bluuebunny/crossref_metadata_2025 huggingface dataset:
International Human Rights Law and Social Movements: States' Resistance and Civil Society's Insistence
Authors: Tsutsui Kiyoteru , Whitlinger Claire , Lim Alwyn
Published: August 2012

This review examines recent scholarship on the rise of international human rights law and proposes that social movements have played critical roles both in elevating the standards of human rights in international law and in leveraging these standards into better local practices. Institutionalization of universal human rights principles began in the immediate post–World War II period, in which civil society actors worked with powerful states to establish human rights as a key guiding principle of the international community and to ensure the actors' continuing participation in international human rights institutions. The subsequent decades saw various hurdles arise in international politics, but civil society actors skillfully used the small openings that they had gained to continue to advance the cause of human rights. They held powerful governments accountable to their lofty promises about human rights and worked with sympathetic governments in the UN system to continuously upgrade the standards of international human rights. They also leveraged human rights laws toward better local practices, taking advantage of new political opportunities created by human rights laws, using expanding international channels to increase flows of human and material resources, embracing globally legitimated vocabularies of human rights to frame their movements, and integrating the broad cultural effects of human rights laws to construct new social movement identity and actorhood. The review then points out some potential pitfalls of international human rights laws: professionalization of movement actors, which can undermine the impact of social movements and lead to less ambitious and transformative goals; privileging of some causes over others, which can lead to demobilization around certain issues; and overextending movement goals, which can give rise to strong backlash against human rights principles.
Staphylococcal Infections: Mechanisms of Biofilm Maturation and Detachment as Critical Determinants of Pathogenicity
Authors: Otto Michael
Published: August 2012

Biofilm-associated infections are a significant cause of morbidity and death. Staphylococci, above all Staphylococcus aureus and S. epidermidis, are the most frequent causes of biofilm-associated infections on indwelling medical devices. Although the mechanistic basis for the agglomeration of staphylococcal cells in biofilms has been investigated in great detail, we lack understanding of the forces and molecular determinants behind the structuring of biofilms and the detachment of cellular clusters from biofilms. These processes are of key importance for the formation of vital biofilms in vivo with the capacity of bacterial dissemination to secondary sites of infection. Recent studies showed that the phenol-soluble modulins, surfactant peptides secreted by staphylococci in a quorum-sensing controlled fashion, structure biofilms in vitro and in vivo and lead to biofilm detachment with the in vivo consequence of bacterial dissemination. These findings substantiate that quorum sensing and surfactants have widespread importance for biofilm maturation processes in bacteria and establish a novel theory of the molecular determinants driving dissemination of biofilm-associated infection.
Elevated Interleukin-6 Concentration and Alterations of the Coagulation System Are Associated with the Development of Intraventricular Hemorrhage in Extremely Preterm Infants
Authors: Poralla Christine , Hertfelder Hans-Jörg , Oldenburg Johannes , Müller Andreas , Bartmann Peter , Heep Axel
Published: August 2012

Background: Pathogenesis of intraventricular hemorrhage (IVH) in premature infants is multifactorial. Little is known about the influence of pro-inflammatory cytokine activation on the coagulation system in extremely preterm infants and its impact on the development of IVH. Objective: To determine the interaction between serum interleukin-6 (IL-6) and the coagulation system in preterm infants predisposed to the development of IVH. Methods: Vitamin K-dependent coagulation factors were examined retrospectively in 132 extremely preterm infants prior to vitamin K administration at the first day of life. Patients were grouped according to the occurrence of IVH and serum concentration of IL-6 >/<100 pg/ml. Results: Occurrence of IVH was associated with clinical diagnosis of chorioamnionitis, low gestational age, high CRIB score, air leak, catecholamine treatment, low initial hematocrit and increased serum concentration of IL-6. Infants developing IVH showed a diminished coagulation profile. Multivariable logistic regression analysis revealed decreased activity of coagulation factor VII, development of pneumothorax and low hematocrit as independent risk factors for the development of IVH. An increased IL-6 serum concentration was associated with a significantly decreased activity of coagulation factor VII and increased levels of fibrinogen. Conclusions: The association of elevated IL-6 levels with alterations of the coagulation profile and development of IVH found in our study supports the assumption of a close pathophysiological relation between inflammation and IVH.
Phylogeographic Structure and Karyotypic Diversity of the Brazilian Shrew Mouse (Blarinomys breviceps, Sigmodontinae) in the Atlantic Forest
Authors: Ventura K. , Sato-Kuwabara Y. , Fagundes V. , Geise L. , Leite Y.L.R. , Costa L.P. , Silva M.J.J. , Yonenaga-Yassuda Y. , Rodrigues M.T.
Published: August 2012

Blarinomys breviceps possesses cryptic and burrowing habits with poorly documented genetics and life history traits. Due to its rarity, only a few specimens and DNA sequences have been deposited in collections worldwide. Here, we present the most comprehensive cytogenetic and molecular characterization of this rare genus. Phylogenetic analyses based on partial cytochrome b sequences were performed, attempting to establish the relationships among individuals with distinct karyotypes along the geographic distribution of the genus in the Atlantic Forest. Classical and molecular cytogenetics, using banding patterns and FISH of telomeric and whole chromosome X-specific painting probes (obtained from the Akodontini Akodon cursor) were used to characterize and compare the chromosomal complements. Molecular phylogenetic analyses recovered 2 main geographically structured clades, northeastern and southeastern with pairwise sequence divergences among specimens varying between 4.9 and 8.4%. Eight distinct karyomorphs are described: (A) 2n = 52 (50A, XX), (B) 2n = 52 (48A, XY+2Bs), (C) 2n = 45 (42A, XY+1B), (D) 2n = 43 (37A, XX+4Bs), (E) 2n = 37 (34A, XY+1B), (F) 2n = 34 (32A, XX), (G) 2n = 31 (27A, XX+2Bs), (H) 2n = 28 (26A, XY), all with the same number of autosomal arms (FNA = 50). Variation of 0–4 supernumerary chromosomes (Bs) presenting heterogeneity in morphology and distribution of interstitial telomeric sequences (ITSs) is reported. ITSs are also found in some metacentric autosomes. The phylogeographic separation between 2 major lineages with high levels of genetic divergence, and the wide karyotypic diversity indicate that B. breviceps is a diverse group that warrants taxonomic re-evaluation.
Please Get to the Point! A Cortical Correlate of Linguistic Informativeness
Authors: Marini Andrea , Urgesi Cosimo
Published: August 2012

The production of informative messages is an effortful endeavor that relies on the interaction between microlinguistic (i.e., lexical and grammatical) and macrolinguistic (i.e., pragmatic and discourse) levels of processing. Although the neural correlates of microlinguistic processing have been extensively studied, investigation of the ability to organize the macrolinguistic aspects of message production is scanty. In this article, we show that repetitive TMS of the dorsal portion of the anterior left, but not right, inferior frontal gyrus reduces the levels of lexical informativeness and global coherence of narratives produced by healthy individuals. Interestingly, levels of productivity and microlinguistic processing were unaffected by the stimulation. These results suggest that the dorsal aspect of the anterior left inferior frontal gyrus is an epicenter of a wider neural network subserving the selection of contextually appropriate semantic representations.
Manner and Result in the Roots of Verbal Meaning
Authors: Beavers John , Koontz-Garboden Andrew
Published: August 2012

Rappaport Hovav and Levin (2010) argue that verbs fall into (at least) two classes: result verbs (e.g., break) and manner verbs (e.g., run). No verb encodes both manner and result simultaneously, a truth-conditional fact that Rappaport Hovav and Levin argue follows from how verb meanings are composed at the level of event structure. However, a key issue in verifying this claim is isolating truth-conditional diagnostics for manner and result. We develop and review a number of such diagnostics and show that there are verbs that encode both meanings together, counterexemplifying their truth-conditional complementarity. However, using evidence from scopal adverbs, we argue that when the meanings occur together, they are encoded in a single, undecomposable manner+result root at event structure. This fact validates complementarity as a fact about how many and what types of roots may occur in an event structure, though it also argues for a richer typology of roots than is typically assumed, including those encoding manner and result simultaneously.
Word Order and Scope: Transparent Interfaces and the ¾ Signature
Authors: Bobaljik Jonathan David , Wurmbrand Susi
Published: August 2012

A recurring pattern of partial correlations between word order variation and scope possibilities (the ¾ signature) supports a particular view of economy constraints in syntax, with these properties: (1) There are economy conditions (soft constraints) that value a particular type of correspondence between LF and PF representations. (2) These constraints are unidirectional: LF (broadly construed) is calculated first and determines PF (surface word order). (3) Scope rigidity is a property not of languages but of specific configurations, and the distribution of rigidity effects is (largely) predictable from independent variation in the syntactic resources of various languages.

We focus here on the interaction of these three assumptions and on the role of (2) in predicting the ¾ signature effect. We contrast our proposal with Reinhart’s (2005) Interface Economy model, in which economy conditions regulate a mapping that takes overt structure as its input and yields permissible interpretations.
Bangladeshi Women’s Political Empowerment In Urban Local Governance
Authors: Zaman Farhana
Published: August 2012

Despite notably increased female involvement in local political bodies in Bangladesh, women continue to face multifarious problems in ongoing processes of shaping political institutions. Stereotypical gendered assumptions about divisions of labour continue to discourage such women from being present and active in the political arena. The article shows that this is not just a matter of Islamic traditionality. There are other factors at work, including lack of sensitivity to such issues among female leaders. Focusing on women ward commissioners, the study reveals specifically that they are frequently unable to show their commitment to the public as they are not assigned independent wards. When women share wards with male ward commissioners, their exposure becomes somehow insignificant to the public. Fieldwork confirms that women ward commissioners firmly believe that discriminatory attitudes of their male counterparts will continue unless they are given separate wards. This supports arguments for continued affirmative action at various levels to address gender balances in South Asian politics.
The development of practising strategies in young people
Authors: Hallam Susan , Rinta Tiija , Varvarigou Maria , Creech Andrea , Papageorgi Ioulia , Gomes Teresa , Lanipekun Jennifer
Published: August 2012

There has been considerable research considering how instrumental practice changes as expertise develops. Much of that research has been relatively small scale and restricted in the range of instrumentalists included. This paper aimed to explore the development of practising strategies and motivation to practise as expertise develops with a large sample of participants at different levels of expertise playing a wide range of different instruments. A total of 3,325 young people ranging in level of expertise from beginner to the level required for entry to higher education conservatoires completed a questionnaire which consisted of a number of statements relating to practising strategies, organization of practice, and motivation to practise with a seven-point rating scale. Data were analyzed in relation to nine levels of expertise. Factor analysis revealed seven factors: adoption of systematic practice strategies; organization of practice; use of recordings for listening and feedback and use of the metronome; use of analytic strategies; adoption of ineffective strategies; concentration; and immediate correction of errors. There were statistically significant linear relationships between grade level and four of the factors but not for organization of practice; use of analytic strategies; and concentration. The findings are discussed in relation to the educational implications.
Bodily movement and facial actions in expressive musical performance by solo and duo instrumentalists: Two distinctive case studies
Authors: Davidson Jane W.
Published: August 2012

The research literature concerning gesture in musical performance increasingly reports that musically communicative and meaningful performances contain highly expressive bodily movements. These movements are involved in the generation of the musically expressive performance, but enquiry into the development of expressive bodily movement has been limited. In two studies this paper explores the expressive components of bodily movement in both solo and ensemble musical performance. The first study examined flute and clarinet performers in both solo and duo settings. Whilst each player had a specific way of expressing musical goals through their bodily movement, there were features common to the woodwind instruments investigated. Detailed analyses revealed that, although many movements were possible, performers used only six basic expressive gesture types. The second study described a performance of the internationally celebrated pianist, Lang Lang, focusing on the relationship between musical affect, bodily movement and facial expression. Analysis also revealed extensive and striking use of combined bodily and facial expression, which were involved in articulating structural features of the music and the narrative of the work. Findings suggest the existence of a repertoire of expressive information used for the generation of expressive ideas, and available to the observers of music performers.
Role behavior: A neurosociological perspective
Authors: Shkurko Aleksandr
Published: August 2012

Recent advances in social neuroscience show that many social phenomena can be traced back to neural processes. Major limitations and contributions of social neuroscience for a better understanding of social phenomena are considered. Social neuroscience is currently guided primarily by psychological notions and theories, thus making it inappropriate for solving sociological problems. Brain research for sociology can be increasingly useful within a branch we call neurosociology. Incorporation of data from cognitive and neuroscience may clarify the low-level structure of social phenomena and contribute to our understanding of social mechanisms. The notion of social status/role is taken as a possible subject of neurosociological research. A number of low-level brain structures and processes are shown to be relevant for the sociological notion of status/role. Examples include findings concerning the possible role of mirror neurons and oxytocin in social cognition and behavior. The idea of modularity is considered as a source of particular neurosociological hypothesis. It is also argued that the study of the neural system may contribute to a better understanding of social categorization, stratification and other macrosociological questions.
Serious Economics and Simple Books
Authors: Singh Gurbachan
Published: August 2012

Simple but serious books have an important role to play. So Krugman’s book on ‘depression’ is very welcome. The emphasis of this book is on unemployment (and distribution more generally, including high compensation for finance ‘experts’). The analysis is primarily Keynesian, left-leaning, ‘non-German’, and angry. Krugman argues that expansionary policies will work without endangering financial stability and that there is no need to shed tears on possible (nay, strongly recommended) higher inflation and depreciation of the currency. He advocates non-transparent default on public debt in real terms through higher inflation. Though he is very critical of Efficient Market Hypothesis, he is silent on advances in behavioural finance. We will inter-alia reconsider irrationality, consumer protection, implicit tax-subsidy in low interest rates, and detailed do’s and don’ts relative to higher capital and liquidity with banks. The book is strongly recommended—even for serious researchers and for republicans.
A Systematic Review of Qualitative Studies Exploring the Experience of Parents Whose Child Is Diagnosed and Treated for Cancer
Authors: Gibbins Jonathan , Steinhardt Karen , Beinart Helen
Published: August 2012

A growing body of research has investigated the experiences of parents of children treated for cancer. Until recently, a qualitative review has not been possible because of the lack of qualitative studies in this area. However, this has changed in recent years. The purpose of this systematic review is to summarize the findings from qualitative studies on the experiences of mothers and fathers from different countries and cultures. Twenty-eight qualitative studies were found to meet the inclusion criteria for this review. Key findings included the parents’ desire to feel in control, the need to continuously adjust to the unpredictable nature of cancer treatment, the adoption of various coping styles, emotional and practical support being valued, and gender and cultural differences being reported. Clinical implications include the need for health care professionals to provide clear information and aid the sense of control, care to be individualized with gender and cultural backgrounds taken into account, and fathers’ needs to be acknowledged and met. Other implications for clinical practice and future research are discussed.
Creating a New Community of Support for Students With Food Allergies
Authors: Pistiner Michael , Lee John J.
Published: August 2012

Managing food allergies in schools is a necessary but complex task. Breakdowns in implementation of school policies have resulted in devastating consequences and can create a divided school community. School nurses play the central role in the food allergy education of staff, parents and students. An educated school community can then be united in supporting children with food allergies. A thoughtful approach that takes these different members of the school community into consideration is essential to put a successful food allergy policy into action. This article outlines issues to consider when educating each specific group as well as discussing the challenges that can hamper school community–wide education and their potential solutions. The ultimate goal of food allergy management education is to create a community of support and to create a self-sustaining environment of understanding and awareness that may save time, decrease divisiveness, and even save a life.
Detection of IS6110 and HupB gene sequences of Mycobacterium tuberculosis and bovisin the aortic tissue of patients with Takayasu’s arteritis
Authors: Soto María Elena , Del Carmen Ávila-Casado Ma , Huesca-Gómez Claudia , Alarcon Gilberto Vargas , Castrejon Vicente , Soto Virgilia , Hernandez Sergio , Espinola-Zavaleta Nilda , Vallejo Maite , Reyes Pedro A , Gamboa Ricardo
Published: August 2012

Background

Takayasu’s arteritis (TA) is a chronic inflammatory disease affecting the large arteries and their branches; its etiology is still unknown. In individuals suffering from TA, arterial inflammation progresses to stenosis and/or occlusion, leading to organ damage and affecting survival. Relation of TA with Mycobacterium tuberculosis has been known, but there have been only a few systematic studies focusing on this association. The IS6110 sequence identifies the Mycobacterium tuberculosis complex and the HupB establishes the differences between M. tuberculosis and M. bovis. Our objective was to search the presence of IS6110 and HupB genes in aorta of patients with TA.

Methods

We analyzed aorta tissues embedded in paraffin from 5760 autopsies obtained from our institution, we divided the selected samples as cases and controls; Cases: aortic tissues of individuals with Takayasu’s arteritis. Control positive: aortic tissues (with tuberculosis disease confirmed) and control negative with other disease aortic (atherosclerosis).

Results

Of 181 selected aorta tissues, 119 fulfilled the corresponding criteria for TA, TB or atherosclerosis. Thus 33 corresponded to TA, 33 to tuberculosis (TB) and 53 to atherosclerosis. The mean age was 22 ± 13, 41 ± 19, and 57 ± 10, respectively. IS6110 and HupB sequences were detected in 70% of TA tissues, 82% in tuberculosis, and in 32% with atherosclerosis. Important statistical differences between groups with TA, tuberculosis versus atherosclerosis (p = 0.004 and 0.0001, respectively) were found.

Conclusion

We identified a higher frequency of IS6110 and HupB genes in aortic tissues of TA patients. This data suggests that arterial damage could occur due to previous infection with M. tuberculosis.
Chronic kidney disease in the type 2 diabetic patients: prevalence and associated variables in a random sample of 2642 patients of a Mediterranean area
Authors: Coll-de-Tuero Gabriel , Mata-Cases Manel , Rodriguez-Poncelas Antonio , Pepió Josep MA , Roura Pilar , Benito Belen , Franch-Nadal Josep , Saez Marc
Published: August 2012

Background

Kidney disease is associated with an increased total mortality and cardiovascular morbimortality in the general population and in patients with Type 2 diabetes. The aim of this study is to determine the prevalence of kidney disease and different types of renal disease in patients with type 2 diabetes (T2DM).

Methods

Cross-sectional study in a random sample of 2,642 T2DM patients cared for in primary care during 2007. Studied variables: demographic and clinical characteristics, pharmacological treatments and T2DM complications (diabetic foot, retinopathy, coronary heart disease and stroke). Variables of renal function were defined as follows: 1) Microalbuminuria: albumin excretion rate & 30 mg/g or 3.5 mg/mmol, 2) Macroalbuminuria: albumin excretion rate & 300 mg/g or 35 mg/mmol, 3) Kidney disease (KD): glomerular filtration rate according to Modification of Diet in Renal Disease < 60 ml/min/1.73 m2 and/or the presence of albuminuria, 4) Renal impairment (RI): glomerular filtration rate < 60 ml/min/1.73 m2, 5) Nonalbuminuric RI: glomerular filtration rate < 60 ml/min/1.73 m2 without albuminuria and, 5) Diabetic nephropathy (DN): macroalbuminuria or microalbuminuria plus diabetic retinopathy.

Results

The prevalence of different types of renal disease in patients was: 34.1% KD, 22.9% RI, 19.5% albuminuria and 16.4% diabetic nephropathy (DN). The prevalence of albuminuria without RI (13.5%) and nonalbuminuric RI (14.7%) was similar. After adjusting per age, BMI, cholesterol, blood pressure and macrovascular disease, RI was significantly associated with the female gender (OR 2.20; CI 95% 1.86–2.59), microvascular disease (OR 2.14; CI 95% 1.8–2.54) and insulin treatment (OR 1.82; CI 95% 1.39–2.38), and inversely associated with HbA1c (OR 0.85 for every 1% increase; CI 95% 0.80–0.91). Albuminuria without RI was inversely associated with the female gender (OR 0.27; CI 95% 0.21–0.35), duration of diabetes (OR 0.94 per year; CI 95% 0.91–0.97) and directly associated with HbA1c (OR 1.19 for every 1% increase; CI 95% 1.09–1.3).

Conclusions

One-third of the sample population in this study has KD. The presence or absence of albuminuria identifies two subgroups with different characteristics related to gender, the duration of diabetes and metabolic status of the patient. It is important to determine both albuminuria and GFR estimation to diagnose KD.
Prevalence of metabolic syndrome (MetS) in Chinese subjects gradually increased with impaired glucose homeostasis: a multicenter, clinical based, cross-sectional study
Authors: Xiang Yufei , Huang Gan , Zhou Weidong , Che Zhihong , Zhou Pengcheng , Zhou Zhiguang
Published: August 2012

Background

Metabolic Syndrome (MetS) is a high risk factor for Cardiovascular Diseases (CVD). We estimated to investigate how MetS prevalence by glucose homeostasis varies across different age and gender groups.

Methods

We studied 9257 Chinese subjects over the age of 15 years in two cross-sectional surveys in 2006. With oral glucose tolerance test (OGTT) test, 2341 subjects were normal glucose tolerance (NGT), and 5448 were diagnosed as having type 2 diabetes (T2D). All other 1468 subjects were considered to be impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) subjects. Diabetes was diagnosis by WHO99 criteria. We used modified NCEP-III criteria for the diagnosis of MetS.

Results

The prevalences of MetS in the male NGT, IFG/IGT and T2D groups were 25.9% (404/1559), 65.6% (769/1172), and 73.5% (2483/3376), respectively. The prevalences of MetS in the female NGT, IFG/IGT and T2D groups were 13.4% (105/782), 51.0% (151/296), and 75.4% (1563/2072), respectively. The prevalence of MetS in the male IFG/IGT group gradually decreased from 73.26% to 41.08% in subjects over the age of 30 years. The prevalence of MetS in the female IFG/IGT group gradually increased from 30% to 75% with aging.

Conclusions

The prevalence of MetS in subjects with different glucose tolerances in China was high and gradually increased with impaired glucose homeostasis both in males and females.
Molecular cloning and functional characterization of an ATP-binding cassette transporter OtrC from Streptomyces rimosus
Authors: Yu Lan , Yan Xiangyun , Wang Long , Chu Ju , Zhuang Yingping , Zhang Siliang , Guo Meijin
Published: August 2012

Background

The otrC gene of Streptomyces rimosus was previously annotated as an oxytetracycline (OTC) resistance protein. However, the amino acid sequence analysis of OtrC shows that it is a putative ATP-binding cassette (ABC) transporter with multidrug resistance function. To our knowledge, none of the ABC transporters in S. rimosus have yet been characterized. In this study, we aimed to characterize the multidrug exporter function of OtrC and evaluate its relevancy to OTC production.

Results

In order to investigate OtrC’s function, otrC is cloned and expressed in E. coli The exporter function of OtrC was identified by ATPase activity determination and ethidium bromide efflux assays. Also, the susceptibilities of OtrC-overexpressing cells to several structurally unrelated drugs were compared with those of OtrC-non-expressing cells by minimal inhibitory concentration (MIC) assays, indicating that OtrC functions as a drug exporter with a broad range of drug specificities. The OTC production was enhanced by 1.6-fold in M4018 (P = 0.000877) and 1.4-fold in SR16 (P = 0.00973) duplication mutants, while it decreased to 80% in disruption mutants (P = 0.0182 and 0.0124 in M4018 and SR16, respectively).

Conclusions

The results suggest that OtrC is an ABC transporter with multidrug resistance function, and plays an important role in self-protection by drug efflux mechanisms. This is the first report of such a protein in S. rimosus, and otrC could be a valuable target for genetic manipulation to improve the production of industrial antibiotics.
A novel, lactase-based selection and strain improvement strategy for recombinant protein expression in Kluyveromyces lactis
Authors: Krijger Jorrit-Jan , Baumann Jan , Wagner Melanie , Schulze Katja , Reinsch Christian , Klose Thomas , Onuma Osita F , Simon Claudia , Behrens Sven-Erik , Breunig Karin D
Published: August 2012

Background

The Crabtree-negative yeast species Kluyveromyces lactis has been established as an attractive microbial expression system for recombinant proteins at industrial scale. Its LAC genes allow for utilization of the inexpensive sugar lactose as a sole source of carbon and energy. Lactose efficiently induces the LAC4 promoter, which can be used to drive regulated expression of heterologous genes. So far, strain manipulation of K. lactis by homologous recombination was hampered by the high rate of non-homologous end-joining.

Results

Selection for growth on lactose was applied to target the insertion of heterologous genes downstream of the LAC4 promoter into the K. lactis genome and found to yield high numbers of positive transformants. Concurrent reconstitution of the β-galactosidase gene indicated the desired integration event of the expression cassette, and β-galactosidase activity measurements were used to monitor gene expression for strain improvement and fermentation optimization. The system was particularly improved by usage of a cell lysis resistant strain, VAK367-D4, which allowed for protein accumulation in long-term fermentation. Further optimization was achieved by increased gene dosage of KlGAL4 encoding the activator of lactose and galactose metabolic genes that led to elevated transcription rates. Pilot experiments were performed with strains expressing a single-chain antibody fragment (scFvox) and a viral envelope protein (BVDV-E2), respectively. scFvox was shown to be secreted into the culture medium in an active, epitope-binding form indicating correct processing and protein folding; the E2 protein could be expressed intracellularly. Further data on the influence of protein toxicity on batch fermentation and potential post-transcriptional bottlenecks in protein accumulation were obtained.

Conclusions

A novel Kluyveromyces lactis host-vector system was developed that places heterologous genes under the control of the chromosomal LAC4 promoter and that allows monitoring of its transcription rates by β-galactosidase measurement. The procedure is rapid and efficient, and the resulting recombinant strains contain no foreign genes other than the gene of interest. The recombinant strains can be grown non-selectively in rich medium and stably maintained even when the gene product exerts protein toxicity.
Deaths due to Plasmodium knowlesi malaria in Sabah, Malaysia: association with reporting as Plasmodium malariae and delayed parenteral artesunate
Authors: Rajahram Giri S , Barber Bridget E , William Timothy , Menon Jayaram , Anstey Nicholas M , Yeo Tsin W
Published: August 2012

Background

The simian parasite Plasmodium knowlesi is recognized as a common cause of severe and fatal human malaria in Sabah, Malaysia, but is morphologically indistinguishable from and still commonly reported as Plasmodium malariae, despite the paucity of this species in Sabah. Since December 2008 Sabah Department of Health has recommended intravenous artesunate and referral to a general hospital for all severe malaria cases of any species. This paper reviews all malaria deaths in Sabah subsequent to the introduction of these measures. Reporting of malaria deaths in Malaysia is mandatory.

Methods

Details of reported malaria deaths during 2010-2011 were reviewed to determine the proportion of each Plasmodium species. Demographics, clinical presentations and management of severe malaria caused by each species were compared.

Results

Fourteen malaria deaths were reported, comprising seven Plasmodium falciparum, six P. knowlesi and one Plasmodium vivax (all PCR-confirmed). Of the six P. knowlesi deaths, five were attributable to knowlesi malaria and one was attributable to P. knowlesi-associated enterobacter sepsis. Patients with directly attributable P. knowlesi deaths (N = 5) were older than those with P. falciparum (median age 51 [IQR 50-65] vs 22 [IQR 9-55] years, p = 0.06). Complications in fatal P. knowlesi included respiratory distress (N = 5, 100%), hypotension (N = 4, 80%), and renal failure (N = 4, 80%). All patients with P. knowlesi were reported as P. malariae by microscopy. Only two of five patients with severe knowlesi malaria on presentation received immediate parenteral anti-malarial treatment. The patient with P. vivax-associated severe illness did not receive parenteral treatment. In contrast six of seven patients with severe falciparum malaria received immediate parenteral treatment.

Conclusion

Plasmodium knowlesi was responsible, either directly or through gram-negative bacteraemia, for almost half of malaria deaths in Sabah. Patients with severe non-falciparum malaria were less likely to receive immediate parenteral therapy. This highlights the need in Sabah for microscopically diagnosed P. malariae to be reported as P. knowlesi to improve recognition and management of this potentially fatal species. Clinicians need to be better informed of the potential for severe and fatal malaria from non-falciparum species, and the need to treat all severe malaria with immediate intravenous artesunate.
The extravascular compartment of the bone marrow: a niche for Plasmodium falciparum gametocyte maturation?
Authors: Farfour Eric , Charlotte Frédéric , Settegrana Catherine , Miyara Makoto , Buffet Pierre
Published: August 2012

Background

Plasmodium falciparum immature gametocytes accumulate in the bone marrow, but their exact location in this tissue remains unclear.

Methods

The stage and deposition pattern of gametocytes was analysed on histological sections of a bone marrow sample collected in a patient with subacute P. falciparum malaria.

Results

A majority (89%) of immature stages II to IV gametocytes and a minority (29%) of mature stage V gametocytes were observed in extravascular spaces.

Discussion and conclusion

These observations represent a valuable step towards understanding sequestration patterns of P. falciparum gametocytes and may ultimately lead to novel transmission-blocking interventions.
IFN-γ-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments
Authors: Vardjan Nina , Gabrijel Mateja , Potokar Maja , Švajger Urban , Kreft Marko , Jeras Matjaž , de Pablo Yolanda , Faiz Maryam , Pekny Milos , Zorec Robert
Published: August 2012

Background

In immune-mediated diseases of the central nervous system, astrocytes exposed to interferon-γ (IFN-γ) can express major histocompatibility complex (MHC) class II molecules and antigens on their surface. MHC class II molecules are thought to be delivered to the cell surface by membrane-bound vesicles. However, the characteristics and dynamics of this vesicular traffic are unclear, particularly in reactive astrocytes, which overexpress intermediate filament (IF) proteins that may affect trafficking. The aim of this study was to determine the mobility of MHC class II vesicles in wild-type (WT) astrocytes and in astrocytes devoid of IFs.

Methods

The identity of MHC class II compartments in WT and IF-deficient astrocytes 48 h after IFN-γ activation was determined immunocytochemically by using confocal microscopy. Time-lapse confocal imaging and Alexa Fluor546-dextran labeling of late endosomes/lysosomes in IFN-γ treated cells was used to characterize the motion of MHC class II vesicles. The mobility of vesicles was analyzed using ParticleTR software.

Results

Confocal imaging of primary cultures of WT and IF-deficient astrocytes revealed IFN-γ induced MHC class II expression in late endosomes/lysosomes, which were specifically labeled with Alexa Fluor546-conjugated dextran. Live imaging revealed faster movement of dextran-positive vesicles in IFN-γ-treated than in untreated astrocytes. Vesicle mobility was lower in IFN-γ-treated IF-deficient astrocytes than in WT astrocytes. Thus, the IFN-γ-induced increase in the mobility of MHC class II compartments is IF-dependent.

Conclusions

Since reactivity of astrocytes is a hallmark of many CNS pathologies, it is likely that the up-regulation of IFs under such conditions allows a faster and therefore a more efficient delivery of MHC class II molecules to the cell surface. In vivo, such regulatory mechanisms may enable antigen-presenting reactive astrocytes to respond rapidly and in a controlled manner to CNS inflammation.
Pathological femoral fractures due to osteomalacia associated with adefovir dipivoxil treatment for hepatitis B: a case report
Authors: Tanaka Motoyuki , Setoguchi Takao , Ishidou Yasuhiro , Arishima Yoshiya , Hirotsu Masataka , Saitoh Yoshinobu , Nakamura Shunsuke , Kakoi Hironori , Nagano Satoshi , Yokouchi Masahiro , Kamizono Junichi , Komiya Setsuro
Published: August 2012

We present a case of a 62-year-old man who underwent total hip arthroplasty for treatment of pathologic femoral neck fracture associated with adefovir dipivoxil-induced osteomalacia. He had a 13-month history of bone pain involving his shoulders, hips, and knee. He received adefovir dipivoxil for treatment of lamivudine-resistant hepatitis B virus infection for 5 years before the occurrence of femoral neck fracture. Orthopedic surgeons should be aware of osteomalacia and pathological hip fracture caused by drug-induced renal dysfunction, which results in Fanconi’s syndrome.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1600344696739249
Mass spectrometry quantification of clusterin in the human brain
Authors: Chen Junjun , Wang Meiyao , Turko Illarion V
Published: August 2012

Background

The multifunctional glycoprotein clusterin has been associated with late-onset Alzheimer’s disease (AD). Further investigation to define the role of clusterin in AD phenotypes would be aided by the development of techniques to quantify level, potential post-translational modifications, and isoforms of clusterin. We have developed a quantitative technique based on multiple reaction monitoring (MRM) mass spectrometry to measure clusterin in human postmortem brain tissues.

Results

A stable isotope-labeled concatenated peptide (QconCAT) bearing selected peptides from clusterin was expressed with an in vitro translation system and purified. This clusterin QconCAT was validated for use as an internal standard for clusterin quantification using MRM mass spectrometry. Measurements were performed on the human postmortem frontal and temporal cortex from control and severe AD cases. During brain tissues processing, 1% SDS was used in the homogenization buffer to preserve potential post-translational modifications of clusterin. However, MRM quantifications in the brain did not suggest phosphorylation of Thr393, Ser394, and Ser396 residues reported for clusterin in serum. MRM quantifications in the frontal cortex demonstrated significantly higher (P < 0.01) level of clusterin in severe AD group (39.1 ± 9.1 pmol/mg tissue protein) in comparison to control group (25.4 ± 4.4 pmol/mg tissue protein). In the temporal cortex, the clusterin levels were not significantly different, 29.0 ± 7.9 pmol/mg tissue protein and 28.0 ± 8.4 pmol/mg tissue protein in control and severe AD groups, respectively.

Conclusions

The proposed protocol is a universal quantitative technique to assess expression level of clusterin. It is expected that application of this protocol to quantification of various clusterin isoforms and potential post-translational modifications will be helpful in addressing the role of clusterin in AD.
Flexibility of EF-hand motifs: structural and thermodynamic studies of Calcium Binding Protein-1 from Entamoeba histolytica with Pb2+, Ba2+, and Sr2+
Authors: Kumar Shivesh , Ahmad Ejaz , Kumar Sanjeev , Khan Rizwan Hasan , Gourinath Samudrala
Published: August 2012

Background

EF-hand proteins can be activated by the binding of various heavy metals other than calcium, and such complexes can disturb the calcium-signaling pathway and cause toxicity and disease causing state. So far, no comprehensive study has been done to understand different heavy metals binding to calcium signaling proteins.

Results

In this work, the flexibility of the EF-hand motifs are examined by crystallographic and thermodynamic studies of binding of Pb2+, Ba2+ and Sr2+ to Calcium Binding Protein-1 from Entamoeba histolytica (EhCaBP1). The structures of the EhCaBP1- heavy metal complexes are found to be overall similar, nevertheless specific differences in metal coordination, and small differences in the coordination distances between the metal and the ligands in the metal binding loop. The largest such distances occur for the Ba2+- EhCaBP1 complex, where two bariums are bound with partial occupancy at the EF2 motif. Thermodynamic studies confirm that EhCaBP1 has five binding sites for Ba2+ compared to four binding sites for the other metals. These structures and thermodynamic studies reveal that the EF-hand motifs can accommodate several heavy atoms with similar binding affinities. The binding of Ca2+ to the 1st, 2nd and 4th sites and the binding of Ba2+ to the 1st, 2nd, 4th and 5th sites are both enthalpically and entropically driven, whereas the binding of Sr2+ to the 1st, 2nd and 4th sites are simply enthalpy driven, interestingly in agreement with ITC data, Sr2+ do not coordinate with water in this structure. For all the metals, binding to the 3rd site is only entropy driven.

Conclusion

Energetically, Ca2+ is preferred in three sites, while in one site Ba2+ has better binding energy. The Sr2+-coordination in the EF hand motifs is similar to that of the native Ca2+ bound structure, except for the lack of water coordination. Sr2+ coordination seems to be a pre-formed in nature since all seven coordinating atoms are from the protein itself, which also correlates with entropy contributions in Sr2+ binding. These findings improve our understanding of metal association with calcium binding proteins and of metal induced conformational changes.
Gene-expression profiling of microdissected breast cancer microvasculature identifies distinct tumor vascular subtypes
Authors: Pepin François , Bertos Nicholas , Laferrière Julie , Sadekova Svetlana , Souleimanova Margarita , Zhao Hong , Finak Greg , Meterissian Sarkis , Hallett Michael T , Park Morag
Published: August 2012

Introduction

Angiogenesis represents a potential therapeutic target in breast cancer. However, responses to targeted antiangiogenic therapies have been reported to vary among patients. This suggests that the tumor vasculature may be heterogeneous and that an appropriate choice of treatment would require an understanding of these differences.

Methods

To investigate whether and how the breast tumor vasculature varies between individuals, we isolated tumor-associated and matched normal vasculature from 17 breast carcinomas by laser-capture microdissection, and generated gene-expression profiles. Because microvessel density has previously been associated with disease course, tumors with low (n = 9) or high (n = 8) microvessel density were selected for analysis to maximize heterogeneity for this feature.

Results

We identified differences between tumor and normal vasculature, and we describe two subtypes present within tumor vasculature. These subtypes exhibit distinct gene-expression signatures that reflect features including hallmarks of vessel maturity. Potential therapeutic targets (MET, ITGAV, and PDGFRβ) are differentially expressed between subtypes. Taking these subtypes into account has allowed us to derive a vascular signature associated with disease outcome.

Conclusions

Our results further support a role for tumor microvasculature in determining disease progression. Overall, this study provides a deeper molecular understanding of the heterogeneity existing within the breast tumor vasculature and opens new avenues toward the improved design and targeting of antiangiogenic therapies.
Tax Reform: Theory and Practice
Authors: Pechman Joseph A
Published: August 2012

The Tax Reform Act of 1986 is the most significant piece of tax legislation enacted since the income tax was converted to a mass tax during World War II. After decades of erosion, the individual and corporate income tax bases were broadened and the revenues were used to reduce tax rates. Loopholes and preferences that were formerly considered sacrosanct were eliminated or moderated despite the determined opposition of powerful pressure groups. Comprehensive income taxation, which had earlier been regarded as an impossible dream, carried the day with strong bipartisan support. I will trace the origins of the tax reform movement and speculate about why it was successful in 1986 after repeated failures in earlier years. I also explain what the 1986 act accomplished and what more needs to be done to achieve the objectives of comprehensive income taxation.
Antitrust and Merger Policy: A Review and Critique
Authors: White Lawrence J
Published: August 2012

This review will consider the Department of Justice Merger Guidelines of the 1980s, discussing market definition, market share concentration and entry conditions, consideration of other market characteristics, and cost efficiencies. It will also assess the application of the guidelines in practice. The merger guidelines are certainly not perfect, nor have they been applied perfectly. But they represent an important advance over that which preceded them, and they represent an exceedingly sensible way to think about merger enforcement and especially about market definition in a merger context. Policy has surely improved as a consequence of their development and application.
In Honor of Nobel Laureate, Franco Modigliani
Authors: Merton Robert C
Published: August 2012

When Gary Becker asked me to introduce Franco Modigliani on this occasion celebrating Franco's Nobel Prize, he noted that, by tradition, the honoree does not speak. It is the introducer who speaks, devoting 30 minutes or so to the laureate's chief contributions to economics. Now, I know of no meeting of economists attended by Franco where he didn't speak. But this occasion is designed to do Franco Modigliani honor, rather than delegate him to perform still another feat of critical summary for the enduring benefit of his fellow economists. Where shall I begin? Franco Modigliani is a great macroeconomist. He is also a great microeconomist. Still, it is the composite of theoretical, empirical, applied, and policy-oriented work that provides the unmistakable Franco Modigliani stamp. In the parlance of corporate finance, he is a complete, horizontally and vertically integrated, economic-research system.
Anomalies: Seasonal Movements in Security Prices II: Weekend, Holiday, Turn of the Month, and Intraday Effects
Authors: Thaler Richard
Published: August 2012

This feature will report successful searches for disconfirming evidence--economic anomalies. As suggested by Thomas Kuhn, an economic anomaly is a result inconsistent with the economics paradigm. Economics is distinguished from other social sciences by the belief that most (all?) behavior can be explained by assuming that agents have stable, well-defined preferences and make rational choices consistent with those preferences in markets that (eventually) clear. An empirical result is anomalous if it is difficult to “rationalize,” or if implausible assumptions are necessary to explain it within the paradigm. In the previous issue, I reviewed the peculiar behavior of security prices in January. Stock prices tend to rise in January, particularly the prices of small firms and firms whose stock price has declined substantially over the past few years. Also, risky stocks earn most of their risk premiums in January. This issue will conclude our survey of seasonal anomalies in security prices with a review of four additional effects: the behavior of prices over weekends, before holidays, at the turn of each month, and within the day.