bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammasome-independent role of the apoptosis-associated speck-like protein containing CARD (ASC) in the adjuvant effect of MF59
Authors: Ellebedy Ali H. , Lupfer Christopher , Ghoneim Hazem E. , DeBeauchamp Jennifer , Kanneganti Thirumala-Devi , Webby Richard J.
Published: January 2011

Clinical studies have indicated that subvirion inactivated vaccines against avian influenza viruses, particularly H5N1, are poorly immunogenic in humans. As a consequence, the use of adjuvants has been championed for the efficient vaccination of a naïve population against avian influenza. Aluminum salts (alum) and the oil-in-water emulsion MF59 are safe and effective adjuvants that are being used with influenza vaccines, but the mechanism underlying their stimulation of the immune system remains poorly understood. It was shown recently that activation of a cytosolic innate immune-sensing complex known as “NLR-Pyrin domain containing 3” (NLRP3) inflammasome, also known as “cryopyrin,” “cold-induced autoinflammatory syndrome 1” (CIAS1), or nacht domain-, leucine-rich repeat-, and PYD-containing protein 3 (Nalp3), is essential for the adjuvant effect of alum. Here we show that the inflammasome component apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), an adapter protein within the NLRP3 inflammasome, is a crucial element in the adjuvant effect of MF59 when combined with H5N1 subunit vaccines. In the absence of ASC, H5-specific IgG antibody responses are significantly reduced, whereas the responses are intact in NLRP3
−/−
and caspase-1
−/−
mice. This defect is caused mainly by the failure of antigen-specific B cells to switch from IgM to IgG production. We conclude that ASC plays an inflammasome-independent role in the induction of antigen-specific humoral immunity after vaccination with MF59-adjuvanted influenza vaccines. These findings have important implications for the rational design of next-generation adjuvants.
Protein-only mechanism induces self-perpetuating changes in the activity of neuronal
Aplysia
cytoplasmic polyadenylation element binding protein (CPEB)
Authors: Heinrich Sven U. , Lindquist Susan
Published: January 2011

Neuronal cytoplasmic polyadenylation element binding protein (CPEB) plays a critical role in maintaining the functional and morphological long-lasting synaptic changes that underlie learning and memory. It can undergo a prion switch, but it remains unclear if this self-templating change in protein conformation is alone sufficient to create a stable change in CPEB activity: a robust “protein-only” biochemical memory. To investigate, we take advantage of yeast cells wherein the neuronal CPEB of
Aplysia
is expressed in the absence of any neuronal factors and can stably adopt either an active or an inactive state. Reminiscent of well-characterized yeast prions, we find that CPEB can adopt several distinct activity states or “strains.” These states are acquired at a much higher spontaneous rate than is typical of yeast prions, but they are extremely stable—perpetuating for years—and have all of the non-Mendelian genetic characteristics of bona fide yeast prions. CPEB levels are too low to allow direct physical characterization, but CPEB strains convert a fusion protein, which shares only the prion-like domain of CPEB, into amyloid in a strain-specific manner. Lysates of CPEB strains seed the purified prion domain to adopt the amyloid conformation with strain-specific efficiencies. Amyloid conformers generated by spontaneous assembly of the purified prion domain (and a more biochemically tractable derivative) transformed cells with inactive CPEB into the full range of distinct CPEB strains. Thus, CPEB employs a prion mechanism to create stable, finely tuned self-perpetuating biochemical memories. These biochemical memories might be used in the local homeostatic maintenance of long-term learning-related changes in synaptic morphology and function.
Coupling characteristics of the ITER-relevant lower hybrid antenna in Tore Supra: experiments and modelling
Authors: Preynas M. , Ekedahl A. , Fedorczak N. , Goniche M. , Guilhem D. , Gunn J.P. , Hillairet J. , Litaudon X. , Achard J. , Berger-By G. , Belo J. , Corbel E. , Delpech L. , Ohsako T. , Prou M.
Published: January 2011

A new concept of lower hybrid antenna for current drive has been proposed for ITER (Bibet et al
1995 Nucl. Fusion
35 1213–23): the passive active multijunction (PAM) antenna that relies on a periodic combination of active and passive waveguides. An actively cooled PAM antenna at 3.7 GHz has recently been installed on the tokamak Tore Supra. This paper summarizes the comprehensive experimental characterization of the coupling properties of the PAM antenna to the Tore Supra plasmas. In this paper, the electromagnetic properties of the antenna are measured at a reduced power (<1 MW) to allow a systematic comparison with linear wave coupling theory and the associated modelling based on the linear ALOHA code. In a wide range of edge electron densities at the antenna aperture (spanning a factor 20 from 0.5 × n
c to 10 × n
c where n
c is the slow wave density cut-off, n
c = 1.7 × 1017 m−3 at 3.7 GHz) and antenna phasing, the ALOHA simulations reproduce the experimental results observed on Tore Supra. In addition, reduced power reflection coefficients (<5%) are measured at a low edge density, close to n
c, i.e. in the range 0.5–3 × n
c. Measurement and analysis with ALOHA of the antenna–plasma scattering matrices provide explanation of the good coupling properties of the PAM antenna close to n
c by highlighting the crucial role of the slow wave intercoupling between active and passive waveguides through the plasma edge. This detailed validation of the coupling modelling is an important step towards the validation of the PAM concept in view of further optimizing the electromagnetic properties of the future ITER antenna.
Soluble levels of cytosolic tubulin regulate ciliary length control
Authors: Sharma Neeraj , Kosan Zachary A. , Stallworth Jannese E. , Berbari Nicolas F. , Yoder Bradley K.
Published: January 2011

The primary cilium is an evolutionarily conserved dynamic organelle important for regulating numerous signaling pathways, and, as such, mutations disrupting ciliogenesis result in a variety of developmental abnormalities and postnatal disorders. The length of the cilium is regulated by the cell through largely unknown mechanisms. Normal cilia length is important, as either shortened or elongated cilia have been associated with disease and developmental defects. Here we explore the importance of cytoskeletal dynamics in regulating cilia length. Using pharmacological approaches in different cell types, we demonstrate that actin depolymerization or stabilization and protein kinase A activation result in a rapid elongation of the primary cilium. The effects of pharmacological agents on cilia length are associated with a subsequent increase in soluble tubulin levels and can be impaired by depletion of soluble tubulin with taxol. In addition, subtle nocodazole treatment was able to induce ciliogenesis under conditions in which cilia are not normally formed and also increases cilia length on cells that have already established cilia. Together these data indicate that cilia length can be regulated through changes in either the actin or microtubule network and implicate a possible role for soluble tubulin levels in cilia length control.
The NDC80 complex proteins Nuf2 and Hec1 make distinct contributions to kinetochore–microtubule attachment in mitosis
Authors: Sundin Lynsie J.R. , Guimaraes Geoffrey J. , DeLuca Jennifer G.
Published: January 2011

Successful mitosis requires that kinetochores stably attach to the plus ends of spindle microtubules. Central to generating these attachments is the NDC80 complex, made of the four proteins Spc24, Spc25, Nuf2, and Hec1/Ndc80. Structural studies have revealed that portions of both Hec1 and Nuf2 N termini fold into calponin homology (CH) domains, which are known to mediate microtubule binding in certain proteins. Hec1 also contains a basic, positively charged stretch of amino acids that precedes its CH domain, referred to as the “tail.” Here, using a gene silence and rescue approach in HeLa cells, we show that the CH domain of Hec1, the CH domain of Nuf2, and the Hec1 tail each contributes to kinetochore–microtubule attachment in distinct ways. The most severe defects in kinetochore–microtubule attachment were observed in cells rescued with a Hec1 CH domain mutant, followed by those rescued with a Hec1 tail domain mutant. Cells rescued with Nuf2 CH domain mutants, however, generated stable kinetochore–microtubule attachments but failed to generate wild-type interkinetochore tension and failed to enter anaphase in a timely manner. These data suggest that the CH and tail domains of Hec1 generate essential contacts between kinetochores and microtubules in cells, whereas the Nuf2 CH domain does not.
Interpopulation variation in a fish predator drives evolutionary divergence in prey in lakes
Authors: Walsh Matthew R. , Post David M.
Published: January 2011

Ecological factors are known to cause evolutionary diversification. Recent work has shown that evolution in strongly interacting predator species has reciprocal impacts on ecosystems. These divergent impacts of predators may alter the selective landscape and cause the evolution of prey. Yet, this link between intraspecific variation and evolution is unexplored. We compared the life history of a species of zooplankton (
Daphnia ambigua
) from lakes in New England in which the dominant planktivorous predator, the alewife (
Alosa pseudoharengus
), differs in feeding traits and migratory behaviour. Anadromous alewife (seasonal migrants) exhibit larger gapes, gill-raker spacing and target larger prey than landlocked alewife (year-round freshwater resident). In ‘anadromous’ lakes,
Daphnia
are abundant in the spring but extirpated by alewife predation in summer.
Daphnia
are rare year-round in ‘landlocked’ lakes. We show that
Daphnia
from lakes with anadromous alewife grew faster, matured earlier but at the same size and produced more offspring than
Daphnia
from lakes with landlocked or no alewife across multiple temperature and resource treatments. Our results are inconsistent with a response to size-selective predation but are better explained as an adaptation to colder temperatures and shorter periods of development (countergradient variation) mediated by seasonal alewife predation.
Re-evaluation of the genome sequence of guinea pig cytomegalovirus
Authors: Kanai Kyosuke , Yamada Souichi , Yamamoto Yumiko , Fukui Yoshiko , Kurane Ichiro , Inoue Naoki
Published: January 2011

Congenital infection by human cytomegalovirus (HCMV) is a major cause of birth defects and developmental abnormalities. Since guinea pig cytomegalovirus (GPCMV) crosses the placenta and causes infection in utero, GPCMV models are useful for studies of the mechanisms of transplacental transmission. During our characterization of a genomic locus required for GPCMV dissemination in animals, we found that the nucleotide sequence in and around the nearby immediate–early genes in our lineage of GPCMV strain 22122 [designated GPCMV (ATCC-P5)] showed clear differences from that reported previously for the same strain [designated GPCMV (UMN)] passaged extensively in vitro. Since in vitro passaging of HCMV is known to result in genetic alterations, especially in the UL128–UL131A locus, and loss of growth ability in particular cell types, in this study we determined the complete genome sequence of GPCMV (ATCC-P5), which grows efficiently in animals. A total of 359 differences were identified between the genome sequences of GPCMV (UMN) and GPCMV (ATCC-P5), and these resulted in structural differences in 29 protein-encoding regions. In addition, some genes predicted from our analysis but not from GPCMV (UMN) are well conserved among cytomegaloviruses. An additional 18 passages of GPCMV (ATCC-P5) in vitro generated no further marked alterations in these genes or in the locus corresponding to the HCMV UL128–UL131A. Our analyses indicate that the published sequence of GPCMV (UMN) contains a substantial number of sequencing errors and, possibly, some mutations resulting from a long history of passaging in vitro. Our re-evaluation of the genetic content of GPCMV will provide a solid foundation for future studies.
Capsid proteins from field strains of foot-and-mouth disease virus confer a pathogenic phenotype in cattle on an attenuated, cell-culture-adapted virus
Authors: Bøtner Anette , Kakker Naresh K. , Barbezange Cyril , Berryman Stephen , Jackson Terry , Belsham Graham J.
Published: January 2011

Chimeric foot-and-mouth disease viruses (FMDVs) have been generated from plasmids containing full-length FMDV cDNAs and characterized. The parental virus cDNA was derived from the cell-culture-adapted O1Kaufbeuren B64 (O1K B64) strain. Chimeric viruses, containing capsid coding sequences derived from the O/UKG/34/2001 or A/Turkey 2/2006 field viruses, were constructed using the backbone from the O1K B64 cDNA, and viable viruses (O1K/O-UKG and O1K/A-Tur, respectively) were successfully rescued in each case. These viruses grew well in primary bovine thyroid cells but grew less efficiently in BHK cells than the rescued parental O1K B64 virus. The two chimeric viruses displayed the expected antigenicity in serotype-specific antigen ELISAs. Following inoculation of each virus into cattle, the rescued O1K B64 strain proved to be attenuated whereas, with each chimeric virus, typical clinical signs of foot-and-mouth disease were observed, which then spread to in-contact animals. Thus, the surface-exposed capsid proteins of the O1K B64 strain are responsible for its attenuation in cattle. Consequently, there is no evidence for any adaptation, acquired during cell culture, outside the capsid coding region within the O1K B64 strain that inhibits replication in cattle. These chimeric infectious cDNA plasmids provide a basis for the analysis of FMDV pathogenicity and characterization of receptor utilization in vivo.
Carboxyl terminus of Hsp70‐interacting protein (CHIP) contributes to human glioma oncogenesis
Authors: Xu Tao , Zhou Quan , Zhou Jingxu , Huang Yan , Yan Yong , Li Weiqing , Wang Chunlin , Hu Guohan , Lu Yicheng , Chen Juxiang
Published: January 2011

Malignant glioma is the most common adult primary brain tumor, and the mechanism of its oncogenesis is poorly understood. Growing evidence has shown that E3 ubiquitin ligases can promote tumorgenesis of glioma. CHIP is an E3 ubiquitin ligase that can induce ubiquitylation and degradation of many tumor‐related proteins, and it has been reported to act as an upstream regulator in breast cancer; however, its role in human gliomas has not been evaluated yet. In this study, the expression of CHIP in glioma tissues was studied using immunohistochemistry. CHIP expression in glioma cells was studied by real‐time RT‐PCR, western blot and double immunofluorescence staining. The role of CHIP in glioma oncogenesis was investigated by lentivirus‐mediated RNA interference (RNAi) and overexpression in vitro and in vivo. We showed CHIP expression in glioma samples was related to tumor grades, with stronger staining in high‐grade gliomas than in low‐grade gliomas. Knocking down of CHIP suppressed proliferation, colony formation of U251 and U87 glioma cells, while overexpression of CHIP resulted in enhanced proliferation and colony formation in vitro. In a nude mouse xenograft model, intratumoral injection of CHIP RNAi lentivirus significantly delayed tumor growth. In contrast, overexpression of CHIP resulted in enhanced tumor growth in vivo. After CHIP RNAi, both survivin mRNA and protein were decreased, while CHIP overexpression induced increased mRNA and protein levels of survivin. This is the first study demonstrating CHIP contributes to oncogenesis of glioma. (Cancer Sci 2011; 102: 959–966)
Modelling of pain intensity and informative dropout in a dental pain model after naproxcinod, naproxen and placebo administration
Authors: Björnsson Marcus A. , Simonsson Ulrika S. H.
Published: January 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Modelling has been used to describe the pain relief and dropout for a few non‐steroidal anti‐inflammatory drugs.

WHAT THIS STUDY ADDS

• This study shows the relationship between dose, plasma concentration, pain intensity and dropout for naproxen and naproxcinod. It also extends previous models by using a visual analogue scale for pain intensity instead of modelling pain relief on a categorical scale, and shows the value of including informative dropout in the simulations for visual predictive checks.

AIMS To describe pain intensity (PI) measured on a visual analogue scale (VAS) and dropout due to request for rescue medication after administration of naproxcinod, naproxen or placebo in 242 patients after wisdom tooth removal.

METHODS Non‐linear mixed effects modelling was used to describe the plasma concentrations of naproxen, either formed from naproxcinod or from naproxen itself, and their relationship to PI and dropout. Goodness of fit was assessed by simultaneous simulations of PI and dropout.

RESULTS Baseline PI for the typical patient was 52.7 mm. The PI was influenced by placebo effects, using an exponential model, and by naproxen concentrations using a sigmoid Emax model. Typical maximal placebo effect was a decrease in PI by 20.2%, with an onset rate constant of 0.237 h−1. EC50 was 0.135 µmol l−1. A Weibull time‐to‐event model was used for the dropout, where the hazard was dependent on the predicted PI and by the PI at baseline. Since the dropout was not at random, it was necessary to include the simulated dropout in visual predictive checks (VPC) of PI.

CONCLUSIONS This model describes the relationship between drug effects, PI and the likelihood of dropout after naproxcinod, naproxen and placebo administration. The model provides an opportunity to describe the effects of other doses or formulations, after dental extraction. VPC created by simultaneous simulations of PI and dropout provides a good way of assessing the goodness of fit when there is informative dropout.
Understanding the time course of pharmacological effect: a PKPD approach
Authors: Wright Daniel F. B. , Winter Helen R. , Duffull Stephen B.
Published: January 2011

The key concepts that underpin the choice of drug and dosing regimen are an understanding of the drugs' effectiveness, the potential for adverse effects, and the expected time course over which both desired and adverse effects are likely to occur. Research in clinical pharmacology should therefore address three fundamental questions: (1) What is the magnitude of drug effects (beneficial or adverse) from a given dose? (2) How quickly will any given effects occur? (3) How long will these effects last? Under steady‐state conditions, only the magnitude of drug effects can be examined. This requires researchers to consider non‐steady‐state conditions, which require more complex models and an understanding of the mechanisms that drive the time course of drug effect. The aim of this review is to provide a conceptual framework for understanding the time course of drug effects using pharmacokinetic–pharmacodynamic models. Key examples will illustrate how this can inform the optimal use of drugs in the clinic.
Person‐centred medicine in the context of primary care: a view from the World Organization of Family Doctors (Wonca)
Authors: van Weel Chris
Published: January 2011

Rationale, aims and objectives  Most professional medical care is provided in the community, and this determines the importance of primary care for the health care system. As family doctors are involved in the care of different health problems over time to the same individual, the personal dimension is strong. This paper analyses the importance of person‐centred medicine from the perspective of primary care and family medicine.

Methods  The views and opinions of the leadership of the World Organization of Family Doctors, Wonca, provided the background material. Wonca brings together national colleges and academies of family medicine around the world.

Results  The community, with its social, cultural and economic characteristics, is an important determinant of illness, health and disease. This shapes the personal relation between patient and family physician, with its basis of trust, and determines the effectiveness with which primary care functions. Continuity and integration of care are important person‐centred ‘techniques’.

Conclusions  As the effectiveness of primary care is a major factor for overall effective health care, it is important to come to a better understanding of how to address the personal context of care and the mechanisms through which this determines outcome of care.
New Roles for Innate Immune Response in Acute and Chronic Kidney Injuries
Authors: Gonçalves G. M. , Castoldi A. , Braga T. T. , Câmara N. O. S.
Published: January 2011

The innate immune system plays an important role as a first response to tissue injury. This first response is carried out via germline‐encoded receptors. They can recognize exogenous Pathogen‐Associated Molecular Patterns and endogenous Dangers‐Associated Molecular Patterns. The Toll‐Like Receptor (TLR) family is well‐studied, but more recently another family in the cytoplasmic compartment, called nod‐like receptor (NLR), was discovered. In addition to being present in inflammatory cells, these receptors are widely distributed in various cell types, including renal tissue, where these receptors have an important role in triggering the inflammatory response during renal diseases. This review summarizes the present data regarding the role of TLRs and NLRs in the course and development of various kidney pathologies.
The utility of pre‐test clinical scoring for clinical diagnosis of heparin‐induced thrombocytopenia in cardiac surgery patients of a tertiary care centre in North India
Authors: Sachan D. , Gupta N. , Agarwal P. , Chaudhary R.
Published: January 2011

Background: Heparin‐induced thrombocytopenia (HIT) should be diagnosed clinically as well as by laboratory assays for timely recognition, prevention and management of complications.

Objective: To evaluate the clinical utility of pre‐test clinical scoring system in combination with two immunoassays for the diagnosis of HIT in cardiac surgery patients.

Materials and methods: A total of 100 consecutive patients undergoing cardiac surgery were studied. Pre‐test clinical scoring was carried out in patients with thrombocytopenia and further tested by two immunoassays, i.e. Heparin platelet factor 4 (H‐PF4) enzyme‐linked immunosorbent assay (ELISA) and particle gel immunoassay (PaGIA).

Results: Of the 100 patients studied, 42 patients developed thrombocytopenia post‐operatively. On pre‐test clinical scoring, low T‐score was observed in 6 patients, intermediate in 28 and high score in 8 patients, whereas 19 patients (45·2%) were positive by H‐PF4 ELISA and 10 (23·8%) by PaGIA for H‐PF4 antibody. The difference in the incidence of clinically significant HIT antibodies in the three categories was statistically significant. A good correlation was also observed with ELISA optical density, T‐scoring and PaGIA.

Conclusions: Pre‐test clinical scoring correlates well with the development of H‐PF4 antibodies which are incriminated in the causation of thrombotic complications in patients with HIT. We also propose a protocol for diagnosing patients with clinical suspicion of HIT using pre‐test clinical scoring and immunoassay.
WT1‐specific CTL cells of recipient origin may exist in the peripheral blood of patients achieving full donor chimerism soon after nonmyeloablative transplantation
Authors: Wei Li , Zuo Hongli , Sun Xuedong , Liu Tieqiang , Guo Mei , Liu Guangxian , Sun Qiyun , Qiao Jianhui , Wang Danhong , Yu Changlin , Hu Kaixun , Dong Zheng , Ai Huisheng
Published: January 2011

Wei L, Zuo H, Sun X, Liu T, Guo M, Liu G, Sun Q, Qiao J, Wang D, Yu C, Hu K, Dong Z, Ai H. WT1‐specific CTL cells of recipient origin may exist in the peripheral blood of patients achieving full donor chimerism soon after nonmyeloablative transplantation. Clin Transplant 2011: 25: 689–696. © 2011 John Wiley & Sons A/S.

Abstract:  This study was performed to assay whether leukemia‐associated antigen (LAA)‐specific CTLs of recipient origin existed in the blood of patients who achieved full donor chimerism (FDC) soon after nonmyeloablative transplantation (NST). In 15 patients who received haplo‐identical NST, WT1+CD8+CTLs were detected with WT1/HLA‐A*0201 pentamer, and the donor–recipient chimerism levels were analyzed by three methods. Results showed that WT1+CD8+CTLs could be detected in patients with HLA‐A*0201 expressing only in recipient, and cells of recipient origin existed in the blood of patients who achieved FDC, which suggested that LAA‐specific CTLs of recipient origin may exist in patients achieving FDC soon after NST.
Post‐transplant lymphoproliferative disorders: clinicopathological analysis of 43 cases in a single center, 1990–2009
Authors: Yoon Sun Och , Yu Eunsil , Cho Yong Mee , Suh Cheolwon , Kim Kyung Mo , Han Duck Jong , Lee Seung Gyu , Huh Jooryung
Published: January 2011

Yoon SO, Yu E, Cho YM, Suh C, Kim KM, Han DJ, Lee SG, Huh J. Post‐transplant lymphoproliferative disorders: clinicopathological analysis of 43 cases in a single center, 1990–2009.  Clin Transplant 2012: 26: 67–73.  © 2011 John Wiley & Sons A/S.

Abstract:  Post‐transplant lymphoproliferative disorders (PTLDs) are a heterogeneous set of complications of organ transplantation associated with poor patient prognosis. We analyzed the clinicopathological features of PTLDs in 43 adult and pediatric recipients of solid organ or bone marrow transplantation at a large transplant service in the Republic of Korea between 1990 and 2009. Of 4545 solid organ and 747 bone marrow transplant recipients, 37 (0.81%) and 6 (0.8%), respectively, developed heterogeneous types of PTLDs. The cumulative incidences of PTLDs during this period were 1.79% (4/223) for heart transplant recipients, 0.78% (17/2192) for kidney transplant recipients, and 0.77% (16/2067) for liver transplant recipients. The patterns of disease onset, histology, and patient survival were associated with the types of organs transplanted. There is a trend for shorter overall survival (OS) in recipients with early‐onset PTLDs and monomorphic PTLD histology, while kidney transplant recipients showed favorable OS. This study may be the first comprehensive analysis of the characteristics of PTLDs in Korean patients.
Heading date QTL in rice derived from an analysis of chromosome segment substitution lines
Authors: Zhang Y.‐S. , Jiang L. , Liu X. , Liu S. , Chen L. , Zhai H. , Wan J.
Published: January 2011

With 5 figures and 3 tables

The inheritance of heading date (HD) in rice was investigated using a set of lines in which chromosome segments of the photoperiod‐ and temperature‐sensitive male sterile line Peiai 64S had been incorporated into a genetic background of the cv. 9311. The flowering time of each line was contrasted with that of cv. 9311 in four distinct environments: natural long days (13.2–14.2 h photoperiod) and artificially shortened days (9 h photoperiod) at Nanjing; and natural (low) temperature and enhanced temperature at Hainan. A set of 21 heading date quantitative trait loci (QTL) was identified, covering eight of the 12 rice chromosomes, and their dependence on photoperiod and/or temperature was characterized. Two of the QTL were photoperiod‐sensitive, and eight were insensitive; while two were temperature‐sensitive and four insensitive; the remaining five QTL were independent of both temperature and photoperiod. Based on its segregation in an F2 population bred from the cross CSSL C053 ×  cv. 9311, the temperature‐ and photoperiod‐insensitive QTL qHd‐8‐4 was mapped within a segment of chromosome 8 flanked by the SSR marker RM22469 (1.9 cM) and RM72 (2.4 cM).
Automated erythrocytapheresis for severe falciparum malaria
Authors: Harris P. , Price S. , Senthuran S. , Cochupanachimootil J. , Norton R.
Published: January 2011

We describe a case of severe falciparum malaria with hyperparasitaemia. Treatment with automated erythrocytapheresis, in conjunction with parenteral artesunate, produced a rapid and sustained fall in parasite burden. Several poor prognostic features were present at admission. Despite the development of a severe headache with abnormal cerebrospinal fluid parameters and transient pulmonary oedema, a complete recovery was observed. Erythrocytapheresis can be considered in selected cases where facilities exist and has theoretical and practical advantages over traditional methods of red cell exchange transfusion. The paucity of systematic or trial evidence convincingly demonstrating a benefit in terms of morbidity or mortality has limited its application. However, the lack of robust trial data should not in itself invalidate considering this therapeutic option in the appropriate context.
Severe sepsis: take care, take part
Authors: Huggan P. J.
Published: January 2011

Severe sepsis is defined as organ dysfunction in the setting of systemic inflammatory response due to infection. With changes in population age, comorbidity and the delivery of medical care, severe sepsis is increasingly common, and can present in every area of the hospital. The major obstacles to improved outcomes in severe sepsis are deficiencies in healthcare staffing and education, haphazard recognition and response to early clinical deterioration and deviation from optimal management as defined by international guidelines. Major treatment errors were identified in 30% of patients with bacteraemia in one recent investigation. Against this, substantial reductions in mortality can be achieved by improving recognition, urgent care and resuscitation. With a view to improving survival in sepsis, collaborative efforts are required to measure outcomes, implement guidelines and secure adequate funding for ongoing practice improvement, education and research.
Trade‐offs between biomass growth and inducible biosynthesis of polyhydroxybutyrate in transgenic poplar
Authors: Dalton David A. , Ma Cathleen , Shrestha Shreya , Kitin Peter , Strauss Steven H.
Published: January 2011

Polyhydroxybutyrate (PHB) is a bioplastic that can be produced in transgenic plants by the coexpression of three bacterial genes for its biosynthesis. PHB yields from plants have been constrained by the negative impacts on plant health that result from diversion of resources into PHB production; thus, we employed an ecdysone analogue–based system for induced gene expression. We characterized 49 insertion events in hybrid transgenic poplar (Populus tremula x alba) that were produced using Agrobacterium transformation and studied two high‐producing events in detail. Regenerated plants contained up to 1–2% PHB (dry weight) in leaves after 6–8 weeks of induction. Strong induction was observed with 1–10 mm Intrepid and limited direct toxicity observed. Confocal fluorescence microscopy was used to visualize PHB granules in chloroplasts after chemical treatment to reduce autofluorescence. A greenhouse study indicated that there were no negative consequences of PHB production on growth unless the PHB content exceeded 1% of leaf weight; at PHB levels above 1%, growth (height, diameter and total mass) decreased by 10%–34%.
Evaluating post‐Katrina recovery in Mississippi using repeat photography
Authors: Burton Christopher , Mitchell Jerry T. , Cutter Susan L.
Published: January 2011

Hurricane Katrina of August 2005 had extensive consequences for the state of Mississippi in the United States. Widespread infrastructure and property damage, massive social dislocation, and ecological loss remain among the many challenges faced by communities as they work towards ‘normalcy’. This study employs repeat photography to understand differential recovery from Hurricane Katrina in Mississippi. Revealing change with conventional landscape photography, a process known as repeat photography, is common in the natural sciences. Simply stated, repeat photography is the practice of re‐photographing the same scene as it appears in an earlier photograph. Photographs were taken at 131 sites every six months over a three‐year period. Each photograph was assigned a recovery score and a spatially interpolated recovery surface was generated for each time period. The mapped and graphed results show disparities in the progression of recovery: some communities quickly entered the rebuilding process whereas others have lagged far behind.
Repetitive flood victims and acceptance of FEMA mitigation offers: an analysis with community–system policy implications
Authors: Kick Edward L. , Fraser James C. , Fulkerson Gregory M. , McKinney Laura A. , De Vries Daniel H.
Published: January 2011

Of all natural disasters, flooding causes the greatest amount of economic and social damage. The United States' Federal Emergency Management Agency (FEMA) uses a number of hazard mitigation grant programmes for flood victims, including mitigation offers to relocate permanently repetitive flood loss victims. This study examines factors that help to explain the degree of difficulty repetitive flood loss victims experience when they make decisions about relocating permanently after multiple flood losses. Data are drawn from interviews with FEMA officials and a survey of flood victims from eight repetitive flooding sites. The qualitative and quantitative results show the importance of rational choices by flood victims in their mitigation decisions, as they relate to financial variables, perceptions of future risk, attachments to home and community, and the relationships between repetitive flood loss victims and the local flood management officials who help them. The results offer evidence to suggest the value of a more community–system approach to FEMA relocation practices.
Social impact of the 2004 Manawatu floods and the ‘hollowing out’ of rural New Zealand
Authors: Smith Willie , Davies‐Colley Christian , Mackay Alec , Bankoff Greg
Published: January 2011

The Manawatu floods of 2004 have had significant, long‐lasting social consequences. This paper draws on findings from a series of detailed surveys of 39 farm households directly affected by the floods and 17 individuals directly involved in managing the flood recovery programme. The nature of the impact on rural families highlights how the ‘hollowing out’ of rural New Zealand has changed the capacity of rural communities to respond to natural hazards and increased their sense of isolation. In addition, the floods exposed the vulnerability of rural communities. This is shown to have implications for policies designed to build resilience and improve responses to adverse events, including the need to support local, community initiatives on self‐reliance and mutual support. Approaches to manage better long‐term flood risks should be designed within a context of ongoing rural decline that has compromised the health of both individuals and communities.
Development of the Cognitive Dysfunction Questionnaire (CDQ) in a population based sample
Authors: VESTERGREN PETER , RÖNNLUND MICHAEL , NYBERG LARS , NILSSON LARS‐GÖRAN
Published: January 2011

Vestergren, P., Rönnlund, M., Nyberg, L. & Nilsson, L.‐G. (2011). Development of the Cognitive Dysfunction Questionnaire (CDQ) in a population based sample. Scandinavian Journal of Psychology52, 218–228.

The study reports on the development of a questionnaire for assessment of adult cognitive dysfunction (CDQ). Participants in a population‐based sample (65 ± 15 years, N = 370) responded to a 90‐item pilot version covering multiple aspects of memory/cognition. Based on exploratory principal components analyses and correlations with criterion measures of cognitive functioning (MMSE, Block Design, semantic/episodic memory), 20 items loading on 6 components were selected for the final version of the questionnaire. Cronbach’s α for the total score was 0.90. There was evidence of construct validity as judged by correlations between CDQ scores, objective cognitive measures, and a subjective memory measure (PRMQ). Discriminant validity was demonstrated by a low and non‐significant correlation with depressive symptoms. Further evidence of construct validity was provided by correlations with age and educational attainment. In conclusion, the CDQ is promising as a self‐rating screening tool for cognitive dysfunction, and will be the subject of further development and validation.
Sensory analysis of lipstick
Authors: Yap K. C. S. , Aminah A.
Published: January 2011

Synopsis

Sensory analysis of lipstick product by trained panellists started with recruiting female panels who are lipstick users, in good health condition and willing to be a part of sensory members. This group of people was further scrutinized with duo‐trio method using commercial lipstick samples that are commonly used among them. About 40% of the 15 panels recruited were unable to differentiate the lipstick samples they usually use better than chance. The balance of nine panels that were corrected at least with 65% across all trials in panels screening process was formed a working group to develop sensory languages as a means of describing product similarities and differences and a scoring system. Five sessions with each session took about 90 min were carried out using 10 types of lipsticks with different waxes mixture ratio in the formulation together with six commercial lipsticks that are the most common to the panels. First session was focus on listing out the panels’ perception towards the characteristic of the lipstick samples after normal application on their lips. Second session was focus on the refining and categorizing the responses gathered from the first session and translated into sensory attributes with its definition. Third session was focus on the scoring system. Fourth and fifth sessions were repetition of the third session to ensure consistency. In a collective effort of the panels, sensory attributes developed for lipstick were Spreadability, Off flavour, Hardness, Smoothness, Moist, Not messy, Glossy and Greasy. Analysis of variance was able to provide ample evidence on gauging the panel performance. A proper panels selecting and training was able to produce a reliable and sensitive trained panel for evaluating the product based on the procedures being trained.
Design and application of water‐in‐oil emulsions for use in lipstick formulations
Authors: Le Révérend B. J. D. , Taylor M. S. , Norton I. T.
Published: January 2011

Synopsis

The addition of water to lipsticks in the form of a water‐in‐oil emulsion is an attractive opportunity for cosmetics manufacturers to deliver hydrophilic molecules to the consumers, as well as improving the moisturizing properties. In this work, the effect of the emulsifier type and water content on the structural properties of the designed products was investigated. It has been shown that PGPR leads to smaller droplets than the other emulsifiers tested. This was attributed to the ability of PGPR to form elastic interfaces that slow the coalescence between droplets during the process. It was also observed that crystals of wax tend to form structures at the interface upon cooling that prevent coalescence during storage. These structures also prevent leakage of water into the continuous phase. No effect of the water content on the melting properties of the emulsions was observed. Upon addition of more than 10% water, softening of the material was measured, due to the overall decrease in solid content. Addition of crystalline material (hard paraffin) was successfully used to reinstate the material properties.
Online shopping among Chinese consumers: an exploratory investigation of demographics and value orientation
Authors: Wu Lingfei , Cai Yi , Liu Dehuan
Published: January 2011

The current study examined the relationship between Chinese consumers' personal value orientations and their Internet usage and online shopping behaviour. The study was based on responses from a sample of 1620 respondents in five cities in China. Based on Schwartz's value structure, four value orientations were identified and named as ‘openness to change orientation’, ‘self‐enhancement orientation’, ‘conservation orientation’ and ‘self‐transcendence orientation.’ Logistic regression analysis was used to investigate the relationship between respondents' demographics, socio‐economic characteristics, value orientations and their Internet usage and online shopping behaviour. Also, a structural equation modelling analysis was employed. ‘Openness to change orientation’ and ‘self‐enhancement orientation’ were found to have direct or indirect positive effect on respondents' online shopping behaviour; whereas ‘conservation orientation’ and ‘self‐transcendence orientation’ were not significant in the equation estimation.
The tyrosine phosphatase Shp‐2 interacts with the dopamine D1 receptor and triggers D1‐mediated Erk signaling in striatal neurons
Authors: Fiorentini Chiara , Mattanza Cinzia , Collo Ginetta , Savoia Paola , Spano PierFranco , Missale Cristina
Published: January 2011

J. Neurochem. (2011) 117, 253–263.

We report a novel mechanism for dopamine D1 receptor (D1R)‐mediated extracellular signal‐regulated kinases (Erk) activation in rat striatum. Erk signaling depends on phosphorylation and dephosphorylation events mediated by specific kinases and phosphatases. The tyrosine phosphatase Shp‐2, that is required for Erk activation by tyrosine kinase receptors, has been recently shown to regulate signaling downstream of few G protein‐coupled receptors. We show that the D1R interacts with Shp‐2, that D1R stimulation results in Shp‐2 tyrosine phosphorylation and activation in primary striatal neuronal cultures and that D1R/Shp‐2 interaction is required for transmitting D1R‐dependent signaling to Erk1/2 activation. D1R‐mediated Erk1/2 phosphorylation in cultured striatal neurons is in fact abolished by over‐expression of the inactive Shp‐2(C/S) mutant and by small interfering RNA‐induced Shp‐2 silencing. Moreover, by using selective inhibitors we show that both D1R‐induced Shp‐2 activation and Erk1/2 phosphorylation are dependent on the cyclic AMP/protein kinase A pathway and require Src. These results, which were substantiated also in transfected human embryonic kidney 293 cells, provide a novel mechanism by which to converge D1R signaling to the Erk pathway and suggest that Shp‐2 or the D1R/Shp‐2 interface could represent a potential drug target for disorders of dopamine transmission involving malfunctioning of D1R signaling.
Acetate supplementation attenuates lipopolysaccharide‐induced neuroinflammation
Authors: Reisenauer Chris J. , Bhatt Dhaval P. , Mitteness Dane J. , Slanczka Evan R. , Gienger Heidi M. , Watt John A. , Rosenberger Thad A.
Published: January 2011

J. Neurochem. (2011) 117, 264–274.

Glyceryl triacetate (GTA), a compound effective at increasing circulating and tissue levels of acetate was used to treat rats subjected to a continual 28 day intra‐ventricular infusion of bacterial lipopolysaccharide (LPS). This model produces a neuroinflammatory injury characterized by global neuroglial activation and a decrease in choline acetyltransferase immunoreactivity in the basal forebrain. During the LPS infusion, rats were given a daily treatment of either water or GTA at a dose of 6 g/kg by oral gavage. In parallel experiments, free‐CoA and acetyl‐CoA levels were measured in microwave fixed brains and flash frozen heart, liver, kidney and muscle following a single oral dose of GTA. We found that a single oral dose of GTA significantly increased plasma acetate levels by 15 min and remained elevated for up to 4 h. At 30 min the acetyl‐CoA levels in microwave‐fixed brain and flash frozen heart and liver were increased at least 2.2‐fold. The concentrations of brain acetyl‐CoA was significantly increased between 30 and 45 min following treatment and remained elevated for up to 4 h. The concentration of free‐CoA in brain was significantly decreased compared to controls at 240 min. Immunohistochemical and morphological analysis demonstrated that a daily treatment with GTA significantly reduced the percentage of reactive glial fibrillary acidic protein‐positive astrocytes and activated CD11b‐positive microglia by 40–50% in rats subjected to LPS‐induced neuroinflammation. Further, in rats subjected to neuroinflammation, GTA significantly increased the number of choline acetyltransferase (ChAT)‐positive cells by 40% in the basal forebrain compared to untreated controls. These data suggest that acetate supplementation increases intermediary short chain acetyl‐CoA metabolism and that treatment is potentially anti‐inflammatory and neuroprotective with regards to attenuating neuroglial activation and increasing ChAT immunoreactivity in this model.
REFLECTION ON FAMILY CONSENT: BASED ON A PREGNANT DEATH IN A BEIJING HOSPITAL
Authors: ZHANG XINQING
Published: January 2011

The ‘family consent’ process has been placed at the centre of Chinese clinical practice. Although there has been critical analysis of how the process functions in relation to the autonomy and rights of patients, there has been little examination of the perceptions and attitude of patients and their families and the medical professionals, in relation to moral dilemmas that arise in real cases in the bioethical discourse. When faced with a consent form in an emergency situation, the family member's capacity to act is reduced, as he/she becomes enmeshed in the hospital structure of tacit, socially‐imposed rules. In a questionnaires based on a real death case in 2008, 70.9% of the surveyed medical professionals (n = 3,665) disagreed with performing surgery without the consent of the family even if the patient's life was in danger, while 36.6% of the surveyed patients (n = 1,198) hold the same position. This work demonstrates the weakness of the family consent process as a safeguard of patient's autonomy. Finally, I argue that saving the patient's life should be the overriding obligation rather than the respect for the surrogate's autonomous choice at such a decisive moment.
On the Variation of Clamping Force in Bolted Double Lap Joints Subjected to Longitudinal Loading: A Numerical and Experimental Investigation
Authors: Chakherlou T. N. , Razavi M. J. , Aghdam A. B.
Published: January 2011

Abstract:  This study investigates the variation of clamping force and its concomitant effects on the performance of bolted double lap joints subjected to longitudinal loading. Two different amounts of clamping force were applied to bolted double lap joints made of Aluminium 2024‐T3, and variations of clamping force were measured under the application of longitudinal loading. Finite element modelling was also performed to compare with experiments. The results unanimously revealed a gradual initial reduction of clamping force followed by a significant increase as the longitudinal load was increased. Also affected, was the load transfer mechanism in the joint resulting in variation of friction force between the plates, but in a different trend compared to clamping force. Finally, the key parameters have been discussed and highlighted pertaining to the performance of the joint.