bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey of doctors' opinions of the legalisation of physician assisted suicide
Authors: Lee William , Price Annabel , Rayner Lauren , Hotopf Matthew
Published: April 2009

Background

Assisted dying has wide support among the general population but there is evidence that those providing care for the dying may be less supportive. Senior doctors would be involved in implementing the proposed change in the law. We aimed to measure support for legalising physician assisted dying in a representative sample of senior doctors in England and Wales, and to assess any association between doctors' characteristics and level of support for a change in the law.

Methods

We conducted a postal survey of 1000 consultants and general practitioners randomly selected from a commercially available database. The main outcome of interest was level of agreement with any change in the law to allow physician assisted suicide.

Results

The corrected participation rate was 50%. We analysed 372 questionnaires. Respondents' views were divided: 39% were in favour of a change to the law to allow assisted suicide, 49% opposed a change and 12% neither agreed nor disagreed. Doctors who reported caring for the dying were less likely to support a change in the law. Religious belief was also associated with opposition. Gender, specialty and years in post had no significant effect.

Conclusion

More senior doctors in England and Wales oppose any step towards the legalisation of assisted dying than support this. Doctors who care for the dying were more opposed. This has implications for the ease of implementation of recently proposed legislation.
Evaluation of anti-IL-6 monoclonal antibody therapy using murine type II collagen-induced arthritis
Authors: Liang Bailin , Song Zheng , Wu Bin , Gardner Debra , Shealy David , Song Xiao-Yu , Wooley Paul H
Published: April 2009

Interleukin-6 is a multifunctional cytokine that is critical for T/B-cell differentiation and maturation, immunoglobulin secretion, acute-phase protein production, and macrophage/monocyte functions. Extensive research into the biology of IL-6 has implicated IL-6 in the pathophysiology and pathogenesis of RA. An anti-murine IL-6 mAb that neutralizes mouse IL-6 activities was tested in animal model of collagen-induced arthritis. Prophylactic treatment with anti-IL-6 mAb significantly reduced the incidence and severity of arthritis compared to control mAb treated mice. The mitogenic response of B and T cells isolated from the lymph nodes of anti-IL-6 treated mice was significantly reduced compared to cells isolated from control mAb treated mice. The overall histopathology score for paws from the anti-IL-6 treated mice was significantly reduced when compared to paws from mice treated with control mAb, including both inflammatory (synovitis and pannus) and erosive (erosions and architecture) parameters. Reduced loss of cartilage matrix components was also observed in the anti-IL-6 treated mice. Collectively, these data suggest that IL-6 plays a major role in the pathophysiology of rheumatoid arthritis, and thus support the potential benefit of anti-IL-6 mAb treatment in rheumatoid arthritis patients.
Synchronous infiltrating ductal carcinoma and primary extramedullary plasmacytoma of the breast
Authors: Cao Shui , Kang Hong-Gang , Liu Yan-Xue , Ren Xiu-Bao
Published: April 2009

Background

Extramedullary plasmacytomas are seldom solitary and usually progress to diffuse myelomatosis. Plasmacytomas of the breast are rare, especially when not associated multiple myeloma. Synchronous infiltrating ductal carcinoma and primary extramedullary plasmacytoma of the breast have not previously reported.

Case presentation

A 27-years-old woman with an untreated upper outer quadrant breast mass for 1-year was referred to our cancer hospital for surgical evaluation of increasing breast pain. Postoperatively, microscopic examination revealed an infiltrating ductal carcinoma complicated by an extramedullary plasmacytoma divided by fibrous tissue in one section. Following surgery, the patient received chemotherapy for the carcinoma and radiotherapy for the plasmacytoma.

Conclusion

In this case, careful histopathology examination was essential to make the correct diagnosis and therapy for these synchronous lesions. The patient finished chemotherapy and radiotherapy without significant adverse effects.
The roles of ASK family proteins in stress responses and diseases
Authors: Hattori Kazuki , Naguro Isao , Runchel Christopher , Ichijo Hidenori
Published: April 2009

Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase kinase family, which activates c-Jun N-terminal kinase and p38 in response to a diverse array of stresses such as oxidative stress, endoplasmic reticulum stress and calcium influx. In the past decade, various regulatory mechanisms of ASK1 have been elucidated, including its oxidative stress-dependent activation. Recently, it has emerged that ASK family proteins play key roles in cancer, cardiovascular diseases and neurodegenerative diseases. In this review, we summarize the recent findings on ASK family proteins and their implications in various diseases.
Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis
Authors: Riordan Neil H , Ichim Thomas E , Min Wei-Ping , Wang Hao , Solano Fabio , Lara Fabian , Alfaro Miguel , Rodriguez Jorge Paz , Harman Robert J , Patel Amit N , Murphy Michael P , Lee Roland R , Minev Boris
Published: April 2009

The stromal vascular fraction (SVF) of adipose tissue is known to contain mesenchymal stem cells (MSC), T regulatory cells, endothelial precursor cells, preadipocytes, as well as anti-inflammatory M2 macrophages. Safety of autologous adipose tissue implantation is supported by extensive use of this procedure in cosmetic surgery, as well as by ongoing studies using in vitro expanded adipose derived MSC. Equine and canine studies demonstrating anti-inflammatory and regenerative effects of non-expanded SVF cells have yielded promising results. Although non-expanded SVF cells have been used successfully in accelerating healing of Crohn's fistulas, to our knowledge clinical use of these cells for systemic immune modulation has not been reported. In this communication we discuss the rationale for use of autologous SVF in treatment of multiple sclerosis and describe our experiences with three patients. Based on this rationale and initial experiences, we propose controlled trials of autologous SVF in various inflammatory conditions.
The design and protocol of acupuncture for migraine prophylaxis: A multicenter randomized controlled trial
Authors: Zhang Yan , Wang Linpeng , Liu Huilin , Li Nan , Li Jingdao , Yi Jinghong
Published: April 2009

Background

Many studies have already reported encouraging results in the prophylactic therapy of migraine by acupuncture, but there seems to be a lack of high quality randomized controlled trials from China. We design and perform a randomized controlled clinical trial to evaluate the efficacy of acupuncture compared with flunarizine in the prophylactic therapy of patients with migraine without aura in China.

Methods

This trial is a multicenter, prospective, randomized controlled clinical trial. The 140 migraine patients are randomly allocated to two different groups. The acupuncture groups (n = 70) is treated with acupuncture and placebo medicine; while the control group (n = 70) is treated with sham acupuncture and medicine (Flunarizine). Both Flunarizine and placebo are taken 10 mg once per night for the first 2 weeks and then 5 mg once per night for the next 2 weeks. Patients in both groups receive 12 sessions of verum/sham acupuncture in 4 weeks.

Discussion

The study design and the long term clinical practice of acupuncturists guarantee a high external validity for the results. The results of our trial will be helpful to supply the evidence on the efficacy of acupuncture for migraine prophylaxis in China.

Trial Registration

The trial is registered at Controlled Clinical Trials: ISRCTN49839714.
Interaction of hookworm 14-3-3 with the forkhead transcription factor DAF-16 requires intact Akt phosphorylation sites
Authors: Kiss Joshua E , Gao Xin , Krepp Joseph M , Hawdon John M
Published: April 2009

Background

Third-stage infective larvae (L3) of hookworms are in an obligatory state of developmental arrest that ends upon entering the definitive host, where they receive a signal that re-activates development. Recovery from the developmentally arrested dauer stage ofCaenorhabditis elegansis analogous to the resumption of development during hookworm infection. Insulin-like signaling (ILS) mediates recovery from arrest inC. elegansand activation of hookworm dauer L3. InC. elegans, phosphorylation of the forkhead transcription factor DAF-16 in response to ILS creates binding cites for the 14-3-3 proteinCe-FTT-2, which translocates DAF-16 out of the nucleus, resulting in resumption of reproductive development.

Results

To determine if hookworm 14-3-3 proteins play a similar role in L3 activation, hookworm FTT-2 was identified and tested for its ability to interact withA. caninumDAF-16in vitro. TheAc-FTT-2 amino acid sequence was 91% identical to theCe-FTT-2, and was most closely related to FTT-2 from other nematodes.Ac-FTT-2 was expressed in HEK 293T cells, and was recognized by an antibody against human 14-3-3β isoform. Reciprocal co-immunoprecipitations using anti-epitope tag antibodies indicated thatAc-FTT-2 interacts withAc-DAF-16 when co-expressed in serum-stimulated HEK 293T cells. This interaction requires intact Akt consensus phosphorylation sites at serine107 and threonine312, but not serine381.Ac-FTT-2 was undetectable by Western blot in excretory/secretory products from serum-stimulated (activated) L3 or adultA. caninum.

Conclusion

The results indicate thatAc-FTT-2 interacts with DAF-16 in a phosphorylation-site dependent manner, and suggests thatAc-FTT-2 mediates activation of L3 by bindingAc-DAF-16 during hookworm infection.
Interleukin-1beta and fibroblast growth factor receptor 1 cooperate to induce cyclooxygenase-2 during early mammary tumourigenesis
Authors: Reed Johanna R , Leon Ronald P , Hall Majken K , Schwertfeger Kathryn L
Published: April 2009

Introduction

Inflammation within the tumour microenvironment correlates with increased invasiveness and poor prognosis in many types of cancer, including breast cancer. We have previously demonstrated that activation of a mouse mammary tumour virus (MMTV)-driven inducible fibroblast growth factor receptor 1 (iFGFR1) transgene in mammary epithelial cells results in an inflammatory response characterised by induction of inflammatory genes in the mammary gland. Specifically, we have observed increased levels of IL-1β expression in the mammary gland following activation of iFGFR1 and have used the iFGFR1 model to elucidate the function of IL-1β in promoting iFGFR1-induced mammary lesions.

Methods

To determine the functional consequences of IL-1β induction during FGFR1-induced mammary tumourigenesis, the effects of IL-1β inhibition on the formation of epithelial hyperplasias were examined using the MMTV-iFGFR1 transgenic mouse model. Further studies used a combination of the HC-11 mammary epithelial cell line that stably expresses iFGFR1 and the MMTV-iFGFR1 transgenic mice to further define the mechanisms of IL-1β function.

Results

Inhibition of IL-1β activity in vivo resulted in reduced iFGFR1-induced epithelial proliferation and formation of hyperplastic structures. Further studies demonstrated that treatment of mammary epithelial cells with IL-1β-induced expression of cyclooxygenase (Cox)-2 both in vitro and in vivo. Finally, inhibition of Cox-2 prior to activation of iFGFR1 in the transgenic mice also resulted in decreased iFGFR1-induced formation of hyperplastic structures.

Conclusions

The results from these studies indicate that targeting the inflammatory cytokine IL-1β partially inhibits iFGFR1-induced formation of early-stage mammary lesions, in part through induction of Cox-2. These findings demonstrate that activation of a growth factor receptor in mammary epithelial cells results in increased expression of inflammatory mediators, which cooperate to promote the initiation of hyperplastic lesions in the mammary gland.
The bovine lactation genome: insights into the evolution of mammalian milk
Authors: Lemay Danielle G , Lynn David J , Martin William F , Neville Margaret C , Casey Theresa M , Rincon Gonzalo , Kriventseva Evgenia V , Barris Wesley C , Hinrichs Angie S , Molenaar Adrian J , Pollard Katherine S , Maqbool Nauman J , Singh Kuljeet , Murney Regan , Zdobnov Evgeny M , Tellam Ross L , Medrano Juan F , German J Bruce , Rijnkels Monique
Published: April 2009

Background

The newly assembled Bos taurus genome sequence enables the linkage of bovine milk and lactation data with other mammalian genomes.

Results

Using publicly available milk proteome data and mammary expressed sequence tags, 197 milk protein genes and over 6,000 mammary genes were identified in the bovine genome. Intersection of these genes with 238 milk production quantitative trait loci curated from the literature decreased the search space for milk trait effectors by more than an order of magnitude. Genome location analysis revealed a tendency for milk protein genes to be clustered with other mammary genes. Using the genomes of a monotreme (platypus), a marsupial (opossum), and five placental mammals (bovine, human, dog, mice, rat), gene loss and duplication, phylogeny, sequence conservation, and evolution were examined. Compared with other genes in the bovine genome, milk and mammary genes are: more likely to be present in all mammals; more likely to be duplicated in therians; more highly conserved across Mammalia; and evolving more slowly along the bovine lineage. The most divergent proteins in milk were associated with nutritional and immunological components of milk, whereas highly conserved proteins were associated with secretory processes.

Conclusions

Although both copy number and sequence variation contribute to the diversity of milk protein composition across species, our results suggest that this diversity is primarily due to other mechanisms. Our findings support the essentiality of milk to the survival of mammalian neonates and the establishment of milk secretory mechanisms more than 160 million years ago.
Choosing the right path: enhancement of biologically relevant sets of genes or proteins using pathway structure
Authors: Thomas Reuben , Gohlke Julia M , Stopper Geffrey F , Parham Frederick M , Portier Christopher J
Published: April 2009

A method is proposed that finds enriched pathways relevant to a studied condition using the measured molecular data and also the structural information of the pathway viewed as a network of nodes and edges. Tests are performed using simulated data and genomic data sets and the method is compared to two existing approaches. The analysis provided demonstrates the method proposed is very competitive with the current approaches and also provides biologically relevant results.
Microbial co-habitation and lateral gene transfer: what transposases can tell us
Authors: Hooper Sean D , Mavromatis Konstantinos , Kyrpides Nikos C
Published: April 2009

Background

Determining the habitat range for various microbes is not a simple, straightforward matter, as habitats interlace, microbes move between habitats, and microbial communities change over time. In this study, we explore an approach using the history of lateral gene transfer recorded in microbial genomes to begin to answer two key questions: where have you been and who have you been with?

Results

All currently sequenced microbial genomes were surveyed to identify pairs of taxa that share a transposase that is likely to have been acquired through lateral gene transfer. A microbial interaction network including almost 800 organisms was then derived from these connections. Although the majority of the connections are between closely related organisms with the same or overlapping habitat assignments, numerous examples were found of cross-habitat and cross-phylum connections.

Conclusions

We present a large-scale study of the distributions of transposases across phylogeny and habitat, and find a significant correlation between habitat and transposase connections. We observed cases where phylogenetic boundaries are traversed, especially when organisms share habitats; this suggests that the potential exists for genetic material to move laterally between diverse groups via bridging connections. The results presented here also suggest that the complex dynamics of microbial ecology may be traceable in the microbial genomes.
Activation of PPARβ/δ inhibits leukocyte recruitment, cell adhesion molecule expression, and chemokine release
Authors: Piqueras Laura , Sanz Maria Jesus , Perretti Mauro , Morcillo Esteban , Norling Lucy , Mitchell Jane A , Li Yoyo , Bishop-Bailey David
Published: April 2009

Activation of the nuclear receptor PPARb/d inhibits acute inflammatory responses in vitro with human primary cells and in vivo by targeting the endothelial cell-leukocyte interaction.

The infiltration of PMNs into tissues is a prominent feature in inflammation. The mechanism underlying PMN recruitment depends on the release of chemotactic mediators and CAM expression on endothelial cells. The nuclear receptor PPARβ/δ is widely expressed in many tissues, including the vascular endothelium; however, its role in acute inflammation remains unclear. Using intravital microscopy in the mouse cremasteric microcirculation, we have shown that activation of PPARβ/δ by its selective ligand GW501516 inhibits TNF-α-induced leukocyte rolling flux, adhesion, and emigration in a dose-dependant manner. Moreover, GW501516 reduced the expression of adhesion molecules such as ICAM-1, VCAM-1, and E-selectin in the cremasteric postcapillary venules. Similarly, rolling and adhesion of hPMNs under physiological flow on TNF-α-activated HUVECs were also inhibited markedly by GW501516. These inhibitory responses of GW501516 on activated endothelium were accompanied by a reduction in TNF-α-induced endothelial GRO-α release and VCAM-1, E-selectin, and ICAM-1 mRNA expression. Taken together, our results show that PPARβ/δ modulates acute inflammation in vivo and in vitro under flow by targeting the neutrophil-endothelial cell interaction.
IL-15 protects antigen-specific CD8+ T cell contraction after Mycobacterium bovis bacillus Calmette-Guérin infection
Authors: Tang Ce , Yamada Hisakata , Shibata Kensuke , Yoshida Shin-ichi , Wajjwalku Worawidh , Yoshikai Yasunobu
Published: April 2009

In vivo administration of IL-15 at the contraction phase in BCG infection inhibited apoptosis of effector CD8+ T cells resulting in the significant increase of Ag-specific memory CD8+ T cells.

We reported previously that IL-15 plays a critical role in protecting effector CD8+ T cells from apoptosis during the contraction phase following acute infection with Listeria monocytogenes by inducing antiapoptotic molecules. In the present study, we examined the effects of in vivo administration of rIL-15 on contraction of CD8+ T cells after chronic infection with Mycobacterium bovis BCG and on the efficacy of BCG vaccination against Mycobacterium tuberculosis infection. Antigen-specific CD8+ T cells reached an expansion peak at approximately Day 21, followed by a contraction after inoculation with rBCG expressing OVA. In vivo administration of rIL-15 from Days 22 to 42 after BCG inoculation inhibited apoptosis of effector CD8+ T cells by up-regulating their Bcl-2 expression, resulting in a significant increase of antigen-specific memory CD8+ T cells producing IFN-γ. However, the IL-15 treatment did not elicit improved efficacy of BCG vaccination against M. tuberculosis. These results suggest that IL-15 plays a critical role in protecting activated CD8+ T cells from apoptosis during the contraction phase following BCG inoculation, although IL-15 administration alone at the contraction phase might not be sufficient to protect the efficient memory T cell responses against subsequent infection with M. tuberculosis.
Activin Signaling: Effects on Body Composition and Mitochondrial Energy Metabolism
Authors: Li Liunan , Shen Joseph J. , Bournat Juan C. , Huang Lihua , Chattopadhyay Abanti , Li Zhihong , Shaw Chad , Graham Brett H. , Brown Chester W.
Published: April 2009

Activin-βA and activin-βB (encoded by Inhba and Inhbb genes, respectively) are closely related TGF-β superfamily members that participate in a variety of biological processes. We previously generated mice with an insertion allele at the Inhba locus, InhbaBK. In this allele, the sequence encoding the Inhba mature domain is replaced with that of Inhbb, rendering the gene product functionally hypomorphic. Homozygous (InhbaBK/BK) and hemizygous (InhbaBK/−) mice are smaller and leaner than their wild-type littermates, and many tissues are disproportionately small relative to total body weight. To determine the mechanisms that contribute to these phenomena, we investigated the metabolic consequences of the mutation. Although the growth of InhbaBK mice is improved by providing a calorie-rich diet, diet-induced obesity, fatty liver, and insulin resistance (hallmarks of chronic caloric excess) do not develop, despite greater caloric intake than wild-type controls. Physiological, molecular, and biochemical analyses all revealed characteristics that are commonly associated with increased mitochondrial energy metabolism, with a corresponding up-regulation of several genes that reflect enhanced mitochondrial biogenesis and function. Oxygen consumption, an indirect measure of the metabolic rate, was markedly increased in InhbaBK/BK mice, and polarographic analysis of liver mitochondria revealed an increase in ADP-independent oxygen consumption, consistent with constitutive uncoupling of the inner mitochondrial membrane. These findings establish a functional relationship between activin signaling and mitochondrial energy metabolism and further support the rationale to target this signaling pathway for the medical treatment of cachexia, obesity, and diabetes.
Regulation and Function of Tissue Inhibitor of Metalloproteinase (TIMP) 1 and TIMP3 in Periovulatory Rat Granulosa Cells
Authors: Li Feixue , Curry Thomas E.
Published: April 2009

In the ovary, the matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinase (TIMPs) have been postulated to regulate extracellular matrix remodeling associated with ovulation. In the present study, we investigated the regulatory mechanisms controlling expression of Timp1 and Timp3 mRNA in periovulatory granulosa cells. Granulosa cells were isolated from immature pregnant mare serum gonadotropin-primed (10 IU) rat ovaries and treated with human chorionic gonadotropin (hCG; 1 IU/ml). At 4 h after hCG treatment, Timp1 expression was highest and then decreased gradually over the remaining 24 h of culture. In contrast, hCG induced a biphasic increase of Timp3 expression at 2 and 16 h. The hCG stimulated expression of Timp1 and Timp3 mRNA was blocked by inhibitors of the protein kinase A (H89), protein kinase C (GF109203), and MAPK (SB2035850) pathways. To further explore Timp1 and Timp3 regulation, cells were cultured with the progesterone receptor antagonist RU486, which blocked the hCG induction of Timp3 expression, whereas the epidermal growth factor receptor tyrosine kinase inhibitor AG1478 blocked the hCG stimulation of both Timp1 and Timp3 expression. The prostaglandin-endoperoxide synthase 2 inhibitor NS-398 had no effect. The potential function of TIMP3 was investigated with Timp3-specific small interfering RNA treatment. Timp3 small interfering RNA resulted in a 20% decrease in hCG-induced progesterone levels and microarray analysis revealed an increase in cytochrome P450 Cyp 17, ubiquitin conjugating enzyme E2T, and heat shock protein 70. IGF binding protein 5, stearyl-CoA desaturase, and annexin A1 were decreased. The differential regulation between Timp1 and Timp3 may correlate with their unique roles in the processes of ovulation and luteinization. For TIMP3, this may include regulating fatty acid synthesis, steroidogenesis, and protein turnover.
Attenuation of Induced Hyperthyroidism in Mice by Pretreatment with Thyrotropin Receptor Protein: Deviation of Thyroid-Stimulating to Nonfunctional Antibodies
Authors: Misharin Alexander V. , Nagayama Yuji , Aliesky Holly A. , Mizutori Yumiko , Rapoport Basil , McLachlan Sandra M.
Published: April 2009

Graves’-like hyperthyroidism is induced by immunizing BALB/c mice with adenovirus expressing the thyrotropin receptor (TSHR) or its A-subunit. Nonantigen-specific immune strategies can block disease development and some reduce established hyperthyroidism, but these approaches may have unforeseen side effects. Without immune stimulation, antigens targeted to the mannose receptor induce tolerance. TSHR A-subunit protein generated in eukaryotic cells binds to the mannose receptor. We tested the hypothesis that eukaryotic A-subunit injected into BALB/c mice without immune stimulation would generate tolerance and protect against hyperthyroidism induced by subsequent immunization with A-subunit adenovirus. Indeed, one sc injection of eukaryotic, glycosylated A-subunit protein 1 wk before im A-subunit-adenovirus immunization reduced serum T4 levels and the proportion of thyrotoxic mice decreased from 77 to 22%. Prokaryotic A-subunit and other thyroid proteins (thyroglobulin and thyroid peroxidase) were ineffective. A-subunit pretreatment reduced thyroid-stimulating and TSH-binding inhibiting antibodies, but, surprisingly, TSHR-ELISA antibodies were increased. Rather than inducing tolerance, A-subunit pretreatment likely expanded B cells that secrete nonfunctional antibodies. Follow-up studies supported this possibility and also showed that eukaryotic A-subunit administration could not reverse hyperthyroidism in mice with established disease. In conclusion, glycosylated TSHR A-subunit is a valuable immune modulator when used before immunization. It acts by deviating responses away from pathogenic toward nonfunctional antibodies, thereby attenuating induction of hyperthyroidism. However, this protein treatment does not reverse established hyperthyroidism. Our findings suggest that prophylactic TSHR A-subunit protein administration in genetically susceptible individuals may deviate the autoantibody response away from pathogenic epitopes and provide protection against future development of Graves’ disease.
Minireview: Finding the Sweet Spot: Peripheral Versus Central Glucagon-Like Peptide 1 Action in Feeding and Glucose Homeostasis
Authors: Williams Diana L.
Published: April 2009

Glucagon-like peptide 1 (GLP-1) is both a gut-derived hormone and a neurotransmitter synthesized in the brain. Early reports suggested that GLP-1 acts in the periphery to promote insulin secretion and affect glucose homeostasis, whereas central GLP-1 reduces food intake and body weight. However, current research indicates that in fact, GLP-1 in each location plays a role in these functions. This review summarizes the evidence for involvement of peripheral and brain GLP-1 in food intake regulation and glucose homeostasis and proposes a model for the coordinated actions of GLP-1 at multiple sites.
Mutations in zebrafish leucine-rich repeat-containing six-like affect cilia motility and result in pronephric cysts, but have variable effects on left-right patterning
Authors: Serluca Fabrizio C. , Xu Bo , Okabe Noriko , Baker Kari , Lin Shin-Yi , Sullivan-Brown Jessica , Konieczkowski David J. , Jaffe Kimberly M. , Bradner Joshua M. , Fishman Mark C. , Burdine Rebecca D.
Published: April 2009

Cilia defects have been implicated in a variety of human diseases and genetic disorders, but how cilia motility contributes to these phenotypes is still unknown. To further our understanding of how cilia function in development, we have cloned and characterized two alleles of seahorse, a zebrafish mutation that results in pronephric cysts. seahorse encodes Lrrc6l, a leucine-rich repeat-containing protein that is highly conserved in organisms that have motile cilia. seahorse is expressed in zebrafish tissues known to contain motile cilia. Although mutants do not affect cilia structure and retain the ability to interact with Disheveled, both alleles of seahorse strongly affect cilia motility in the zebrafish pronephros and neural tube. Intriguingly,although seahorse mutations variably affect fluid flow in Kupffer's vesicle, they can have very weak effects on left-right patterning. Combined with recently published results, our alleles suggest that the function of seahorse in cilia motility is separable from its function in other cilia-related phenotypes.
Insights into neural crest migration and differentiation from experimental embryology
Authors: Kuratani Shigeru
Published: April 2009

In this essay, I discuss two studies published in the Journal of Experimental Embryology and Morphology that represent how experimental embryologists began to deal with the issue of the vertebrate body plan. In one such study by Nicole Le Douarin and Marie-Aimée Teillet, the neural crest was unequivocally identified as being the origin of the chick enteric nervous system through careful chimeric experiments and histological analyses. In the second, Michael Rickmann and colleagues showed how to combine immunohistochemical and experimental techniques in a study of the segmental patterning of the spinal nerves of the chick embryo.
Metastable Processes Investigated on an Orthogonal-Axis Time-of-Flight Instrument: Mass-Scale Calibration and Application
Authors: De Winter Julien , Goffin Anne-Lise , Coulembier Olivier , Dubois Philippe , Flammang Robert , Gerbaux Pascal
Published: April 2009

In this letter, the authors would like to present a rapid method for mass-scale calibration of metastable dissociation in an orthogonal-axis time-of-flight instrument. The calibrating ion is a protonated polyhedral oligomeric silsesquioxane (POSS) generated in electrospray ionization. In addition, dissociation mechanisms for protonated POSS are proposed. Finally, the interest of the method is illustrated in the context of a collision-induced dissociation investigation of a sodium-cationized polylactide.
Solvation in Gas-Phase Reactions of Sulfonic Groups Containing Ionic Liquids in Electrospray Ionization Quadrupole Ion Trap Mass Spectrometry
Authors: Cao Xiaoji , Yu Yi , Ye Xueming , Mo Weiming
Published: April 2009

In electrospray ionization (ESI) quadrupole ion trap mass spectrometry, certain fragment ions generated in the ion trap from a series of sulfonic groups containing ionic liquids (ILs) are found to undergo ion–molecule reactions with ESI solvent molecules (water, acetonitrile and methanol) to form adduct species. These unexpected solvated fragment ions severely complicate the interpretation of mass spectrometric data. Multi-stage fragmentation mass spectra were used to ascertain the chemical structures of these adduct species. It is important that solvation must be taken into account in order to prevent erroneous data interpretation for sulfonic groups containing ILs.
Decomposition of Charge-State Distributions for Better Understanding of Electrospray Mass Spectra of Bioorganic Compounds. Part 2: Application of the Method
Authors: Raznikov Valeriy V. , Raznikova Marina O.
Published: April 2009

The results of the analysis of electrospray mass spectra of β-endorphin and chicken egg lysozyme in different conditions of data acquisition using the method described in Part 1 of the work are reported. At least partial unfolding during the process of ion formation in the electrospray ion source of an initially native biomolecule of lyzozyme in solution should supposedly explain the received set of probabilities of proton retention by basic and acidic residues of this molecule for all considered conditions of data acquisition.
An extra double-stranded RNA binding domain confers high activity to a squid RNA editing enzyme
Authors: Palavicini Juan Pablo , O'connell Mary A. , Rosenthal Joshua J.C.
Published: April 2009

RNA editing by adenosine deamination is particularly prevalent in the squid nervous system. We hypothesized that the squid editing enzyme might contain structural differences that help explain this phenomenon. As a first step, a squid adenosine deaminase that acts on RNA (sqADAR2a) cDNA and the gene that encodes it were cloned from the giant axon system. PCR and RNase protection assays showed that a splice variant of this clone (sqADAR2b) was also expressed in this tissue. Both versions are homologous to the vertebrate ADAR2 family. sqADAR2b encodes a conventional ADAR2 family member with an evolutionarily conserved deaminase domain and two double-stranded RNA binding domains (dsRBD). sqADAR2a differs from sqADAR2b by containing an optional exon that encodes an “extra” dsRBD. Both splice variants are expressed at comparable levels and are extensively edited, each in a unique pattern. Recombinant sqADAR2a and sqADAR2b, produced in Pichia pastoris, are both active on duplex RNA. Using a standard 48-h protein induction, both sqADAR2a and sqADAR2b exhibit promiscuous self-editing; however, this activity is particularly robust for sqADAR2a. By decreasing the induction time to 16 h, self-editing was mostly eliminated. We next tested the ability of sqADAR2a and sqADAR2b to edit two K+ channel mRNAs in vitro. Both substrates are known to be edited in squid. For each mRNA, sqADAR2a edited many more sites than sqADAR2b. These data suggest that the “extra” dsRBD confers high activity on sqADAR2a.
Gene regulation by sense–antisense overlap of polyadenylation signals
Authors: Gu Rui , Zhang Zuo , DeCerbo Joshua N. , Carmichael Gordon G.
Published: April 2009

We show here that expression of genes from convergent transcription units can be regulated by the formation of double-stranded RNA (dsRNA) in the region of overlapping polyadenylation signals. The model system employed is the mouse polyomavirus. The early and late genes of polyomavirus are transcribed from opposite strands of the circular viral genome. At early times after infection, the early genes are expressed predominantly. Late gene expression increases dramatically upon the onset of DNA replication, when a major defect in polyadenylation of the late primary transcripts generates multigenomic RNAs that are precursors to the mature late mRNAs. Embedded in these late pre-mRNAs are sequences complementary to the early RNAs that act to down-regulate early gene expression via A-to-I editing of dsRNAs. In this system, the defective polyadenylation, and consequently the production of multigenomic late RNAs, depends on the context, and perhaps also, on the A-to-I editing of the poly(A) signal that overlaps the 3′-end of early transcripts.
Electronic and Physical Market Channels: A Multiyear Investigation in a Market for Products of Uncertain Quality
Authors: Overby Eric , Jap Sandy
Published: April 2009

Many markets that have traditionally relied on collocation of buyers, sellers, and products have introduced electronic channels. Although these electronic channels may provide benefits to buyers and sellers by lowering the transaction costs of participating in the market, there are trade-offs related to quality uncertainty and increased risk that may limit the adoption of the electronic channels. As a result, buyers and sellers use physical channels for some transactions and electronic channels for others. These usage patterns may evolve over time, particularly when the electronic channels are new. We examine buyer and seller use of electronic and physical channels in a market for products of uncertain quality (used vehicles) over a 2.5-year period. Results indicate that transactions involving low quality uncertainty and relatively rare products occurred in the electronic channels, whereas transactions involving high quality uncertainty and relatively plentiful products occurred in the physical channels. These patterns became clearer over time as buyers and sellers gained experience with the electronic channels. The electronic channels led to discounts for products of high quality uncertainty, but not for those of low quality uncertainty.
Hindsight Bias, Risk Perception, and Investment Performance
Authors: Biais Bruno , Weber Martin
Published: April 2009

Once they have observed information, hindsight-biased agents fail to remember how ignorant they were initially; “they knew it all along.” We formulate a theoretical model of this bias, providing a foundation for empirical measures and implying that hindsight-biased agents learning about volatility will underestimate it. In an experiment involving 66 students from Mannheim University, we find that hindsight bias reduces volatility estimates. In another experiment, involving 85 investment bankers in London and Frankfurt, we find that more biased agents have lower performance. These findings are robust to differences in location, information, overconfidence, and experience.
Use of Virtual Reality Tasks to Assess Prospective Memory: Applicability and Evidence
Authors: Knight Robert G. , Titov Nickolai
Published: April 2009

Virtual reality (VR) is a term used to describe computer-generated virtual environments that the patient can explore and interact with in real time. In this review, the use of VR to construct ecologically valid tasks for use in neuropsychological assessment and rehabilitation is discussed with particular reference to the measurement of prospective memory (PM) abilities. PM, the ability to act upon delayed intentions, is an example of an everyday ability requiring the coordination of a different cognitive processes that is ideally suited to research and rehabilitation using VR. Studies investigating PM and related abilities in patients with brain impairments are surveyed, and it is established that there is evidence for the utility of applying VR procedures to measure prospective remembering. Future research could usefully focus on the construction of a standardised testing procedure with credible psychometric characteristics. In particular, there needs to be evidence for the criterion validity of such tests. Another potential research avenue is the evaluation of VR platforms as tools to teach memory skills and awareness of impairments. It is concluded that difficulties in adapting programs to specific clinical needs, technical issues, and the reluctance of many clinicians to use computer-based technology need to be overcome before VR is likely to be widely used to measure PM.
Validity of the Comprehensive Assessment of Prospective Memory (CAPM) for Use With Adults With Traumatic Brain Injury
Authors: Fleming Jennifer , Kennedy Sahra , Fisher Rebecca , Gill Hannah , Gullo Matthew , Shum David
Published: April 2009

Objective: To expand upon the existing psychometric properties of the Comprehensive Assessment of Prospective Memory (CAPM) for use with adults with traumatic brain injury by examining concurrent and criterion validity. Method: Participants were 45 adults with a traumatic brain injury. Participants and their relatives completed Section A of the CAPM and a measure of psychosocial integration. Participants were also administered two neuropsychological tests of prospective memory, the Cambridge Prospective Memory Test (CAM-PROMPT) and the Memory Intentions Screening Test (MIST). Concurrent validity was measured by comparing scores on the CAPM with scores on the CAM-PROMPT and MIST. Criterion validity was examined by correlating CAPM scores with level of psychosocial integration. Results: Participant self-reports on the CAPM were not significantly correlated with the CAM-PROMPT or MIST, but were significantly correlated with level of psychosocial integration. Relative reports on the CAPM were correlated significantly with total score on the MIST and CAM-PROMPT and level of psychological integration. Conclusions: The findings indicate that the concurrent validity of the self-report version of CAPM is low suggesting that self-reports alone do not provide an objective measure for assessing prospective memory function. The relative report version however, demonstrated reasonable concurrent and criterion validity, suggesting that the relative report version of the Section A of the CAPM is a useful means of evaluating frequency of prospective memory failure in adults with traumatic brain injury.
Traumatic Brain Injury and Prospective Memory in a Virtual Shopping Trip Task: Does It Matter Who Generates the Prospective Memory Target?
Authors: Kinsella Glynda J. , Ong Ben , Tucker Jodie
Published: April 2009

The current study aimed to investigate prospective memory in traumatic brain injury by using a laboratory-based but naturalistic style assessment task. The objective was to determine if performance differed when the prospective memory targets were self-generated or experimenter-generated (a generation effect). Sixteen people who had sustained a traumatic brain injury and had received rehabilitation were compared to 16 healthy age-matched control participants on a naturalistic virtual measure of shopping and prospective memory. Results demonstrated that the traumatic brain group was less accurate in overall prospective remembering performance than the control group but there was a lack of difference between the self- and experimenter-generated prospective memory targets for both participant groups. Both retrospective memory and executive attention of working memory were associated with prospective memory performance in the naturalistic task. The findings of the study suggest that the generation effect commonly observed in retrospective memory performance may not impact performance in prospective memory.
Prospective Memory Intervention: A Review and Evaluation of a Pilot Restorative Intervention
Authors: Raskin Sarah A. , Sohlberg McKay Moore
Published: April 2009

Prospective memory impairments continue to be among the greatest impediments to return to work for individuals following neurological illness or injury. Current approaches to prospective memory intervention are reviewed in this article. These include behavioral interventions, metacognitive strategies and restorative approaches. In addition, the summary of a study using the restorative approach is presented and discussed. Eight subjects were given a course of prospective memory training designed to increase the length of time that they are able to maintain to-be-performed tasks in mind. These subjects demonstrated improvement on neurospsychological measures, a standardised measure of prospective memory and a generalisation measure of prospective memory in daily life. These data lend support to the notion that prospective memory may be one area of cognition that is responsive to restorative intervention approaches.
Schoenberg's Symbolic Remigration: A Survivor from Warsaw in Postwar West Germany
Authors: Calico Joy H.
Published: April 2009

Musicologists have recently begun to study a crucial component in the reconstruction of European cultural life after World War II—the remigration of displaced musicians, either in person or (adopting Marita Krauss's notion of "remigrating ideas") in the form of their music. Because composers are most significantly present in the aural materiality of their music, and because Arnold Schoenberg's name was synonymous with modernism and its persecution across Europe, his symbolic postwar reappearance via performances of his music was a powerful and problematic form of remigration.

The case of Schoenberg's A Survivor from Warsaw and the former Nazi music critic Hans Schnoor serves as a representative example. Schnoor derided Schoenberg and Survivor in a newspaper column in 1956 using the rhetoric of National Socialist journalism as part of his campaign against federal funding of musical modernism via radio and festivals. When radio journalist Fred Prieberg took him to task for this on the air, Schnoor sued for defamation. A series of lawsuits ensued in which issues of denazification and the occupying Allied forces put a distinctly West German spin on the universal postwar European themes of anti-Semitism, the Holocaust, remigration, and modernism.
Serological screening for coeliac disease in adults with Turner's syndrome: prevalence and clinical significance of endomysium antibody positivity
Authors: Frost Amy R , Band Margaret M , Conway Gerard S
Published: April 2009

Objective

To investigate the prevalence of coeliac disease (CD) in an adult population with Turner's syndrome (TS).

Design

A clinic population with TS was screened using a serological test for CD.

Methods

Two hundred and fifty six patients with TS were included in the study. Five patients had existing diagnoses of CD. The remaining 251 asymptomatic patients were screened using an IgA endomysium antibody (EMA) test. Positive cases were offered endoscopy with duodenal biopsy. HLA typing was undertaken in existing cases and new EMA-positive cases.

Results

Of the 251 patients screened, eight were found to be EMA positive (3.2%). Seven patients proceeded to duodenal biopsy on which all were confirmed histologically to have CD (2.8%). The prevalence of subclinical CD in the population can therefore be estimated between 2.8 and 3.2%. The total population prevalence of CD, including the previously diagnosed cases, is estimated between 4.7 and 5.1%. Ten patients with histologically confirmed CD underwent HLA typing of which eight were HLA-DQ2 positive, one was HLA-DQ8 positive and one was negative to both HLA-DQ2 and HLA-DQ8.

Conclusions

This study demonstrates an increased prevalence of CD in an adult population with TS over the general population. This is consistent with previous data published in paediatric populations.
Development and refinement of a portable electronic device for haematocrit determination
Authors: Groenewald A.J. , Pieters H.
Published: April 2009

A small portable eletronic device, named a blood electrometer (BEM), was developed to measure packed cell volume, which can be related to haematocrit (Hct). The electronic circuitry is simple and constructed from standard components. Being battery powered, the device is suitable for bedside or field use ('point-of-care-testing') without specialized training. The effects of temperature, anticoagulants, lipid content, electrode type and different BEM electronic circuits on measurement accuracy were evaluated. A method for calibrating the instrument with a sodium chloride calibrator was also devised and evaluated for measurement accuracy. The response of the BEM to Hct is non-linear; a binomial regression function was used to fit the non-linear response to provide accurate Hct values from BEM readings over a wide range of measurements. The BEM response curve is sensitive to the anticoagulant type used, but specific binomial functions reduce error to between –3.1% and +3.3% Hct units. Lipids do not significantly affect BEM readings, even at high concentrations of 9.8 mmol/l. We conclude that the BEM can be relied on for acceptably accurate Hct measurements under a variety of conditions, and can be used for the indirect determination of packed cell volume.
Ocean currents south of Africa from drifters
Authors: Durgadoo J.V. , Ansorge I.J. , Lutjeharms J.R.E.
Published: April 2009

The ocean currents and their variability south of Africa are known to cover a wide spectrum, spatially and possibly temporally. Hydrographic observations in this vast ocean region are logistically demanding and expensive. In recent years the prevalence of drifting buoys has allowed one to infer certain current characteristics for the region that otherwise would be difficult. Observations from satellite-tracked drifters drogued at a depth of 15 m, collected between 1988 and 2005, were used to infer the mean surface circulation and kinetic energy distributions of the surface flow in the African sector of the Southern Ocean between 30 and 60°S. Regions of intensified flow and of higher levels of eddy kinetic energy were identified and agree fairly well with those established from remote sensing products. These results confirm the value of these observations and indicate the increasing usefulness of this data set as the number of drifter tracks increases.