bluuebunny/crossref_metadata_2025 huggingface dataset:
GATA transcription factors directly regulate the Parkinson's disease-linked gene α-synuclein
Authors: Scherzer Clemens R. , Grass Jeffrey A. , Liao Zhixiang , Pepivani Imelda , Zheng Bin , Eklund Aron C. , Ney Paul A. , Ng Juliana , McGoldrick Meghan , Mollenhauer Brit , Bresnick Emery H. , Schlossmacher Michael G.
Published: August 2008

Increased α-synuclein gene (
SNCA
) dosage due to locus multiplication causes autosomal dominant Parkinson's disease (PD). Variation in
SNCA
expression may be critical in common, genetically complex PD but the underlying regulatory mechanism is unknown. We show that
SNCA
and the heme metabolism genes
ALAS2
,
FECH
, and
BLVRB
form a block of tightly correlated gene expression in 113 samples of human blood, where
SNCA
naturally abounds (validated
P
= 1.6 × 10
−11
, 1.8 × 10
−10
, and 6.6 × 10
−5
). Genetic complementation analysis revealed that these four genes are co-induced by the transcription factor GATA-1. GATA-1 specifically occupies a conserved region within
SNCA
intron-1 and directly induces a 6.9-fold increase in α-synuclein. Endogenous GATA-2 is highly expressed in substantia nigra vulnerable to PD, occupies intron-1, and modulates
SNCA
expression in dopaminergic cells. This critical link between GATA factors and
SNCA
may enable therapies designed to lower α-synuclein production.
Structural changes of membrane-anchored native PrP
C
Authors: Elfrink Kerstin , Ollesch Julian , Stöhr Jan , Willbold Dieter , Riesner Detlev , Gerwert Klaus
Published: August 2008

Misfolding and subsequent aggregation of endogeneous proteins constitute essential steps in many human disorders, including Alzheimer and prion diseases. In most prion protein-folding studies, the posttranslational modifications, the lipid anchor in particular, were lacking. Here, we studied a fully posttranslationally modified cellular prion protein, carrying two N-glycosylations and the natural GPI anchor. We used time-resolved FTIR to study the prion protein secondary structure changes when binding to a raft-like lipid membrane via its GPI anchor. We observed that membrane anchoring above a threshold concentration induced refolding of the prion protein to intermolecular β-sheets. Such transition is not observed in solution and is membrane specific. Excessive membrane anchoring, analyzed with molecular sensitivity, is thought to be a crucial event in the development of prion diseases.
Functional studies indicate amantadine binds to the pore of the influenza A virus M2 proton-selective ion channel
Authors: Jing Xianghong , Ma Chunlong , Ohigashi Yuki , Oliveira Fernando A. , Jardetzky Theodore S. , Pinto Lawrence H. , Lamb Robert A.
Published: August 2008

Influenza A and B viruses contain proton-selective ion channels, A/M2 and BM2, respectively, and the A/M2 channel activity is inhibited by the drugs amantadine and its methyl derivative rimantadine. The structure of the pore-transmembrane domain has been determined by both x-ray crystallography [Stouffer
et al.
(2008)
Nature
451:596–599] and by NMR methods [Schnell and Chou (2008)
Nature
451:591–595]. Whereas the crystal structure indicates a single amantadine molecule in the pore of the channel, the NMR data show four rimantadine molecules bound on the outside of the helices toward the cytoplasmic side of the membrane. Drug binding includes interactions with residues 40–45 with a polar hydrogen bond between rimantadine and aspartic acid residue 44 (D44) that appears to be important. These two distinct drug-binding sites led to two incompatible drug inhibition mechanisms. We mutagenized D44 and R45 to alanine as these mutations are likely to interfere with rimantadine binding and lead to a drug insensitive channel. However, the D44A channel was found to be sensitive to amantadine when measured by electrophysiological recordings in oocytes of
Xenopus laevis
and in mammalian cells, and when the D44 and R45 mutations were introduced into the influenza virus genome. Furthermore, transplanting A/M2 pore residues 24–36 into BM2, yielded a pH-activated chimeric ion channel that was partially inhibited by amantadine. Thus, taken together our functional data suggest that amantadine/rimantadine binding outside of the channel pore is not the primary site associated with the pharmacological inhibition of the A/M2 ion channel.
TGF-β signaling in dendritic cells is a prerequisite for the control of autoimmune encephalomyelitis
Authors: Laouar Yasmina , Town Terrence , Jeng David , Tran Elise , Wan Yisong , Kuchroo Vijay K. , Flavell Richard A.
Published: August 2008

One unresolved issue in immune tolerance is what prevents self-reactive T cells from activation. In this study, we used a transgenic mouse model of targeted functional inactivation of TGF-βR signaling in CD11c+cells (CD11cdnRmice) and showed a direct impact on the development of experimental autoimmune encephalomyelitis (EAE). We found that MOG35–55immunization of CD11cdnRmice results in strong inflammation of CNS, high frequency of T cells in CNS, increased levels of T helper 1 (TH1) and TH17 cytokines in the periphery, and lack of remission from EAE. Once crossed with mice prone to autoimmunity, double-transgenic CD11cdnRMogTCRmice revealed a spontaneous EAE-like disease characterized by early infiltration of activated myelin-specific T cells into CNS, activation of microglial cells, inflammation of CNS, dysfunction of locomotion, and premature death. We constructed chimeric mice and demonstrated that inactivation of TGF-βR signaling in dendritic cells (DCs) results in augmented EAE-associated T cell responses. Our data provide direct evidence that TGF-β can control autoimmunity via actions on DCs.
Educating the creative workforce: New directions for twenty‐first century schooling
Authors: McWilliam Erica , Haukka Sandra
Published: August 2008

This article sets out reasons for arguing that creativity is not garnish to the roast of industry or of education—i.e. the reasoning behind Mihalyi Csikszentmihalyi's insistence that creativity is not only about elites but involves everyone. This article investigates three key domains—scholarship, commerce and learning—to argue the importance of moving creativity from the margins of formal education to its centre. First, the article elaborates the scholarly work being done to bring definitional clarity to the concept of creativity, moving it from the realm of mystery, serendipity and individual genius to a definitional field that is more amenable to analysis. It then provides evidence about the extent to which creative capacity is being understood to be a powerful economic driver, not simply the province of the arts and the hobbyist. Finally, it examines new learning theory and its implications for formal education, noting both the possibilities and pitfalls in preparing young people for creative workforce futures.
Creativity and performativity: Counterpoints in British and Australian education
Authors: Burnard Pamela , White Julie
Published: August 2008

This article explores the complex interplay of power between performativity and creativity agendas—a mutual tension that resides in British and Australian education. Accountability constraints and conflicting policy debates are problematised against the wider imperatives of similar government agendas. This ‘counterpoint’ of freedom and control has significant implications for pedagogy and, through accommodating performativity, teacher agency and professionalism are under threat. The authors propose a ‘rebalancing’ where pedagogy transforms from a site of struggle for control, to one where a higher trust is placed in teacher professionalism. The idea of ‘rebalancing pedagogy’ offers a way for teachers to navigate and be supported through the opposing demands of performativity and creativity. It acknowledges the importance of teacher agency and where teaching is judged against the characteristics of a systemic approach that facilitates the building of creative learning communities capable of supporting any curricula or content‐focused programmes in and beyond schools.
A method for improving the dynamic simulation efficiency of underwater flexible structures by implementing non-active points in modelling
Authors: Lee Ji Hoon , Karlsen Ludvig , Lee Chun Woo
Published: August 2008

Lee, J. H., Karlsen, L., and Lee, C. W. 2008. A method for improving the dynamic simulation efficiency of underwater flexible structures by implementing non-active points in modelling. – ICES Journal of Marine Science, 65: 1552–1558. The implementation of non-active points into a conventional mass spring network for improving the simulation efficiency of fishing gear systems is presented. A conventional mass spring network generally consists of just active mass points involved in physical calculations, and non-active points located between neighbouring active mass points are not involved in the calculations. For each time-step, new positions for non-active points are calculated based on the active mass point positions already calculated for that time-step. By replacing some active mass points with non-active ones, computing time can be reduced while maintaining accuracy in the ground-interference simulation. As this method is more efficient in demonstrating the behaviour of fishing gear such as bottom longlines and bottom gillnets, an adaptive non-active point model represents the shape of a system more accurately than one consisting of just active mass points.
Laminin-511 is an epithelial message promoting dermal papilla development and function during early hair morphogenesis
Authors: Gao Jing , DeRouen Mindy C. , Chen Chih-Hsin , Nguyen Michael , Nguyen Ngon T. , Ido Hiroyuki , Harada Kenji , Sekiguchi Kiyotoshi , Morgan Bruce A. , Miner Jeffery H. , Oro Anthony E. , Marinkovich M. Peter
Published: August 2008

Hair morphogenesis takes place through reciprocal epithelial and mesenchymal signaling; however, the mechanisms controlling signal exchange are poorly understood. Laminins are extracellular proteins that play critical roles in adhesion and signaling. Here we demonstrate the mechanism of how laminin-511 controls hair morphogenesis. Dermal papilla (DP) from laminin-511 mutants showed developmental defects by E16.5, including a failure to maintain expression of the key morphogen noggin. This maintenance was critical as exogenous introduction of noggin or sonic hedgehog (Shh) produced downstream from noggin was sufficient to restore hair follicle development in lama5−/− (laminin-511-null) skin. Hair development required the β1 integrin binding but not the heparin binding domain of laminin-511. Previous studies demonstrated that Shh signaling requires primary cilia, microtubule-based signaling organelles. Laminin-511 mutant DP showed decreased length and structure of primary cilia in vitro and in vivo. Laminin-511, but not laminin-111, restored primary cilia formation in lama5−/− mesenchyme and triggered noggin expression in an Shh- and PDGF-dependent manner. Inhibition of laminin-511 receptor β1 integrin disrupted DP primary cilia formation as well as hair development. These studies show that epithelial-derived laminin-511 is a critical early signal that directs ciliary function and DP maintenance as a requirement for hair follicle downgrowth.
A branched-chain fatty acid is involved in post-embryonic growth control in parallel to the insulin receptor pathway and its biosynthesis is feedback-regulated in C. elegans
Authors: Kniazeva Marina , Euler Tanya , Han Min
Published: August 2008

Growth and development of multicellular organisms are controlled by signaling systems that sense nutrition availability and metabolic status. We report a novel and surprising factor in Caenorhabditis elegans development, the monomethyl branched-chain fatty acid C17ISO, a product of leucine catabolism. We show here that C17ISO is an essential constituent in a novel mechanism that acts in parallel with the food-sensing DAF-2 (insulin receptor)/DAF-16 (FOXO) signaling pathway to promote post-embryonic development, and that the two pathways converge on a common target repressing cell cycle. We show that C17ISO homeostasis is regulated by a SREBP-1c-mediated feedback mechanism that is different from the SREBP-1c-mediated regulation of common fatty acid biosynthesis, as well as by peptide uptake and transport. Our data suggest that C17ISO may act as a chemical/nutritional factor in a mechanism that regulates post-embryonic development in response to the metabolic state of the organism.
Genomic medicine in Mexico: Initial steps and the road ahead
Authors: Jimenez-Sanchez Gerardo , Silva-Zolezzi Irma , Hidalgo Alfredo , March Santiago
Published: August 2008

Mexico faces important demographic and epidemiological transitions with significant implications to patterns of disease, disability, and death. On the one hand, there are problems of underdevelopment and, on the other, the emerging challenges of the chronic and degenerative diseases of the industrialized world. For these diseases, prevention becomes a key strategy for alleviating a major burden to the economy and health of the Mexican population. Genomic medicine has become a priority to the Mexican government as a means of finding new strategies to tackle common diseases. In 2000, strategic planning for genomic medicine began, from a feasibility study and a multi-institutional consortium effort, to the creation of a National Institute of Genomic Medicine by the Mexican congress in 2004. Current research programs in genomic medicine in Mexico include the construction of a haplotype map of the Mexican population, several genome-wide association studies for common diseases, such as diabetes, obesity, cardiovascular disease, and cancer, as well as translational medicine projects that include biomarkers discovery for several kinds of cancer, pharmacogenomics, and nutrigenomics. Although this strategy has been successful, there are challenges that still need to be addressed, including increased investment in science and technology to stimulate a more vigorous and competitive research environment, development of more effective basic and clinical research synergies, recruitment and training of more human resources in genomic medicine, developing mechanisms to stimulate translational research, and developing a more modern regulatory framework to ensure that genomic medicine will successfully contribute to improve healthcare in the Mexican population.
Phage-Display Methodology for the Study of Protein-Protein Interactions: Stage 1, Generating Libraries
Authors: Goodyear Carl S. , Silverman Gregg J.
Published: August 2008

INTRODUCTION

This method for creation of phage libraries can be used for the generation and/or engineering of variant protein domains. It was adapted in our laboratory for the development of variant domains of SpA (the virulence factor, protein A, produced by clinical isolates of Staphylococcus aureus) with novel Fab-binding specificities. Specifically, we used this protocol to generate libraries of domains in which we randomized six to eight codons that define the natural VH3 specificity of SpA. In our effort, these codons were variegated using the NNK or VNS doping strategy. Toward this goal, three large (60- to 88-residue) oligonucleotides with targeted degenerate codons were designed. To facilitate construction of the composite domain library, these oligonucleotides had overlapping complementary stretches of at least 12 nucleotides. Of course, for application to other domains, the number and composition of the required oligonucleotides are dependent on the specific variant domains to be generated. This protocol details Stage 1 of the method, the generation of a phage library via overlap PCR and bacterial cloning. The initial PCR amplification requires the mixing of equimolar amounts of two oligonucleotides to form a template for the subsequent PCR.
Testing assumptions of mark–recapture theory in the coral reef fish Lutjanus apodus
Authors: Wormald C. L. , Steele M. A.
Published: August 2008

This study tested assumptions of the Cormack–Jolly–Seber capture–mark–recapture (CMR) model in a population of the tropical snapper Lutjanus apodus in the central Bahamas using a combination of laboratory and field studies. The suitability of three different tag types [passive integrated transponder (PIT) tag, T‐anchor tag and fluorescent dye jet‐injected into the fins] was assessed. PIT tags were retained well, whereas T‐anchor tags and jet‐injected dye were not. PIT tags had no detectable effect on the rates of growth or survival of individuals. The capture method (fish trapping) was found to provide a representative sample of the population; however, a positive trap response was identified and therefore the assumption of equal capture probability was violated. This study illustrates an approach that can be used to test some of the critical assumptions of the CMR theory and it demonstrates that CMR methods can provide unbiased estimates of growth and mortality of L. apodus provided that trap response is explicitly modelled when estimating survival probability.
Parasites as biological tags for stock discrimination of the Brazilian flathead Percophis brasiliensis in the south‐west Atlantic
Authors: Braicovich P. E. , Timi J. T.
Published: August 2008

Three stocks of the Brazilian flathead Percophis brasiliensis were identified on the coast of Argentina and Uruguay using parasites as biological tags. A total of 177 fish were examined and 23 parasite species were found. Fish were caught in four zones: north of the Argentine–Uruguayan Common Fishing Zone (34°30′–36°30′ S; 53°30′–56°00′ W), south of the Argentine–Uruguayan Common Fishing Zone (38°08′ S 57°32′ W), El Rincón zone (39–41° S; 60–62° W) and San Matías Gulf (41°40′–42°10′ S; 63°50′–65°00′ W). Discriminant analyses allowed the identification of three discrete stocks in the four zones (86·44% of classified samples were correctly identified), with P. brasiliensis from both north and south of the Argentine–Uruguayan Common Fishing Zone clumping together, as a single stock. Some species were important in discriminating among groups, Anisakis simplex was related to southern areas, while Grillotia sp., Corynosoma australe and Hysterothylacium sp. were important in determining the position of fish from the Argentine–Uruguayan Common Fishing Zone. These results were corroborated by comparing parasite prevalence and abundance among zones. The main differences were observed in those comparisons involving fish from the San Matías Gulf. Fish from the Argentine–Uruguayan Common Fishing Zone were characterized by higher infections of Grillotia sp., C. australe, Corynosoma cetaceum and Hysterothylacium sp., while the samples from El Rincón and San Matías Gulf showed higher infections of A. simplex. Samples from San Matías Gulf were characterized by lower levels of parasitism for all other species. Differences in environmental factors and their influence on the distribution of zooplankton and other hosts in the food web may be differentially shaping the parasite community structure in each zone, resulting in identifiable stocks of the P. brasiliensis. The present study confirmed the existence of regional biological tags that delineated fish assemblages.
Sneaky egg‐eating in Telmatherina sarasinorum, an endemic fish from Sulawesi
Authors: Gray S. M. , McKinnon J. S. , Tantu F. Y. , Dill L. M.
Published: August 2008

Observations of a novel behavioural tactic employed by egg‐eating male Telmatherina sarasinorum are described. Four T. sarasinorum males were observed actively courting females of closely related Telmatherina antoniae, enticing the female to spawn, and then eating the eggs. The possible evolutionary implications of sneaky egg‐eating behaviour are discussed.
Feeding ecology and growth of neonate and juvenile blacktip sharks Carcharhinus limbatus in the Timbalier–Terrebone Bay complex, LA, U.S.A.
Authors: Barry K. P. , Condrey R. E. , Driggers W. B. , Jones C. M.
Published: August 2008

Stomach contents and vertebrae from neonate and juvenile blacktip sharks Carcharhinus limbatus (n= 334) were examined to describe their diet, feeding patterns and growth within the Timbalier–Terrebone Bay complex, LA, U.S.A. In the study area, both neonate and juvenile C. limbatus feed primarily on gulf menhaden Brevoortia patronus. However, based on the index of relative importance (IRI), gulf menhaden constituted a larger portion of the diet of neonates (84·05 %IRI) than for juveniles (47·91 %IRI). An increase in the index of relative fullness between the afternoon and dusk time intervals and a large decrease in the percentage of empty stomachs between the night and early morning time intervals suggested that these fish exhibited a diel feeding pattern with crepuscular periods being the times of highest feeding activity. A higher percentage of empty stomachs (neonates 68% and juveniles 39%) and a significantly lower growth rate (age 0+ year C. limbatus, 0·62 mm day−1; age 1+ year fish, 0·89 mm day−1) could indicate that neonate C. limbatus are less efficient predators than older conspecifics.
Metazoan parasites of the thumb grenadier Nezumia pulchella, from the south‐eastern Pacific, off Chile, and their use for discrimination of host populations
Authors: Salinas X. , González M. T. , Acuña E.
Published: August 2008

The parasite communities of Nezumia pulchella across its geographical range in the south‐eastern Pacific were described, from 217 fish captured from four localities in northern and central Chile (24° S to 33° S). Five ectoparasites and 13 endoparasites were recorded and the highest prevalence and intensity of infection was found for the copepods Jusheyhoea macrura and Clavella sp. 1, for the monogenean Diclidophora sp. and for the larval acanthocephalan Corynosoma australe. Parasite species richness decreased with latitude. Multivariate discriminant analysis and correspondence analysis supported the use of parasites of N. pulchella to discriminate populations of this host, suggesting the existence of three well‐defined host populations in the geographical range examined. Jusheyhoea macrura, C. australe, Lophoura sp., Diclidophora sp., Capillaria sp. and Proleptus sp. were the most important species for discriminant analysis.
The carboxylation efficiency of the vitamin K‐dependent clotting factors: studies with factor IX
Authors: BLOSTEIN M. , CUERQUIS J. , LANDRY S. , GALIPEAU J.
Published: August 2008

Summary.  Haemophilia B is characterized by a deficiency of the γ‐carboxylated protein, factor IX (FIX). As a first step to optimize a gene therapy strategy to treat haemophilia B, we employed a previously described approach (Biochemistry 2000;39: 14322) of altering the propeptide of vitamin K‐dependent proteins in vitro, to improve the carboxylation efficiency of FIX. Both native FIX and FIX with a prothrombin propeptide (proPT‐FIX) produced recombinant FIX in vitro following transfection of their cDNAs into human embryonic kidney (HEK) 293 cells. Using hydroxyapatite chromatography to separate carboxylated from uncarboxylated FIX, we are able to show that >90% of FIX is γ‐carboxylated and that substituting the propeptide of prothrombin into FIX does not further increase the relative amounts of carboxylated material. These results demonstrate that the nature of the propeptide, per se is not the sole determinant of optimal carboxylation of FIX in our expression system in HEK 293 cells.
Learning as an empowerment process in breast cancer self‐help groups
Authors: Stang Ingun , Mittelmark Maurice B
Published: August 2008

Aim.  This intervention study aimed to promote and examine empowerment processes in women recovering from breast cancer and participating in self‐help groups.

Background.  Feelings of powerlessness may follow from being diagnosed and treated for breast cancer. In theory, self‐help groups may stimulate empowerment, which stands in contrast to powerlessness, by increasing the participants’ sense of control. Professional assistance may contribute positively, by assuring that the issue of empowerment is addressed.

Design.  The study had an intervention design based on the ideas of empowerment and self‐help. Three professionally led self‐help groups were established. The groups ran sequentially and met weekly for approximately four months.

Methods.  Eighteen women in groups of 5–7 participated in self‐help group discussions and also in focus group interviews, which provided the main study data. Each group was interviewed three times. Observation data provided a basis for comprehension of the groups’ culture, relationships and processes.

Results.  Learning appeared as one of three salient components in empowerment processes in the self‐help groups. This learning component consists of four elements: consciousness‐raising, acquisition of objective knowledge, learning from others’ experiences and discovery of new perspectives in life and in oneself.

Conclusions.  The study shows that self‐help groups focusing on empowerment issues made a valuable contribution to recovery and are strongly recommended by the participants.

Relevance to clinical practice.  This study suggests that best practice, for those who manage self‐help programmes of all types, may be to arrange for empowerment to be an explicit aspect of the intervention, guided by professionals with training in group facilitation and knowledgeable about the facilitation of empowerment in particular.
Depression in adults with intellectual disability: symptoms and challenging behaviour
Authors: Hurley A. D.
Published: August 2008

Background  Psychiatric evaluation of adults with intellectual disability (ID) remains complex because of limitations in verbal abilities, atypical clinical presentation and challenging behaviour. This study examines the clinical presentation of adults with depression compared with bipolar disorder, anxiety disorders and non‐psychiatric control patients.

Method  This study is a retrospective record review of the initial psychiatric diagnostic evaluation for 300 adult patients with ID drawn from a clinic population. Patients with major depression (n = 85) were compared with those with bipolar disorder (n = 70), anxiety disorders (n = 30) and control patients without psychiatric disorder (n = 27). Key symptoms of depression assessed during the interview were examined as well as challenging behaviour.

Results  Three symptoms were useful in differentiating depressed patients from all other groups: sad mood, crying, and anhedonia. Withdrawal, suicidality, and awakening during the night were significant compared with anxiety patients and controls; however, few patients reported suicidality. Bipolar patients were significantly different from depressed patients for elevated mood, acute anger episodes, increase in verbalization, pressure of speech, talk of sexual themes, increase in appetite and poor concentration. Anxiety patients had more fearfulness without withdrawal, sad mood, crying, anhedonia and suicidality. Challenging behaviour was most pronounced in bipolar patients; for depressed patients, aggression and impulsivity were significant compared with anxiety patients and controls. Overall, the control patients presented with few symptoms in any category.

Conclusions  Sad mood, crying and anhedonia are key significant features of depression. Most patients with ID cannot meet the required number of DSM criteria or suggested DM‐ID adapted criteria for major depression. Many depressive symptoms were reported in modest numbers and this was probably related to deficiencies in self‐report or observational skills of caregivers. Challenging behaviour is not diagnostically specific. It is, however, a key atypical feature of depression.
Farmers' Perceptions on Rice Varieties in Sikasso Region of Mali and their Implications for Rice Breeding
Authors: Efisue A. , Tongoona P. , Derera J. , Langyintuo A. , Laing M. , Ubi B.
Published: August 2008

Rice is an important staple food and cash crop. Although many varieties of rice have been developed to date, few are adopted possibly because researchers did not take into account farmers’ preferences and perceptions on varieties during the development process. Because farmers increasingly rely on low‐yielding landraces, production fails to meet demand. To provide an understanding of farmers’ preferences for rice cultivars and perceptions on drought stress and management practices as inputs to rice breeding research, this study was conducted in the Sikasso region of Mali in September 2005 using participatory rural appraisal approach. A total number of 125 farmers were randomly selected from 10 villages in three ecologies and interviewed individually and in groups. Results showed that farmers’ preferences, crop management practices and ranking of production constraints differed significantly across ecologies. Whereas farmers in the irrigated ecologies preferred high‐yielding, long duration rice varieties, those in the upland and lowland ecologies preferred tall plants of short duration. While upland and lowland farmers preferred red and white long grains, respectively, irrigated ecologies were indifferent about grain colour. Farmers appeared willing to trade‐off yield for grain quality and plant height, inconsistent with traditional breeders’ selection criteria. The high preference for tall varieties among farmers in the upland and lowland ecologies also contrasted sharply with the model of dwarf rice varieties responsible for the green revolution in Asia. The implication of these findings for rice breeders is that different plant idiotypes complemented by effective drought management practices should target different ecologies to increase impact.
Cardiovascular autonomic dysfunction predicts acute ischaemic stroke in patients with Type 2 diabetes mellitus: a 7‐year follow‐up study
Authors: Ko S. H. , Song K. H. , Park S. A. , Kim S. R. , Cha B. Y. , Son H. Y. , Moon K. W. , Yoo K. D. , Park Y. M. , Cho J. H. , Yoon K. H. , Ahn Y. B.
Published: August 2008

Aims  We investigated whether cardiovascular autonomic neuropathy (CAN) is associated with acute ischaemic stroke in patients with Type 2 diabetes.

Methods  From 1999 to 2000, cardiovascular autonomic function tests were conducted in patients with Type 2 diabetes (n = 1458). Patients were followed up between 2006 and 2007. Standard tests for CAN measured heart rate variability parameters [expiration‐to‐inspiration (E/I) ratio, responses to the Valsalva manoeuvre and standing]. Using the American Diabetes Association criteria, the CAN scores were determined from the results of each test as follows: 0 = normal, 1 = abnormal (total maximum score 3). We assessed the development of acute ischaemic stroke events.

Results  The prevalence of CAN at baseline was 55.7% (E/I 17.1%, Valsalva 39.4%, posture 27.3%) (n = 1126). During follow‐up, 131 patients (11.6%) developed acute ischaemic stroke. The vascular events were more frequent in older patients (P < 0.001) and in those with diabetes of longer duration (P = 0.022), hypertension (P < 0.001) or diabetic retinopathy (P = 0.03) than in patients without vascular events. Patients with ischaemic stroke had higher creatinine levels (P = 0.045) and higher urine albumin excretion (P = 0.025) than those of patients without stroke. Cox proportional hazard regression analysis revealed that the CAN score was associated with the development of acute ischaemic stroke (total score 0 vs. 3, adjusted hazard ratio 2.7, 95% CI 1.3–5.5, P = 0.006).

Conclusion  Cardiovascular autonomic dysfunction was significantly associated with the development of ischaemic stroke in patients with Type 2 diabetes.
RELIGIOUS CULTURE AND HISTORICAL CHANGE: VATICAN II ON RELIGIOUS FREEDOM
Authors: FARRELLY M. JOHN
Published: August 2008

At Vatican II and since Vatican II there have been Catholics who have held that the Council's teaching on religious freedom is in contradiction to the Church's earlier teaching and practice. The Council defended it as a legitimate development of doctrine in part through claiming that changing human experience in history shows us only gradually what human dignity entails, and the Church learns from this experience. True, the Council's teaching is in part a denial of its earlier teaching and practice. The present article defends the legitimacy of this development through showing that there is a change of paradigm by which the Church now views this issue, a change that includes both continuity and discontinuity. This reliance on what is revealed to us by changing human experience is accepted by the Church only when it sees it as critically evaluated by an adequate philosophy and as in accord with Christian revelation, but its acceptance moves us to a growth in our understanding of revelation itself.
‘May we please have sex tonight?’– people with learning difficulties pursuing privacy in residential group settings
Authors: Hollomotz Andrea ,   The Speakup Committee
Published: August 2008

Accessible summary

Everyone has the right to privacy and relationships.

Some people who live in group homes are not allowed to be private with their partner.

We will explain how this makes us feel.

We will say what should change.

Parts written in ‘bold’ font are in plain English. Read them to find out more.

Many residential group settings for people with learning difficulties do not provide individuals with the private space in which they can explore their sexual relationships in a safe and dignified manner. Lack of agreed private spaces seriously infringes the individual’s human rights. Many people with learning difficulties who lack privacy have no other option but to escape to isolated public or semi‐private spaces to be sexually active. This places individuals at risk. It is suggested that self‐advocacy driven policy guidance must be developed which must require residential services to review their practice to ensure that they accommodate residents’ need for privacy, whilst supporting them to lead safe sexual relationships.
The different forms of PNS myelin P0 protein within and outside lipid rafts
Authors: Fasano Anna , Amoresano Angela , Rossano Rocco , Carlone Giulia , Carpentieri Andrea , Liuzzi Grazia Maria , Pucci Piero , Riccio Paolo
Published: August 2008

It is now well established that plasma membranes, such as the myelin sheath, are made of different microdomains with different lipid and protein composition. Lipid rafts are made mainly of sphingolipids and cholesterol, whereas the non‐raft regions are made mainly of phosphoglycerides. Most myelin proteins may distribute themselves in raft and non‐raft microdomains but the driving force that gives rise to their different distribution is not known yet. In this paper, we have studied the distribution of protein zero (P0), the most representative protein of PNS myelin, in the membrane microdomains. To this end, we have purified P0 from both non‐raft (soluble P0, P0‐S) and raft (P0‐R) regions of PNS. Purified proteins were analyzed by two‐dimensional gel electrophoresis and identified and characterized by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. A detailed structural description of the two P0 forms is given in terms of amino acid sequence, post‐translational modifications, and composition of associated lipids. Our findings suggest that structural differences between the two proteins, mainly related to the glycogroups, might be responsible for their different localization.
Lysophosphatidic acid‐induced membrane ruffling and brain‐derived neurotrophic factor gene expression are mediated by ATP release in primary microglia
Authors: Fujita Ryousuke , Ma Yan , Ueda Hiroshi
Published: August 2008

We examined the effects of lysophosphatidic acid (LPA) on microglia, which may play an important role in the development and maintenance of neuropathic pain. LPA caused membrane ruffling as detected by scanning electron microscopy, and increased the expression of brain‐derived neurotrophic factor (BDNF) in a primary culture of rat microglia, which express LPA3, but not LPA1or LPA2receptors. These actions were inhibited by a Gαq/11‐antisense oligodeoxynucleotide (AS‐ODN), U73122, an inhibitor of phospholipase C (PLC), and apyrase, which specifically degrades ATP and ADP. When ATP release was measured using a luciferin‐luciferase bioluminescence assay, LPA was shown to increase it in an LPA3and PLC inhibitor‐reversible manner. However, LPA‐induced ATP release was also blocked by the Gαq/11AS‐ODN, but not by pertussis toxin. These results suggest that LPA induces the release of ATP from rat primary cultured microglia via the LPA3receptor, Gαq/11and PLC, and that the released ATP or ectopically converted ADP may in turn cause membrane ruffling via P2Y12receptors and Gαi/oactivation, and BDNF expression via activation of P2X4receptors.
Modest loss of peripheral axons, muscle atrophy and formation of brain inclusions in mice with targeted deletion of gigaxonin exon 1
Authors: Dequen Florence , Bomont Pascale , Gowing Geneviève , Cleveland Don W. , Julien Jean‐Pierre
Published: August 2008

Mutations in the gigaxonin gene are responsible for giant axonal neuropathy (GAN), a progressive neurodegenerative disorder associated with abnormal accumulations of Intermediate Filaments (IFs). Gigaxonin is the substrate‐specific adaptor for a new Cul3‐E3‐ubiquitin ligase family that promotes the proteasome dependent degradation of its partners MAP1B, MAP8 and tubulin cofactor B. Here, we report the generation of a mouse model with targeted deletion of Gan exon 1 (GanΔexon1;Δexon1). Analyses of the GanΔexon1;Δexon1 mice revealed increased levels of various IFs proteins in the nervous system and the presence of IFs inclusion bodies in the brain. Despite deficiency of full length gigaxonin, the GanΔexon1;Δexon1 mice do not develop overt neurological phenotypes and giant axons reminiscent of the human GAN disease. Nonetheless, at 6 months of age the GanΔexon1;Δexon1 mice exhibit a modest hind limb muscle atrophy, a 10% decrease of muscle innervation and a 27% axonal loss in the L5 ventral roots. This new mouse model should provide a useful tool to test potential therapeutic approaches for GAN disease.
Candida albicans, a distinctive fungal model for cellular aging study
Authors: Fu Xiao‐Hong , Meng Fei‐Long , Hu Yan , Zhou Jin‐Qiu
Published: August 2008

The unicellular eukaryotic organisms represent the popular model systems to understand aging in eukaryotes. Candida albicans, a polymorphic fungus, appears to be another distinctive unicellular aging model in addition to the budding yeast Saccharomyces cerevisiae and fission yeast Schizosaccharomyces pombe. The two types of Candida cells, yeast (blastospore) form and hyphal (filamentous) form, have similar replicative lifespan. Taking the advantage of morphologic changes, we are able to obtain cells of different ages. Old Candida cells tend to accumulate glycogen and oxidatively damaged proteins. Deletion of the SIR2 gene causes a decrease of lifespan, while insertion of an extra copy of SIR2 extends lifespan, indicating that like in S. cerevisiae, Sir2 regulates cellular aging in C. albicans. Interestingly, Sir2 deletion does not result in the accumulation of extra‐chromosomal rDNA molecules, but influences the retention of oxidized proteins in mother cells, suggesting that the extra‐chromosomal rDNA molecules may not be associated with cellular aging in C. albicans. This novel aging model, which allows efficient large‐scale isolation of old cells, may facilitate biochemical characterizations and genomics/proteomics studies of cellular aging, and help to verify the aging pathways observed in other organisms including S. cerevisiae.
Molecular genetic analysis for the Bx subgroup revealing two novel alleles in the ABO gene
Authors: Cai Xiao‐Hong , Jin Sha , Liu Xi , Shen Wei , Lu Qiong , Wang Jian‐Lian , Fan Liang‐Feng , Sun Ji‐Li , Liu Da‐Zhuang , Xiang Dong
Published: August 2008

BACKGROUND: Bx is a very rare ABO blood group phenotype and the molecular mechanism underlying it still remains largely unknown. This study reports two novel Bx alleles in two Chinese individuals.

STUDY DESIGN AND METHODS: Serologic investigations including serum transferase activity assay were performed with standard methods. DNA sequences of all seven exons and exon‐intron boundaries of ABO gene were analyzed using genomic DNA by polymerase chain reaction and direct DNA sequencing or sequencing after gene cloning.

RESULTS: Bx phenotypes were diagnosed in these two individuals. DNA analysis revealed that the ABO gene of the two Bx individuals was heterozygous of O01/B alleles. Two novel heterozygous mutations 905A>G and 541T>C were identified, respectively, which resulted in the amino acid changes D302G and W181R in the B glycosyltransferases. The mutations were not found in 120 randomly selected samples.

CONCLUSION: Amino acid substitutions resulted from novel mutations 905A>G and 541T>C on ABO gene change highly conserved regions of the enzyme and may reduce the activity of the glycosyltransferases, leading to the Bx phenotype.
Magnetic and Electrical Properties of (Mn, La)‐Codoped SrTiO3 Thin Films
Authors: Zhang Song‐Yin , Lin Yuan‐Hua , Nan Ce‐Wen , Zhao Rongjuan , He Jinliang
Published: August 2008

Mn‐doped SrTiO3‐based thin films have been prepared by a simple sol–gel spin‐coating method on silicon substrate. X‐ray diffraction and high‐resolution transmission electron microscopy reveal that these thin films are composed of amorphous and crystalline SrTiO3 phases. Optical and electrical measurements indicate that La codoping can make the band gap of SrTiO3 narrow and cause the leakage current to increase. Ferromagnetic behavior can be observed in these Mn‐ and/or La‐codoped SrTiO3‐based thin films at room temperature, which should be ascribed to the magnetic coupling between the induced free electrons and Mn 3d spins.
The four and a half LIM domain protein 2 interacts with and regulates the HERG channel
Authors: Lin Jijin , Lin Shuguang , Yu Xiyong , Choy Patrick C. , Shen Xiuzhang , Deng Chunyu , Kuang Sujuan , Wu Jun
Published: August 2008

Protein–protein interactions are critical for protein trafficking, localization and the regulation of ion channels. The human ether‐a‐go‐go‐related gene (herg) encodes the α‐subunit of the potassium channel underlying the rapid component of the cardiac delayed rectifier current. To identify the cellular proteins involved in the regulation of the HERG channel, a human heart cDNA library was screened using a yeast two‐hybrid system, with the N‐terminus of HERG as bait. The four and a half LIM domain protein 2 (FHL2) was identified as a potential HERG partner. The interaction between these two proteins was confirmed by co‐immunoprecipitation and glutathione transferase pull‐down assays and immunocytochemical analysis. The physiological implication of HERG–FHL2 interaction, assessed by whole‐cell, patch‐clamp electrophysiology experiments, showed a significant increase in the HERG current amplitude and a faster deactivation of the tail current in human embryonic kidney 293 cells co‐expressing HERG and FHL2. These data indicate that FHL2 interacts with and regulates the HERG channel. Our findings may aid in the further understanding of the molecular basis of HERG channel diversity and arrhythmogenesis in the long‐QT syndrome.
Investigation of CTLA‐4 and CD28 gene polymorphisms in a group of Turkish patients with colorectal cancer
Authors: Dilmec F. , Ozgonul A. , Uzunkoy A. , Akkafa F.
Published: August 2008

Colorectal cancer (CRC), also called colon cancer or bowel cancer, includes cancerous growths in the colon, rectum and appendix. The immune system is an important defence mechanism against cancer and is often dysfunctional in patients with malignancies. Cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4) and CD28 genes encode receptors that provide negative and positive signals, respectively. Polymorphisms in these genes can affect their functions. In this study, we aimed to investigate the association of cancer with the frequencies and roles of CTLA‐4/+49A > G (exon 1) and –318C > T (promoter), and CD28/IVS3 + 17T > C (intron 3 position + 17). These polymorphisms were genotyped using polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) in 218 Turkish subjects (56 patients with CRC and 162 healthy controls). No statistically significant differences in the genotype distributions of CTLA‐4/+49GG (1.8% vs. 6.8%, odds ratio (OR) = 0.250, P = 0.305) and CTLA‐4/−318TT (0% vs. 0.6%, OR = 1.006, P = 1.000), and CD28/IVS3 + 17CC (8.9% vs. 3.7%, OR = 0.2411, P = 0.155) between patients with CRC and healthy controls, were observed. We also found that there were no significant differences in the frequencies of CTLA‐4/+49G (18.8% vs. 20.1%, OR = 0.920, P = 0.891) and CTLA‐4/−318T (7.1% vs. 4.3%, OR = 1.653, P = 0.314), and CD28/IVS3 + 17C alleles (25.9% vs. 19.1%, OR = 1.353, P = 0.139) between two study groups. Present results suggested that CTLA‐4 and CD28 gene polymorphisms did not play an important role in Turkish patients with CRC.
FCER1A gene proximal promoter polymorphisms in Caucasians and East Asians
Authors: Potaczek D. P. , Sanak M. , Nishiyama C. , Okumura K. , Ogawa H. , Szczeklik A.
Published: August 2008

Two FCER1A gene proximal promoter polymorphisms, –344C > T and –95T > C, both associated with total serum IgE and/or allergic disorders in Caucasians and East Asians, were shown to influence the gene expression in additive manner. In face of the rarity of other proximal promoter variants in Caucasians or their lack in East Asians, future investigations of the FCER1A locus in these ethnic groups should probably focus on three common haplotypes of the common –344C > T and –95T > C polymorphisms.
Genetic Diversity and Association Analysis for Salinity Tolerance, Heading Date and Plant Height of Barley Germplasm Using Simple Sequence Repeat Markers
Authors: Eleuch Lilia , Jilal Abderrazek , Grando Stefania , Ceccarelli Salvatore , Von Korff Schmising Maria , Tsujimoto Hisashi , Hajer Amara , Daaloul Abderrazek , Baum Michael
Published: August 2008

The objective of this study was to investigate the genetic diversity of barley accessions. Additionally, association trait analysis was conducted for grain yield under salinity, heading date and plant height. For this purpose, 48 barley genotypes were analyzed with 22 microsatellite simple sequence repeat (SSR) markers. Four of the 22 markers (Bmac316, scssr03907, HVM67 and Bmag770) were able to differentiate all barley genotypes. Cluster and principal coordinate analysis allowed a clear grouping between countries from the same region. The genotypes used in this study have been evaluated for agronomic performance in different environments. Conducting association analysis for grain yield under salinity conditions using TASSEL software revealed a close association of the marker Bmag749 (2H, bin 13) in two different environments with common significant alleles (175, 177), whereas the HVHOTR1 marker (2H, bin 3) was only significant in Sakhar_Egypt with alleles size being 158 and 161. Heading date also showed an association with scssr03907 through the common significant specific allele 111 and EBmac0415 markers in three different agro climatic locations, whereas HVCMA, scssr00103 and HVM67 were linked to heading date in the Egyptian environment only. The plant height association analysis revealed significant markers Bmag770 via the significant allele 152 and scssr09398.