This review describes the assessment and management of distal radius fractures in light of these recent changes.
Endothelin-1 receptor blockade induces upregulation of renin-angiotensin-aldosterone system expression in terms of blood pressure regulation
Authors: Bo Yang  , Chen Yun-Dai , Li Tian-De , Feng Quan-Zhou
Published: January 2010

Objective. To compare the level of expression of the renin-angiotensin-aldosterone system (RAAS) in mice with or without the endothelin-1 receptor antagonist bosentan and to examine the potential value in blood pressure regulation.

Materials and methods. Bosentan (10 mg/kg/d) and placebo were given to two groups of male C57BL/6 mice (n=5) from ages 6 to 12 weeks. The mRNAs of liver, kidney and lung were isolated for Northern blot analysis. A further 15 male C57BL/6 mice were divided into three groups (n=5): mice in group A were given the angiotensin II type 1 receptor blocker valsartan (10 mg/kg/d); mice in group B were given bosentan (10 mg/kg/d); and mice in group C were given both valsartan and bosentan (10 mg/ kg/d for each drug). All mice were administered the drugs from 6 to 12 weeks of age and had their systolic blood pressure (SBP) measured at the end of the drug treatments.

Results. Northern blot analysis demonstrated that the expression levels of angiotensinogen in liver (p=0.0126), renin in kidney (p=0.002), and angiotensin-converting enzyme in lung (p=0.0041) were upregulated in mice treated with bosentan. No difference in SBP was found among the groups before drug administration. Six weeks after monotherapy with valsartan, SBP was slightly lowered (126±2 vs. 122±3 mmHg, p=0.0381). Monotherapy with bosentan also had a small effect on SBP (126±2 vs. 122±3 mmHg, p=0.0381), whereas dual blockade with valsartan and bosentan significantly lowered SBP (127±3 vs. 103±3 mmHg, p<0.001). Conclusions. We conclude that RAAS components are upregulated under endothelin blockade. Dual blockade of the RAAS and endothelin system is beneficial for blood pressure control.
Theorizing Practice and Practising Theory: Outlines for an Actor-Relational-Approach in Planning
Authors: Boelens Luuk
Published: January 2010

Not only in the Netherlands, but also elsewhere, there is stalemate between modern and postmodern/post-structural planning, or alternatively, between state-controlled and neo-liberal planning. Since the 1980s at least, modernist, state-controlled planning has been fundamentally debunked as a highly regulatory and prescriptive operation, resulting in syrupy planning processes, which are very costly, inflexible and inefficient, and suppressing all new and creative initiatives that do not fit within the set framework. Postmodern and post-structural alternatives developed since then have been very effective in counter-attacking the alleged virtues of that planning strategy, but less fruitful at promoting effective and/or sustainable practices. The article assumes that this is related to the fact that time and again these alternatives continue to be formulated from within the existing planning framework, from a specific governmental, or at least a government influenced, view of planning: in essence from the inside-out. From this position, the article goes on to describe the possible outlines for a practical outside-inward, actor-relational-approach. It has been developed from experimental case studies in concrete planning practices, for example, a case study in Southern Limburg in the Netherlands. Concurrently, it has also been derived from a fundamental interaction with behavioural, urban regime and actor-network/network actor theories, with an extensive evaluation of the latter. The article concludes with a call for a new fundamental, but proactive, reassembling of spatial planning in an actor-oriented, as opposed to a government-oriented, way.
Writing History
Authors: Wrigglesworth John , McKeever Mary
Published: January 2010

In order to write successfully, students need to understand what it is they are expected to write, why it is written in a particular way and the form that the final text should take. Linguistics research indicates that the ubiquitous essay and report conceal significant disciplinary variation. Educational research reveals variation with regard to assessment and marking of written work within disciplines, between lecturers, across departments, nationally and internationally. We present an interdisciplinary, genre-based model that we have piloted and tested in History at the University of Portsmouth. Our aim is to bring disciplinary, applied linguistic and academic skills expertise to the point where students are taught to write particular assignments. We offer the model for testing in other genres, disciplines and institutions.
Civic Engagement and Global Citizenship in a University Context
Authors: Munck Ronaldo
Published: January 2010

Can civic engagement become a ‘core business’ of the contemporary university, or is it an attractive ‘add-on’ that is not affordable in the current economic climate? Contemporary universities often play an important role in local community development and, as such, have the opportunity to develop civic engagement strategies to sit alongside teaching and research strategies. Yet the contemporary university is also internationally engaged, and the strategy of educating graduates to become global citizens could also become part of the key functions of ‘socially embedded’ universities. Ronaldo Munck explains how Dublin City University is attempting to negotiate the requirements of the economy with the demands of citizenship.
Carelessness: A hidden doxa of higher education
Authors: Lynch Kathleen
Published: January 2010

This article explores the implications of new public sector ‘reforms’ for the culture of higher education. It argues that a culture of carelessness, grounded in Cartesian rationalism, has been exacerbated by new managerialism. The article challenges a prevailing sociological assumption that the character of higher education culture is primarily determined by new managerial values and norms. Carelessness in education has a longer historical trajectory. First, it has its origins in the classical Cartesian view of education, namely that scholarly work is separate from emotional thought and feeling, and that the focus of education is on educating an autonomous, rational person, homo sapiens, whose relationality is not regarded as central to her or his being. Second, it is grounded in the separation between fact and value that is endemic to contemporary positivist norms that govern not only scientific and social scientific thought (Sayer, 2006) but the organization of higher education (Grummell et al., 2009a; Lynch, 2006). What is new about new managerialism in higher education is the moral status it accords to carelessness. Given the moral imperative on women to do care work (O’Brien, 2007) and on men to be care-less, the carelessness of higher education has highly gendered outcomes.1
Advanced Theory of Mind in Children Using Augmentative and Alternative Communication
Authors: Sundqvist Anett , Rönnberg Jerker
Published: January 2010

This study focused on the attainment of Theory of Mind (ToM) in children (aged 6 to 13) with complex communication needs who used augmentative and alternative communication (AAC). The AAC group ( n = 14) was matched to a younger group, without disabilities, vis-à-vis nonverbal mental age. A second comparison group consisting of children with mild intellectual disabilities and matched nonverbal mental age and chronological age was also included. A test battery that included tests of cognitive and language development and tests of first- and second-order ToM understanding and understanding of more advanced ToM was used. Nonverbal intelligence proved to be a good indicator of ToM ability. Contrary to previous research, the AAC group did not differ significantly from the comparison groups on the test results. The results are discussed in terms of the necessary cognitive capacity underpinning ToM development.
Resilience among very old men and women
Authors: Aléx Lena
Published: January 2010

High resilience is characterised by qualities of equanimity, perseverance, self-reliance, meaningfulness and existential aloneness. The aims of the present study were both to explore how the oldest of old men and women with estimated high resilience talk about experiences of becoming and being old, and to discuss the analysis of their narratives in terms of the foundational concepts of the Resilience Scale (RS). Thematic narrative interviews collected from 24 old people were analysed using content analysis, and the following themes were identified: feeling connected, feeling independent and creating meaning. The themes can be seen as congruent with the underlying concepts of the Resilience Scale; however, the themes were markedly gendered. A combination of both quantitative and qualitative research may contribute to a new angle of approach towards our understanding of resilience. In nursing practice it is of importance to both stimulate social contacts in the present and listen to narratives from the past to increase resilience among the oldest patients.
The Unbearable Limitations of Journalism
Authors: Broersma Marcel
Published: January 2010

Though the impossibility of a mimetic and purely objective representation of reality is commonly accepted, it is striking that journalism's claim to truth and authenticity is still so vivid in journalism and in public discourse. Its supposed ability to to mirror reality by verifying true facts remains the basic assumption underlying press critique, as becomes clear in for example the books of Nick Davies and Joris Luyendijk who both criticize journalism for its inability to represent social reality accurately. This article contends that to go beyond the unbearable limitations of journalism and understand how it works, we should not approach journalism as a descriptive discourse but on the contrary as a performative discourse designed to persuade readers that what it describes is real. By successfully doing so, journalism transforms an interpretation into truth — into a reality the public can act upon. It is furthermore argued that journalism does not derive its performative power from its contents (the facts), but merely from its forms and style. News consumers tend to believe the contents that come with professional routines and conventions, justifying and masking the subjective interpretation and news selection of the individual journalist. If we acknowledge that journalism is a performative discourse it is impossible to be transparent about its limitations and its inability to discover the truth and introduce structural ambiguity in news writing as is suggested by press critics.
News, Transparency and the Effectiveness of Reporting From Inside Arab Dictatorships
Authors: Sakr Naomi
Published: January 2010

Contradictions in Egyptian media laws, whereby draconian emergency censorship powers coexist with apparently lively media output, seriously affect the content of foreign press reporting from Cairo. Taking account of theories about the way news production norms in free societies marginalize insights into the political structures of societies that are not free, this article examines treatment of struggles that took place in Egypt in 2008 over the licensing of news media and journalists. It finds that, because these struggles involved legal processes not marked by obvious crisis, the full extent of repression they reflected was rarely conveyed in foreign news reports.
The Neglect of Africa and the Power of Aid
Authors: Franks Suzanne
Published: January 2010

/ Since the end of colonial rule, Africa has on the whole been inadequately covered by the western media. It is rarely reported except as a backdrop to disaster or as the scene of a celebrity visit. There is an absence of sustained and well-informed reporting about Africa in the mainstream media. And when the media do cover it they often get the story very wrong, partly because there is no ongoing understanding of and engagement with the continent. Using exclusive access to the BBC archive, the article examines how and why media coverage of Africa has been misleading and misinformed in the postcolonial period. It examines the extent to which the close relationship between media coverage and aid agencies has damaged the cause of informing the public. Aid agencies have seen a huge growth since the mid-1980s — partly precipitated by the power of media imagery. As media organizations have reduced their commitment to investing in reporting on Africa so journalists have in turn become more dependent upon aid agencies, which have filled a vacuum. This symbiotic relationship requires a degree of transparency otherwise there is a danger that it can compromise journalistic accountability.
The Framing of Islam On Network News Following the September 11Th Attacks
Authors: Ibrahim Dina
Published: January 2010

/ This article investigates the shifting discourse on Islam and Muslims in the immediate aftermath of the 9/11 attacks. It seeks to investigate and compare the visual and verbal frames used to describe Islam within and outside America, which aspects of the religion were emphasized or omitted and how closely the frames of Islam concurred with the ideology of officials. Through this case study of American network news coverage post-9/11, the article argues that objective coverage of Islam is a myth, not just in America, but across the world. The author supports the problematic but necessary remedial action of urging reporters to acknowledge their subjectivity and find ways to increase their transparency regarding the choices they make in constructing their frames.
Nutritional Intake and Therapies in Autism
Authors: Geraghty Maureen E. , Depasquale Gina M. , Lane Alison E.
Published: January 2010

Autism is one of the fastest growing developmental disabilities in the United States. With every 1 in 100 children diagnosed with autism, this condition is more common than pediatric cancer, diabetes, and AIDS combined. Core deficits of autism limit functioning in social interaction, communication, and daily activity participation. Individuals with autism typically require significant levels of supervised care, special education resources, and health service throughout life. The nutritional status of children with autism is receiving increasing attention in the field. Nutrient deficiencies have been proposed as a causative factor in the manifestation of the disorder. Further, characteristic autism behaviors and autism-specific interventions may increase the risk of suboptimal nutrition. Part 1 of this paper provides a review as to what is currently known regarding the nutrient intake and/or nutritional status of children with autism, and the myriad factors—both medical/nutritional and behavioral/ contextual—likely to impact dietary intake and nutritional status. Part 2 explores nutrition interventions (special diets and dietary supplements or “biomedical” interventions) in terms of safety and efficacy, as well as behavioral interventions used in autism spectrum disorder.
Breast Milk Versus Formula
Authors: Lee Mendoza Roger
Published: January 2010

This study addresses the following research questions: How efficient is the judicial process in resolving health and nutrition policy conflicts that inevitably entail a cost-benefit calculus? What are its corresponding policy implications? The case method was used based on an illustrative, landmark decision of the Supreme Court of the Philippines concerning milk formula marketing. Comparative country experiences in implementing the International Code of Marketing of Breast-Milk Substitutes were surveyed for this study. The study underscores the vital initiatives taken by the Philippines as a model for other countries in promoting, protecting, and supporting breastfeeding. However, it finds that the institutional capacities of courts to gather, process, and evaluate health-related information are limited, even when courts adopt a posture of restraint. The adversarial structure of litigation, the assumptions and expectations of litigants and judges, and the normative orientation and methodology of adjudication breed reliance on information asymmetries, as depicted in mathematical equations developed in this study. The study contributes to current scholarship on the judicial process and health marketing by drawing attention to key information asymmetries in litigation and adjudication. It suggests that courts be viewed as a last resort in health and nutrition policy conflicts and advocacy. Political and administrative processes should be revisited for possible accommodation following judicial settlement of policy disputes.
microRNA-34a expression correlates with MDM2 SNP309 polymorphism and treatment-free survival in chronic lymphocytic leukemia
Authors: Asslaber Daniela , Piñón Josefina D. , Seyfried Irina , Desch Petra , Stöcher Markus , Tinhofer Inge , Egle Alexander , Merkel Olaf , Greil Richard
Published: January 2010

In chronic lymphocytic leukemia (B-CLL), aberrations along the p53 axis lead to decreased overall survival and therapy resistance. Recent studies identified microRNA-34a (miR-34a) as a major downstream target of p53. We monitored the expression of miR-34a during disease development in a murine B-CLL model. miR-34a was up-regulated more than 20-fold during the leukemic but not during the preleukemic phase. In the human system, B-CLL cells also had 4.6-fold higher miR-34a expression compared with B cells of healthy controls. In B-CLL cells of patients with p53 aberrations, miR-34a expression was consistently low. The broad distribution of miR-34a levels in p53 wild-type patients prompted us to study the correlation between single nucleotide polymorphism 309 (SNP309) in the intronic promoter of MDM2 and miR-34a expression. B-CLL cells of patients with the SNP309 GG genotype had significantly lower miR-34a expression levels compared with patients with the TT genotype (P = .002). Low miR-34a levels were able to predict shorter time to treatment (P = .003) and were associated with an abbreviated lymphocyte doubling time. Further, overexpression of miR-34a in primary B-CLL cells induced apoptosis. These findings suggest miR-34a as a possible therapeutic avenue and a sensitive indicator of the activity of the p53 axis in B-CLL.
B cell–specific lentiviral gene therapy leads to sustained B-cell functional recovery in a murine model of X-linked agammaglobulinemia
Authors: Kerns Hannah M. , Ryu Byoung Y. , Stirling Brigid V. , Sather Blythe D. , Astrakhan Alexander , Humblet-Baron Stephanie , Liggitt Denny , Rawlings David J.
Published: January 2010

The immunodeficiency disorder, X-linked agammaglobulinemia (XLA), results from mutations in the gene encoding Bruton tyrosine kinase (Btk). Btk is required for pre-B cell clonal expansion and B-cell antigen receptor signaling. XLA patients lack mature B cells and immunoglobulin and experience recurrent bacterial infections only partially mitigated by life-long antibody replacement therapy. In pursuit of definitive therapy for XLA, we tested ex vivo gene therapy using a lentiviral vector (LV) containing the immunoglobulin enhancer (Eμ) and Igβ (B29) minimal promoter to drive B lineage–specific human Btk expression in Btk/Tec−/− mice, a strain that reproduces the features of human XLA. After transplantation of EμB29-Btk-LV–transduced stem cells, treated mice showed significant, albeit incomplete, rescue of mature B cells in the bone marrow, peripheral blood, spleen, and peritoneal cavity, and improved responses to T-independent and T-dependent antigens. LV-treated B cells exhibited enhanced B-cell antigen receptor signaling and an in vivo selective advantage in the peripheral versus central B-cell compartment. Secondary transplantation showed sustained Btk expression, viral integration, and partial functional responses, consistent with long-term stem cell marking; and serial transplantation revealed no evidence for cellular or systemic toxicity. These findings strongly support pursuit of B lineage–targeted LV gene therapy in human XLA.
Knockdown of Fanconi anemia genes in human embryonic stem cells reveals early developmental defects in the hematopoietic lineage
Authors: Tulpule Asmin , Lensch M. William , Miller Justine D. , Austin Karyn , D'Andrea Alan , Schlaeger Thorsten M. , Shimamura Akiko , Daley George Q.
Published: January 2010

Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies. The effect of FA gene deficiency on hematopoietic development in utero remains poorly described as mouse models of FA do not develop hematopoietic failure and such studies cannot be performed on patients. We have created a human-specific in vitro system to study early hematopoietic development in FA using a lentiviral RNA interference (RNAi) strategy in human embryonic stem cells (hESCs). We show that knockdown of FANCA and FANCD2 in hESCs leads to a reduction in hematopoietic fates and progenitor numbers that can be rescued by FA gene complementation. Our data indicate that hematopoiesis is impaired in FA from the earliest stages of development, suggesting that deficiencies in embryonic hematopoiesis may underlie the progression to bone marrow failure in FA. This work illustrates how hESCs can provide unique insights into human development and further our understanding of genetic disease.
A comparative study of prenatal development in Miniopterus schreibersii fuliginosus, Hipposideros armiger and H. pratti
Authors: Wang Zhe , Han Naijian , Racey Paul A , Ru Binghua , He Guimei
Published: January 2010

Background

Bats comprise the second largest order of mammals. However, there are far fewer morphological studies of post-implantation embryonic development than early embryonic development in bats.

Results

We studied three species of bats (Miniopterus schreibersii fuliginosus, Hipposideros armiger and H. pratti), representing the two suborders Yangochiroptera and Yinpterochiroptera. Using an established embryonic staging system, we identified the embryonic stages for M. schreibersii fuliginosus, H. armiger and H. pratti and described the morphological changes in each species, including the development of the complex and distinctive nose-leaves in H. armiger and H. pratti. Finally, we compared embryonic and fetal morphology of the three species in the present study with five other species for which information is available.

Conclusion

As a whole, the organogenetic sequence of bat embryos is uniform and the embryos appear homoplastic before Stage 16. Morphological differentiation between species occurs mainly after embryonic Stage 16. Our study provides three new bat species for interspecific comparison of post-implantation embryonic development within the order Chiroptera and detailed data on the development of nose-leaves for bats in the superfamily Rhinolophoidea.
Gene expression profiling to identify eggshell proteins involved in physical defense of the chicken egg
Authors: Jonchère Vincent , Réhault-Godbert Sophie , Hennequet-Antier Christelle , Cabau Cédric , Sibut Vonick , Cogburn Larry A , Nys Yves , Gautron Joel
Published: January 2010

Background

As uricoletic animals, chickens produce cleidoic eggs, which are self-contained bacteria-resistant biological packages for extra-uterine development of the chick embryo. The eggshell constitutes a natural physical barrier against bacterial penetration if it forms correctly and remains intact. The eggshell's remarkable mechanical properties are due to interactions among mineral components and the organic matrix proteins. The purpose of our study was to identify novel eggshell proteins by examining the transcriptome of the uterus during calcification of the eggshell. An extensive bioinformatic analysis on genes over-expressed in the uterus allowed us to identify novel eggshell proteins that contribute to the egg's natural defenses.

Results

Our 14 K Del-Mar Chicken Integrated Systems microarray was used for transcriptional profiling in the hen's uterus during eggshell deposition. A total of 605 transcripts were over-expressed in the uterus compared with the magnum or white isthmus across a wide range of abundance (1.1- to 79.4-fold difference). The 605 highly-expressed uterine transcripts correspond to 469 unique genes, which encode 437 different proteins. Gene Ontology (GO) analysis was used for interpretation of protein function. The most over-represented GO terms are related to genes encoding ion transport proteins, which provide eggshell mineral precursors. Signal peptide sequence was found for 54 putative proteins secreted by the uterus during eggshell formation. Many functional proteins are involved in calcium binding or biomineralization--prerequisites for interacting with the mineral phase during eggshell fabrication. While another large group of proteins could be involved in proper folding of the eggshell matrix. Many secreted uterine proteins possess antibacterial properties, which would protect the egg against microbial invasion. A final group includes proteases and protease inhibitors that regulate protein activity in the acellular uterine fluid where eggshell formation takes place.

Conclusions

Our original study provides the first detailed description of the chicken uterus transcriptome during formation of the eggshell. We have discovered a cache of about 600 functional genes and identified a large number of encoded proteins secreted into uterine fluid for fabrication of the eggshell and chemical protection of the egg. Some of these uterine genes could prove useful as biological markers for genetic improvement of phenotypic traits (i.e., egg and eggshell quality).
Heterologous expression of glucose oxidase in the yeast Kluyveromyces marxianus
Authors: Rocha Saul N , Abrahão-Neto José , Cerdán María E , González-Siso María I , Gombert Andreas K
Published: January 2010

Background

In spite of its advantageous physiological properties for bioprocess applications, the use of the yeast Kluyveromyces marxianus as a host for heterologous protein production has been very limited, in constrast to its close relative Kluyveromyces
lactis. In the present work, the model protein glucose oxidase (GOX) from Aspergillus niger was cloned into K. marxianus CBS 6556 and into K. lactis CBS 2359 using three different expression systems. We aimed at verifying how each expression system would affect protein expression, secretion/localization, post-translational modification, and biochemical properties.

Results

The highest GOX expression levels (1552 units of secreted protein per gram dry cell weight) were achieved using an episomal system, in which the INU1 promoter and terminator were used to drive heterologous gene expression, together with the INU1 prepro sequence, which was employed to drive secretion of the enzyme. In all cases, GOX was mainly secreted, remaining either in the periplasmic space or in the culture supernatant. Whereas the use of genetic elements from Saccharomyces cerevisiae to drive heterologous protein expression led to higher expression levels in K. lactis than in K. marxianus, the use of INU1 genetic elements clearly led to the opposite result. The biochemical characterization of GOX confirmed the correct expression of the protein and showed that K. marxianus has a tendency to hyperglycosylate the protein, in a similar way as already observed for other yeasts, although this tendency seems to be smaller than the one of e.g. K. lactis and S. cerevisiae. Hyperglycosylation of GOX does not seem to affect its affinity for the substrate, nor its activity.

Conclusions

Taken together, our results indicate that K. marxianus is indeed a good host for the expression of heterologous proteins, not only for its physiological properties, but also because it correctly secretes and folds these proteins.
Isolation, characterization and heterologous expression of a novel chitosanase from Janthinobacterium sp. strain 4239
Authors: Johnsen Mads G , Hansen Ole C , Stougaard Peter
Published: January 2010

Background

Chitosanases (EC 3.2.1.132) hydrolyze the polysaccharide chitosan, which is composed of partially acetylated β-(1,4)-linked glucosamine residues. In nature, chitosanases are produced by a number of Gram-positive and Gram-negative bacteria, as well as by fungi, probably with the primary role of degrading chitosan from fungal and yeast cell walls for carbon metabolism. Chitosanases may also be utilized in eukaryotic cell manipulation for intracellular delivery of molecules formulated with chitosan as well as for transformation of filamentous fungi by temporal modification of the cell wall structures.

However, the chitosanases used so far in transformation and transfection experiments show optimal activity at high temperature, which is incompatible with most transfection and transformation protocols. Thus, there is a need for chitosanases, which display activity at lower temperatures.

Results

This paper describes the isolation of a chitosanase-producing, cold-active bacterium affiliated to the genus Janthinobacterium. The 876 bp chitosanase gene from the Janthinobacterium strain was isolated and characterized. The chitosanase was related to the Glycosyl Hydrolase family 46 chitosanases with Streptomyces chitosanase as the closest related (64% amino acid sequence identity). The chitosanase was expressed recombinantly as a periplasmic enzyme in Escherichia coli in amounts about 500 fold greater than in the native Janthinobacterium strain. Determination of temperature and pH optimum showed that the native and the recombinant chitosanase have maximal activity at pH 5-7 and at 45°C, but with 30-70% of the maximum activity at 10°C and 30°C, respectively.

Conclusions

A novel chitosanase enzyme and its corresponding gene was isolated from Janthinobacterium and produced recombinantly in E. coli as a periplasmic enzyme. The Janthinobacterium chitosanase displayed reasonable activity at 10°C to 30°C, temperatures that are preferred in transfection and transformation experiments.
Role of senescence and mitotic catastrophe in cancer therapy
Authors: Singh Richa , George Jasmine , Shukla Yogeshwer
Published: January 2010

Senescence and mitotic catastrophe (MC) are two distinct crucial non-apoptotic mechanisms, often triggered in cancer cells and tissues in response to anti-cancer drugs. Chemotherapeuticals and myriad other factors induce cell eradication via these routes. While senescence drives the cells to a state of quiescence, MC drives the cells towards death during the course of mitosis. The senescent phenotype distinguishes tumor cells that survived drug exposure but lost the ability to form colonies from those that recover and proliferate after treatment. Although senescent cells do not proliferate, they are metabolically active and may secrete proteins with potential tumor-promoting activities. The other anti-proliferative response of tumor cells is MC that is a form of cell death that results from abnormal mitosis and leads to the formation of interphase cells with multiple micronuclei. Different classes of cytotoxic agents induce MC, but the pathways of abnormal mitosis differ depending on the nature of the inducer and the status of cell-cycle checkpoints. In this review, we compare the two pathways and mention that they are activated to curb the growth of tumors. Altogether, we have highlighted the possibilities of the use of senescence targeting drugs, mitotic kinases and anti-mitotic agents in fabricating novel strategies in cancer control.
Comparison of the epidermal growth factor receptor protein expression between primary non-small cell lung cancer and paired lymph node metastases: implications for targeted nuclide radiotherapy
Authors: Rao Chuangzhou , Hu Qiongge , Ma Jianhua , Li Jian , Zhang Chen , Shen Li , Wei Qichun
Published: January 2010

Background

The knowledge of Epidermal growth factor receptor (EGFR) expression in metastases of NSCLC was limited. In receptor-mediated targeted nuclide radiotherapy, tumor cells are killed with delivered radiation and therapeutic efficiency is mainly dependent on the receptor expression. Thus, the level and stability of receptor expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as target. The goal of this study was to evaluate whether EGFR is suitable as target for clinical therapy.

Methods

Expression of EGFR was investigated immunohistochemically in paired samples of lymph node metastases and corresponding NSCLC primary lesions (n = 51). EGFR expression was scored as 0, 1+, 2+ or 3+.

Results

Positive (1+, 2+ or 3+) EGFR immunostaining was evident in 36 of 47 (76.6%) analysed NSCLC primary tumors, and in 78.7% of the corresponding lymph node metastases. When EGFR expression is classified as positive or negative, discordance between the primary tumors and the corresponding metastases was observed in 5 cases (10.6%). EGFR overexpression (2+ or 3+) was found in 53.2% (25/47) of the NSCLC primary tumors and 59.6% of the corresponding metastases. Nine out of the 47 paired samples (19.2%) were discordant: Only three patients who had EGFR overexpression in the primary tumors showed EGFR downregulation (0 or 1+) in lymph node metastases, while six patients changed the other way around.

Conclusions

The EGFR expression in the primary tumor and the corresponding metastasis is discordant in about 10% of the patients. When overexpression is considered, the discordance is observed in about 20% of the cases. However, concerning EGFR overexpression in the primary tumors, similar expression in the metastases could be predicted with a reasonably high probability, which is encouraging for testing of EGFR targeted nuclide radiotherapy.
An incidentally detected hepatic subcapsular hematoma in a very low birth weight newborn: a case report
Authors: Ahn Hye Shin , Chang Yun-Woo , Lee Dong Whan , Kwon Kui Hyang , Yang Seung Boo
Published: January 2010

Introduction

A hepatic subcapsular hematoma in a neonate shows a non-specific presentation such as the presence of an abdominal mass without symptoms of hemorrhage and is clinically less distinguished as compared to cases detected during an autopsy.

Case presentation

A neonate was delivered by vaginal delivery after 29 weeks and three days gestation with breech presentation. In a laboratory study, there were slightly increased levels of liver enzymes but the platelet count and hemoglobin level were normal. An abdomen ultrasonography and CT image demonstrated the cystic mass containing an internal thin septum with compression of the lateral margin of the right hepatic lobe and Morison's pouch. A CT image showed an irregular low-density lesion in the dome of liver that was suspected parenchymal laceration.

Conclusion

We have described the sonographic and CT findings of an incidentally detected subcapsular hematoma of the liver in a neonate who showed a breech presentation, very low birth weight and was premature.