bluuebunny/crossref_metadata_2025 huggingface dataset:
Cortex‐ and striatum‐ derived neural stem cells produce distinct progeny in the olfactory bulb and striatum
Authors: Willaime‐Morawek Sandrine , Van Der Kooy Derek
Published: April 2008

Neural stem cells can be isolated from the mouse embryonic cortex but do not persist in the adult cortex. In contrast, neural stem cells from the striatal embryonic germinal zone persist in the adult subependyma. Emx1‐lineage analysis revealed that cortex‐derived neural stem cells survive and migrate ventrally into the subependyma where they intermix with the host striatal neural stem cells [S. Willaime‐Morawek et al. (2006)J. Cell Biol. 175, 159–168]. Cortex‐derived cells proliferate faster in the subependyma and reach the olfactory bulb earlier than striatum‐derived cells. In the olfactory bulb, cortex‐derived cells produce more cells and more dopaminergic neurons in the glomerular layer than striatum‐derived cells. Cortex‐derived cells also give rise to more astrocytes and less neurons in the striatum than striatum‐derived cells. Thus, history matters; cortex‐derived neural stem cells in the subependyma give rise to progeny in the olfactory bulb and striatum but in different proportions than striatum‐derived neural stem cells.
Down‐regulation of insulin‐degrading enzyme by presenilin 1 V97L mutant potentially underlies increased levels of amyloid beta 42
Authors: Qin Wei , Jia Jianping
Published: April 2008

Amyloid beta (Aβ)42 plays a pivotal role in Alzheimer's disease. We previously reported a novel presenilin (PS)1 mutant (V97L) that was expressed in related patients with early onset Alzheimer's disease. We found that patients with the V97L mutation had increased levels of extracellular and intracellular Aβ42. Here we found that the increased extracellular level of Aβ42 was always accompanied by a reduction of insulin‐degrading enzyme (IDE) activity on the plasma membranes. However, increase of intracellular Aβ42 was associated with decreased expression and activity of IDE in the cytosol and endoplasmic reticulum in the PS1 V97L mutant‐transfected human SH‐SY5Y cell line. These studies indicate that pathological levels of Aβ42 may be caused by the negative effects of PS1 (V97L) on IDE expression and activity. Our findings provide evidence for the molecular basis of familial Alzheimer's disease pathogenesis.
Chronic cold exposure increases RGS7 expression and decreases α2‐autoreceptor‐mediated inhibition of noradrenergic locus coeruleus neurons
Authors: Jedema Hank P. , Gold Stephen J. , Gonzalez‐Burgos Guillermo , Sved Alan F. , Tobe Ben J. , Wensel Theodore G. , Grace Anthony A.
Published: April 2008

Chronic stress exposure alters the central noradrenergic neurons originating from the locus coeruleus (LC). Previously, we demonstrated that evoked increases in the firing rate of LC neurons and their release of norepinephrine are enhanced following chronic cold exposure. In the present studies, we tested the hypothesis that reduced feedback inhibition of LC neurons might underlie these alterations in LC activity by examining the effect of α2‐autoreceptor stimulation on LC activity in chronically stressed rats usingin vivoandin vitrosingle unit recordings. Given that regulators of G‐protein signaling (RGS) proteins can impact the coupling of α2‐autoreceptors to downstream signaling cascades, we also explored the expression of several RGS proteins following chronic stress exposure. We observed that the α2‐autoreceptor‐evoked inhibition of LC neurons was reduced and that the expression of RGS7 was increased following chronic stress exposure. Finally, we demonstrated that intracellular administration of RGS7 via patch clamp electrodes mimicked the stress‐induced decrease in clonidine‐evoked autoreceptor‐mediated inhibition. These novel data provide a mechanism to explain how chronic stress‐induced alterations in receptor coupling can result in changes in α2‐autoreceptor control of noradrenergic function throughout the central nervous system, potentially leading to alterations in anxiety‐related behaviors, and may suggest novel therapeutic targets for the treatment of mood and anxiety disorders.
Expression and function of striatal enriched protein tyrosine phosphatase is profoundly altered in cerebral ischemia
Authors: Braithwaite Steven P. , Xu Jian , Leung John , Urfer Roman , Nikolich Karoly , Oksenberg Donna , Lombroso Paul J. , Shamloo Mehrdad
Published: April 2008

Striatal enriched protein tyrosine phosphatase (STEP) acts in the central nervous system to dephosphorylate a number of important proteins involved in synaptic function including ERK and NMDA receptor subunits. These proteins are also linked to stroke, in which cerebral ischemia triggers a complex cascade of events. Here we demonstrate that STEP is regulated at both the transcriptional and the post‐transcriptional levels in rat models of cerebral ischemia and that its regulation may play a role in the outcome of ischemic insults. After transient middle cerebral artery occlusion, there are profound decreases in the levels of STEP mRNA, whilst in global ischemia STEP mRNA is selectively down‐regulated in areas susceptible to ischemic damage. In a neuroprotective preconditioning paradigm, and in regions of the brain that are relatively resistant to ischemic damage, STEP mRNA levels are increased. Furthermore, there is a significant processing of STEP after ischemia to generate a novel species, STEP33, resulting in a redistribution of STEP from membrane‐bound to soluble compartments. Concomitant with the cleavage of mature forms of STEP, there are changes in the phosphorylation state of ERK. We show that the cleavage of STEP leads to a catalytically active form, but this cleaved form no longer binds to and dephosphorylates its substrate pERK. Therefore, in response to ischemic insults, there are profound reductions in both the amount and the activity of STEP, its localization, as well as the activity of one of its key substrates, pERK. These changes in STEP may reflect a critical role in the outcomes of ischemic brain injury.
A primitive social circuit: vasotocin–substance P interactions modulate social behavior through a peripheral feedback mechanism in goldfish
Authors: Thompson R. R. , Walton J. C. , Bhalla R. , George K. C. , Beth E. H.
Published: April 2008

At its core, the polyvagal theory proposes that peptides affect simple social behaviors through influences on hindbrain autonomic processes. To test this mechanism, we compared the effects of fore‐ and hindbrain infusions of vasotocin (VT) on social approach behavior in goldfish. VT infusions into the 4th ventricle, which ink infusions verified did not move rostrally to the forebrain, inhibited social approach at a lower dose than did infusions into the 3rd ventricle, which did diffuse to the hindbrain. Thus, VT actions in the hindbrain appear to modulate this simple social behavior. We then identified a population of substance P (SP)‐immunoreactive cells in the hindbrain that are encapsulated by putative VT terminals, and determined that those cells project to the periphery. Injecting SP peripherally, as with infusing VT centrally, inhibited social approach, and peripheral injections of an SP antagonist, but not central infusions, abolished the behavioral effects of central VT infusions. We therefore propose that VT inhibits social approach by activating SP cells in the hindbrain, which then induce changes in body state that feed back to the brain. Central VT infusions did not inhibit feeding, suggesting that this VT mechanism selectively affects appetitive social responses. Because VT projections to the hindbrain are highly conserved in vertebrates, influences on peripheral feedback processes like the one we have described in goldfish may reflect how VT affected simple social behaviors in ancestral vertebrates and thus preadapted members of this peptide family to play increasingly complex roles in social and emotional regulation in modern animals.
Neonatal stimulation of 5‐HT2receptors reduces androgen receptor expression in the rat anteroventral periventricular nucleus and sexually dimorphic preoptic area
Authors: Dakin C. L. , Wilson C. A. , Kalló I. , Coen C. W. , Davies D. C.
Published: April 2008

Masculinization of the brain is dependent upon a perinatal surge in testosterone. It also requires a transient decrease in hypothalamic 5‐HT concentration and turnover and an increase in androgen receptor (AR) expression during the second postnatal week. We have previously shown that increasing 5‐HT activity over this period in male or androgenized female rats feminizes their adult behaviour and also feminizes the size of their anteroventral periventricular nucleus (AVPV) and sexually dimorphic nucleus of the preoptic area (SDN‐POA). To investigate the role of 5‐HT in sexual differentiation of the brain, 5‐HT activity was raised over postnatal days 8–16 in male, female and androgenized female rats by daily administration of the 5‐HT2receptor agonist (–)[2,5 dimethoxy‐4‐iodophenyl]‐2‐amino propane hydrochloride [(–)DOI]. By postnatal day 18, the size of the AVPV and SDN‐POA was sexually dimorphic; their sizes were feminized by (–)DOI treatment. In the absence of (–)DOI treatment, there were significantly more AR‐immunoreactive cells in the AVPV of males, and in the SDN‐POA of males and androgenized females, than in those of females on postnatal day 18. (–)DOI treatment reduced the number of AR‐immunoreactive cells in the AVPV and SDN‐POA of males and androgenized females, but not of females, by postnatal day 18. These results suggest that 5‐HT2receptor activation can influence sexual differentiation of the brain by controlling AR expression.
Characterization of the vulnerability to repeated stress in Fischer 344 rats: possible involvement of microRNA‐mediated down‐regulation of the glucocorticoid receptor
Authors: Uchida Shusaku , Nishida Akira , Hara Kumiko , Kamemoto Toshiki , Suetsugi Masatomo , Fujimoto Michiko , Watanuki Toshio , Wakabayashi Yusuke , Otsuki Koji , McEwen Bruce S. , Watanabe Yoshifumi
Published: April 2008

In the present study, we established and characterized an animal model of vulnerability to repeated stress. We found that control Sprague–Dawley (SD) rats showed a gradual decrease in the HPA axis response following 14 days of repeated restraint stress, whereas Fischer 344 (F344) rats did not show such HPA axis habituation. Similar habituation was observed in the expression of c‐fos mRNA, corticotropin‐releasing hormone hnRNA, and phospho‐CREB and phospho‐ERK proteins in the hypothalamic paraventricular nucleus (PVN) of SD rats, but not in the F344 rats. In addition, repeatedly restrained F344 rats exhibited decreased cell proliferation in the dentate gyrus of the hippocampus and increased anxiety‐related behaviours, while repeatedly restrained SD rats exhibited a selective enhancement of hippocampal cell proliferation in the ventral area. Moreover, we found a lower expression of glucocorticoid receptor (GR) protein, but not mRNA, in the PVN of F344 rats compared to SD rats. We also identified that microRNA (miR)‐18a inhibited translation of GR mRNA in cultured neuronal cells and that increased expression of miR‐18a in the PVN was observed in F344 rats compared with SD rats. These strain differences in GR protein levels were not found in the hippocampus and prefrontal cortex, and the expression of miR‐18a was much lower in these brain regions than in the PVN. Our results suggest that F344 rats could be a useful animal model for studying vulnerability to repeated stress, and that miR‐18a‐mediated down‐regulation of GR translation may be an important factor to be considered in susceptibility to stress‐related disorders.
Paraplegia after thoracotomy under combined general and epidural anesthesia in a child
Authors: ALLISON C.E. , ARONSON D.C. , GEUKERS V.G.M. , VAN DEN BERG R. , SCHLACK W.S. , HOLLMANN M.W.
Published: April 2008

A 9‐year‐old boy underwent a thoracotomy for excision of his right third rib under combined general and epidural anesthesia for a Ewings sarcoma. Postoperatively, he was found to have a complete T2–3 paraplegia. Permanent paraplegia was described as a rare complication of thoracotomy in adults, and very rarely after epidural analgesia in adults and babies. This was the first report in a child.
Scaling of respiration to nitrogen in leaves, stems and roots of higher land plants
Authors: Reich Peter B. , Tjoelker Mark G. , Pregitzer Kurt S. , Wright Ian J. , Oleksyn Jacek , Machado Jose‐Luis
Published: April 2008

Using a database of 2510 measurements from 287 species, we assessed whether general relationships exist between mass‐based dark respiration rate and nitrogen concentration for stems and roots, and if they do, whether they are similar to those for leaves. The results demonstrate strong respiration–nitrogen scaling relationships for all observations and for data averaged by species; for roots, stems and leaves examined separately; and for life‐forms (woody, herbaceous plants) and phylogenetic groups (angiosperms, gymnosperms) considered separately. No consistent differences in the slopes of these log–log scaling relations were observed among organs or among plant groups, but respiration rates at any common nitrogen concentration were consistently lower on average in leaves than in stems or roots, indicating that organ‐specific relationships should be used in models that simulate respiration based on tissue nitrogen concentrations. The results demonstrate both common and divergent aspects of tissue‐level respiration–nitrogen scaling for leaves, stems and roots across higher land plants, which are important in their own right and for their utility in modelling carbon fluxes at local to global scales.
Coexistence through spatio‐temporal heterogeneity and species sorting in grassland plant communities
Authors: Questad Erin J. , Foster Bryan L.
Published: April 2008

The effect of spatial heterogeneity on species coexistence relies on the degree of niche heterogeneity in the habitat and the ability of species to exploit the available niche opportunities. We studied species coexistence in a perennial grassland, and tested whether small‐scale disturbances create environmental heterogeneity that affects coexistence and whether the functional diversity of species in the species pool affects the ability of community composition to reflect heterogeneity through species sorting. We manipulated the spatio‐temporal heterogeneity of disturbance and the functional diversity of species added as seed and measured their impact on the spatial turnover of species composition. Disturbance increased environmental heterogeneity and spatial turnover, and the effect of heterogeneity on turnover was greatest in the presence of a functionally diverse species pool, showing the importance of trait variation among species for exploiting environmental heterogeneity, and suggesting that coexistence occurred due to species sorting among heterogeneous niches.
A cross‐system synthesis of consumer and nutrient resource control on producer biomass
Authors: Gruner Daniel S. , Smith Jennifer E. , Seabloom Eric W. , Sandin Stuart A. , Ngai Jacqueline T. , Hillebrand Helmut , Harpole W. Stanley , Elser James J. , Cleland Elsa E. , Bracken Matthew E. S. , Borer Elizabeth T. , Bolker Benjamin M.
Published: April 2008

Nutrient availability and herbivory control the biomass of primary producer communities to varying degrees across ecosystems. Ecological theory, individual experiments in many different systems, and system‐specific quantitative reviews have suggested that (i) bottom–up control is pervasive but top–down control is more influential in aquatic habitats relative to terrestrial systems and (ii) bottom–up and top–down forces are interdependent, with statistical interactions that synergize or dampen relative influences on producer biomass. We used simple dynamic models to review ecological mechanisms that generate independent vs. interactive responses of community‐level biomass. We calibrated these mechanistic predictions with the metrics of factorial meta‐analysis and tested their prevalence across freshwater, marine and terrestrial ecosystems with a comprehensive meta‐analysis of 191 factorial manipulations of herbivores and nutrients. Our analysis showed that producer community biomass increased with fertilization across all systems, although increases were greatest in freshwater habitats. Herbivore removal generally increased producer biomass in both freshwater and marine systems, but effects were inconsistent on land. With the exception of marine temperate rocky reef systems that showed positive synergism of nutrient enrichment and herbivore removal, experimental studies showed limited support for statistical interactions between nutrient and herbivory treatments on producer biomass. Top–down control of herbivores, compensatory behaviour of multiple herbivore guilds, spatial and temporal heterogeneity of interactions, and herbivore‐mediated nutrient recycling may lower the probability of consistent interactive effects on producer biomass. Continuing studies should expand the temporal and spatial scales of experiments, particularly in understudied terrestrial systems; broaden factorial designs to manipulate independently multiple producer resources (e.g. nitrogen, phosphorus, light), multiple herbivore taxa or guilds (e.g. vertebrates and invertebrates) and multiple trophic levels; and – in addition to measuring producer biomass – assess the responses of species diversity, community composition and nutrient status.
Biodiversity of polycyclic aromatic hydrocarbon‐degrading bacteria from deep sea sediments of the Middle Atlantic Ridge
Authors: Cui Zhisong , Lai Qiliang , Dong Chunming , Shao Zongze
Published: April 2008

The bacteria involved in the biodegradation of polycyclic aromatic hydrocarbons (PAHs) in deep sea subsurface environments are largely unknown. In order to reveal their biodiversity, sediments from 2.2 m under the bottom surface at a water depth of 3542 m were sampled on the Middle Atlantic Ridge with a gravity column sampler. The sediments were promptly enriched with either crude oil or a mixture of PAHs (naphthalene, phenanthrene and pyrene) as the sole carbon source, and further enriched with the PAH mixture mentioned above in the lab. The resulting consortia were named C2CO and C2PPN respectively. Their bacterial composition was analysed with plate cultivation, PCR‐DGGE and 16S rDNA library analysis. On plates, isolates belonging to Pseudoalteromonas, Halomonas, Marinobacter, Thalassospira and Tistrella dominated the culturable populations. With PCR‐DGGE, five major bands closely related to Cycloclasticus, Alteromonas, Thalassospira, Alcanivorax and Rhodospirillaceae were detected in consortium C2CO, while only one major band of Cycloclasticus was detected in consortium C2PPN. In addition, the dynamics of community structure in response to aromatic substrate alterations were examined. As a result, three ribotypes of Cycloclasticus were detected by 16S rDNA library analysis, one which played a key role in phenanthrene degradation; two Alteromonas bacteria dominated the naphthalene reselected consortium. Although bacteria of the two genera grew as the main members of the communities, none of them were isolated, probably owing to their poor cultivability. These results confirm that bacteria of Cycloclasticus are important obligate PAH degraders in marine environments, and coexist with other degrading bacteria that inhabit the deep subsurface sediment of the Atlantic. This supports the view that PAH accumulation and bioattenuation occur in remote areas consistently and continuously.
Clinical and epidemiological features of patients with genitourinary tract tumour in a blackfoot disease endemic area of Taiwan
Authors: Tan Lia‐Beng , Chen Kow‐Tong , Guo How‐Ran
Published: April 2008

OBJECTIVES

To evaluate the clinical and epidemiological characteristics of patients with genitourinary (GU) tract transitional cell carcinoma (TCC) in an endemic area of blackfoot disease (BFD), the arsenic‐exposed group, to compare them with characteristics among other non‐BFD endemic areas (unexposed group).

PATIENTS AND METHODS

In all, 474 patients with pathologically diagnosed GU‐TCC were enrolled in the study. All follow‐up data were prospectively collected and entered into a database throughout the study period. Statistical analysis was used to determine the association between clinical variables and prognosis, and multivariate regression models were used to assess the association between arseniasis and mortality from GU‐TCC.

RESULTS

There were no significant differences between the groups in age, sex, tumour stage and grade. However, the exposed group had a significantly higher proportion of females. The overall 5‐year survival rate of patients with upper urinary tract (UUT) TCC was 49%, and the two groups had similar 5‐year survival rates. The overall 5‐year survival rate of patients with urinary bladder (UB) TCC was 68.3%, and there was a statistically significant difference in survival between the groups, with a 5‐year survival rate of 58.7% for the exposed and 72.4% for the unexposed group. For patients with early‐stage (pTa and pT1) UB cancers, the death rate was five times higher in exposed patients with tumour progression and recurrence after transurethral resection of bladder tumour than in the unexposed group.

CONCLUSIONS

There was a significantly higher mortality rate for UB‐TCC among exposed patients in the area endemic for arseniasis than in those from other non‐endemic areas. The arsenic content of artesian‐well water might contribute to the increased ratio of female patients with GU‐TCC and the unusually high incidence of UUT‐TCC in the BFD endemic area in Taiwan.
Road traffic accidents and diabetes: insulin use does not determine risk
Authors: Lonnen K. F. , Powell R. J. , Taylor D. , Shore A. C. , MacLeod K. M.
Published: April 2008

Aims  Progressive restrictions placed on insulin‐treated patients with diabetes exclude them from driving group 2 and class C1 and D1 vehicles. This reflects an assumption that an increased risk of hypoglycaemia in these patients will cause road traffic accidents. These restrictions have been implemented without any consistent evidence that this is the case. The aim of the study was therefore to investigate whether the rate of road traffic collisions in insulin‐treated patients was higher than that of the non‐diabetic population using a population register‐based study.

Methods  A historical cohort study combined information from the Devon and Cornwall Constabulary database on road traffic collisions with the district wide retinal screening database, to provide an anonymized matched database of road traffic collisions in the diabetic population. Accident rates were calculated in the diabetic population and compared to rates in the non‐diabetic population using relative risks.

Results  The estimated overall annual accident rate for the non‐diabetic population was 1469 per 100 000 vs. 856 per 100 000 for the diabetic population as a whole (Chi‐squared, P < 0.001). On stratification of the groups by age, within the insulin‐treated group there was no significant difference in the accident rate compared to the non‐diabetic population, with relative risks between 0.51 [confidence interval (CI) 0.25–1.05] and 1.13 (CI 0.88–1.46).

Conclusions  Our findings suggest that insulin‐treated patients as a group do not pose an increased risk to road safety. They reiterate the need for an individualized risk‐based assessment when considering driving restrictions.
Impact of 3‐year lifestyle intervention on postprandial glucose metabolism: the SLIM study
Authors: Roumen C. , Corpeleijn E. , Feskens E. J. M. , Mensink M. , Saris W. H. M. , Blaak E. E.
Published: April 2008

Objective  To determine the effect of a 3‐year diet and exercise lifestyle intervention, based on general public health recommendations, on glucose tolerance, insulin resistance and metabolic cardiovascular risk factors in Dutch subjects with impaired glucose tolerance (IGT).

Methods  The study was a randomized controlled lifestyle intervention over 3 years. A total of 147 IGT subjects (75 male, 72 female) were randomized to the intervention (INT) group or control (CON) group; 106 subjects (52 INT, 54 CON) completed 3 years of intervention. Annually, glucose, insulin and free fatty acid (FFA) concentrations were determined fasting and after an oral glucose tolerance test. Measurements of body weight, serum lipids, blood pressure and maximal aerobic capacity were also performed.

Results  Analysis of those who completed the 3‐year trial, showed that the lifestyle intervention improved body weight (INT −1.08 ± 4.30 kg; CON +0.16 ± 4.91 kg, P = 0.01), homeostatis model assessment index for insulin resistance and 2‐h FFA. Two‐hour glucose concentrations improved in the INT group, the difference being most pronounced after 1 year, with a return to baseline values after 3 years, from 8.59 ± 1.55 to 8.55 ± 0.34 mm; in contrast, 2‐h glucose deteriorated in the CON group—from 8.46 ± 1.84 to 9.35 ± 2.50 mm (P = 0.02). In the INT group, diabetes incidence was reduced by 58% (P = 0.025).

Conclusion  Our lifestyle intervention showed a sustained beneficial effect on 2‐h glucose concentrations, insulin resistance and 2‐h FFA, even after 3 years. Our lifestyle intervention is effective, but for implementation more information is needed about factors influencing adherence.
Insulin and glucose profiles during continuous subcutaneous insulin infusion compared with injection of a long‐acting insulin in Type 2 diabetes1
Authors: Parkner T. , Laursen T. , Vestergaard E. T. , Hartvig H. , Smedegaard J. S. , Lauritzen T. , Christiansen J. S.
Published: April 2008

Aims  To compare insulin and glucose profiles during basal continuous subcutaneous infusion of a rapid‐acting insulin analogue and once daily subcutaneous injection of a long‐acting insulin analogue in Type 2 diabetes.

Methods  Twenty‐one patients with Type 2 diabetes treated with oral glucose‐lowering agents were randomized in this two‐period crossover study to an equivalent 24‐h dose of continuous subcutaneous infusion of insulin aspart and subsequently once‐daily bedtime subcutaneous injection of insulin glargine, or vice versa, for eight consecutive days. Plasma profiles of insulin and glucose were recorded.

Results  On the last day of each treatment period, the area under the curve (AUC) for glucose was 10% lower on the continuous subcutaneous infusion regimen compared with the insulin injection regimen (P = 0.002). This was accomplished by a flat exogenous insulin infusion profile compared with a peaking profile with injected insulin (AUC was 74% higher after injection compared with pre‐injection levels (P = 0.001)). During the last 6 days in each treatment period, the intra‐subject variability of exogenous fasting insulin levels in the mornings was 41% lower during insulin infusion compared with insulin injection (P = 0.012). The corresponding intra‐subject variability for fasting glucose only showed a tendency to be lower during infusion as compared to the injection regimen (28%; P = 0.104). Thirteen symptomatic‐only or minor hypoglycaemic episodes were recorded during the entire infusion period compared with three episodes during the injection period.

Conclusions  Basal continuous subcutaneous infusion of a rapid‐acting insulin analogue improved plasma insulin (more flat insulin profile with a lower variability) and glucose (lower AUC) profiles compared with once‐daily subcutaneous injection of a long‐acting insulin analogue in Type 2 diabetes.
Service quality for Type 2 diabetes in Australia: the patient perspective
Authors: Tabrizi J. S. , O’Rourke P. K. , Wilson A. J. , Coyne E. T.
Published: April 2008

Aims  To assess the service quality of care as perceived by people with Type 2 diabetes mellitus.

Methods  A cross‐sectional survey using a self‐administered questionnaire was carried out among members of Diabetes Australia–Queensland with Type 2 diabetes. For 12 aspects of service quality derived from a literature review and focus group research, patients scored the relative importance of the aspects and their perception of quality of received care. A measure of service quality was derived by combining the relative importance and actual performance.

Results  A total of 603people with Type 2 diabetes participated. Of the 12 aspects of care, communication, availability of support group, safety and prevention had the highest scores for importance; support group and basic amenities had the highest average performance values; but the highest service quality values were for support group, basic amenities, dignity and confidentiality. Younger participants had lower service quality scores (P = 0.001) and participants with good control of their diabetes had higher scores (P < 0.001). Compared with the reference population, our sample had 8.7% fewer people under 65 years old.

Conclusions  From the perspective of people with Type 2 diabetes, there is a notable gap between their expectations and what they have actually received in most aspects of provided care. In addition, overall service quality and six aspects of service quality (choice of care provider, accessibility, prevention, continuity, timeliness and safety) were identified to be of inadequate quality. Hence, this study demonstrates a significant opportunity to improve quality of healthcare services.
An effective system of nurse‐led diabetes care in rural Africa
Authors: Gill G. V. , Price C. , Shandu D. , Dedicoat M. , Wilkinson D.
Published: April 2008

Aims  Delivering adequate diabetes care is difficult in rural Africa because of drug and equipment shortages; as well as lack of trained medical expertise. We aimed to set up and evaluate a nurse‐led protocol and education‐based system in rural Kwazulu Natal in South Africa.

Methods  A treatment algorithm and education system adapted from previously validated methods was used; care was devolved to primary health clinics and was delivered by two nurses. Glycaemic control was assessed by glycated haemoglobin (HbA1c), assayed off site and not available for clinical use during the study.

Results  A total of 284 patients were enrolled, with 197 followed for 18 months (13 died and 26% lapsed during the period). HbA1c was 11.6 ± 4.5% (sd) at baseline, 8.7 ± 2.3% at 6 months and 7.7 ± 2.0% at 18 months. There was a small associated increase in weight but no increase in hypoglycaemia. Subgroup analysis showed that education alone, without drug type or dose changes, also improved control (HbA1c 10.6 ± 4.2% baseline and 7.6 ± 2.3% at 18 months). The service was very popular with patients, families and other health workers.

Conclusions  We conclude that a simple protocol and education‐based diabetes care system can be successfully introduced and run by nurses in rural Africa. Medium‐term glycaemic improvements are excellent and the service has been very well received.
The high prevalence of unrecognized anaemia in patients with diabetes and chronic kidney disease: a population‐based study
Authors: New J. P. , Aung T. , Baker P. G. , Yongsheng G. , Pylypczuk R. , Houghton J. , Rudenski A. , New R. P. , Hegarty J. , Gibson J. M. , O'Donoghue D. J. , Buchan I. E.
Published: April 2008

Background  Anaemia occurs early in the course of diabetes‐related chronic kidney disease (CKD). There is little evidence about the prevalence of anaemia in people with diabetes. The aim of this study was to assess the prevalence of anaemia, by stage of CKD, in the general diabetic population.

Methods  Haemoglobin (Hb) was measured on all glycated haemoglobin (HbA1c) samples and the most recent (< 4 months) estimated glomerular filtration rate (eGFR) was obtained. Anaemia (at treatment level) was defined as Hb < 110 g/l or the use of erythropoetic stimulating agents (ESA).

Results  Twelve per cent (10–14%) of people had Hb < 110 g/l. The prevalence of anaemia increased progressively with worsening CKD. People with CKD stage 3 accounted for the largest number of people with anaemia; 18% (95% CI 13–24%) had Hb < 110 g/l. Those with eGFR < 60 ml/min/1.73 m2 and not on ESA or dialysis were four (2–7) times more likely than patients with better renal function to have Hb < 110 g/l. The relation between Hb and eGFR became approximately linear below an eGFR of 83 ml/min/1.73 m2, where, for every 1 ml/min/1.73 m2 fall in eGFR, there was a 0.4 (0.3–0.5) g/l fall in haemoglobin.

Conclusions  This study demonstrates that anaemia, at levels where treatment is indicated, occurs commonly in people with diabetes and CKD stage 3 or worse. The screening for anaemia in current diabetes management should be extended.
Comparison of effects of combined ACE inhibitor and low‐dose thiazide diuretic with ACE inhibitor alone on insulin action in patients with hypertension and Type 2 diabetes: a double‐blind crossover study
Authors: McLaughlin D. M. , Atkinson A. B. , Ennis C. N. , Browne J. , Hunter S. J. , Sheridan B. , Bell P. M.
Published: April 2008

Aims  To establish the safety in terms of insulin sensitivity of a low dose thiazide/ACE inhibitor combination.

Methods  We examined the effects on insulin sensitivity of captopril either alone or in combination with low‐dose bendroflumethiazide (1.25 mg) in 15 hypertensive Type 2 diabetic patients. Insulin action was assessed using an isoglycaemic hyperinsulinaemic clamp in a double‐blind, randomised, crossover study after a 6‐week placebo run‐in and following two 12‐week treatment periods with captopril (C) (100 mg) alone or in combination with bendroflumethiazide (CB) (1.25 mg).

Results  Blood pressure was lower following CB compare to C (138/83 vs. 144/85 mmHg; P < 0.05) and both were lower than baseline (153/92 mmHg; P < 0.01). CB resulted in a significant increase in fasting plasma glucose compared to C (9.6 ± 2.6 vs. 8.5 ± 1.6 mmol/l; P < 0.05). Exogenous glucose infusion rates required to maintain isoglycaemia during hyperinsulinaemia were lower after CB compared to C (25.1 ± 13.3 vs. 34.2 ± 16.8 µmol/kg/min; P < 0.01) as were isotopically determined glucose utilisation rates (29.0 ± 12.4 vs. 36.6 ± 17.3 µmol/kg/min; P < 0.05). There was no significant difference in fasting endogenous glucose production between treatments (CB 9.3 ± 3.3 vs. C 8.6 ± 1.6 µmol/kg/min), nor between suppression following insulin (CB 4.0 ± 2.1 vs. C 4.3 ± 3.1 µmol/kg/min).

Conclusions  Combination of low‐dose bendroflumethiazide with captopril lowered blood pressure but resulted in deleterious effects on insulin action compared to captopril alone.
Production of cecropin A in transgenic rice plants has an impact on host gene expression
Authors: Campo Sonia , Manrique Silvia , García‐Martínez José , San Segundo Blanca
Published: April 2008

Expression of the cecropin A gene in rice confers resistance to the rice blast fungus Magnaporthe oryzae. In this study, a polymerase chain reaction‐based suppression subtractive hybridization approach was used to generate a cDNA macroarray from the elite japonica rice (Oryza sativa L.) cultivar ‘Senia’. Gene expression studies revealed that the expression of components of the protein secretory and vesicular transport machinery is co‐ordinately activated at the pre‐invasive stage of infection of rice by the blast fungus. Comparisons of gene expression between wild‐type and cecropin A plants revealed the over‐expression of genes involved in protection against oxidative stress in transgenic plants in the absence of the pathogen, which correlated well with the tolerance of these plants to oxidative stress. A subcellular fractionation analysis suggested that cecropin A accumulates in the endoplasmic reticulum in cecropin A rice. Moreover, a large number of genes related to the processes of synthesis, folding and stabilization of proteins that enter into the secretory pathway are over‐expressed in cecropin A rice, confirming that these plants constitutively express the unfolded protein response. Transgenic expression of cecropin A in rice has an effect on the transcriptional reprogramming that accompanies plant adaptation to fungal infection. Overall, this study provides evidence for transgene‐induced changes in gene expression in cecropin A rice under both optimal growth conditions and stress conditions imposed by fungal infection. The data also indicate that resistance to blast in cecropin A rice may be the consequence of a combination of the antifungal activity of cecropin A and cecropin A‐mediated over‐expression of rice genes.
FREE RIDERS AND PIOUS SONS – WHY SCIENCE RESEARCH REMAINS OBLIGATORY
Authors: CHAN SARAH , HARRIS JOHN
Published: April 2008

John Harris has previously proposed that there is a moral duty to participate in scientific research. This concept has recently been challenged by Iain Brassington, who asserts that the principles cited by Harris in support of the duty to research fail to establish its existence. In this paper we address these criticisms and provide new arguments for the existence of a moral obligation to research participation. This obligation, we argue, arises from two separate but related principles. The principle of fairness obliges us to support the social institutions which sustain us, of which research is one; while the principle of beneficence, or the duty of rescue, imposes upon us a duty to prevent harm to others, including by supporting potentially beneficial, even life‐saving research. We argue that both these lines of argument support the duty to research, and explore further aspects of this duty, such as to whom it is owed and how it might be discharged.
WHY WE ARE NOT MORALLY REQUIRED TO SELECT THE BEST CHILDREN: A RESPONSE TO SAVULESCU
Authors: STOLLER SARAH E.
Published: April 2008

The purpose of this paper is to review critically Julian Savulescu's principle of ‘Procreative Beneficence,’ which holds that prospective parents are morally obligated to select, of the possible children they could have, those with the greatest chance of leading the best life. According to this principle, prospective parents are obliged to use the technique of pre‐implantation genetic diagnosis (PGD) to select for the ‘best’ embryos, a decision that ought to be made based on the presence or absence of both disease traits and non‐disease traits such as intelligence. While several articles have been written in response to Savulescu's principle, none has systematically explored its philosophical underpinnings to demonstrate where it breaks down. In this paper I argue that the examples that Savulescu employs to support his theory in fact fail to justify it. He presents these examples as analogous to PGD, when in fact they differ from it in subtle but morally relevant ways. Specifically, Savulescu fails to acknowledge the fact that his examples evoke deontological and virtue ethics concerns that are absent in the context of PGD. These differences turn out to be crucial, so that, in the end, the analogies bear little support for his theory. Finally, I lay out the implications of this analysis for reproductive ethics.
IS THE NAIRU THEORY A MONETARIST, NEW KEYNESIAN, POST KEYNESIAN OR A MARXIST THEORY?
Authors: Stockhammer Engelbert
Published: April 2008

The NAIRU (non‐accelerating inflation rate of unemployment) theory has become the mainstream theory in explaining unemployment in Europe and is often used to justify demands for a cutback of the welfare state, such as reducing unemployment benefits. Close inspection reveals that it, perhaps surprisingly, shares some arguments with Post Keynesian and even Marxist theory. The paper proposes an underdetermined, encompassing NAIRU model, which is consistent with several theoretical traditions. Depending on the closure with respect to demand formation and determination of the NAIRU itself, the model allows for New Keynesian, Post Keynesian and Marxist results.
Targeting of nucleus‐encoded proteins to chloroplasts in plants
Authors: Jarvis Paul
Published: April 2008

Most chloroplast proteins are encoded in the nucleus and synthesized on free, cytosolic ribosomes in precursor form. Each precursor has an amino‐terminal extension called a transit peptide, which directs the protein through a post‐translational targeting pathway and is removed upon arrival inside the organelle. This ‘protein import’ process is mediated by the coordinate action of two multiprotein complexes, one in each of the envelope membranes: the TOC and TIC (Translocon at theOuter/Inner envelope membrane ofChloroplasts) machines. Many components of these complexes have been identified biochemically in pea; these include transit peptide receptors, channel proteins, and molecular chaperones. Intriguingly, theArabidopsisgenome encodes multiple, homologous genes for receptor components of the TOC complex. Careful analysis indicated that the different receptor isoforms operate in different import pathways with distinct precursor recognition specificities. These ‘substrate‐specific’ import pathways might play a role in the differentiation of different plastid types, and/or act to prevent deleterious competition effects between abundant and nonabundant precursors. Until recently, all proteins destined for internal chloroplast compartments were thought to possess a cleavable transit peptide, and to engage the TOC/TIC machinery. New studies using proteomics and other approaches have revealed that this is far from true. Remarkably, a significant number of chloroplast proteins are transported via a pathway that involves the endoplasmic reticulum and Golgi apparatus. Other recent reports have elucidated an intriguing array of protein targeting routes leading to the envelope membranes themselves.

ContentsSummary257I.Introduction258II.Targeting signals260III.Envelope translocation by the TOC/TIC pathway262IV.Early stages of the TOC/TIC pathway263V.Later stages of the TOC/TIC pathway272VI.Targeting to the envelope system274VII.Alternative or ‘noncanonical’ import pathways276VIII.Conclusion and future perspectives278Acknowledgements278References278
Transnational Agrarian Movements: Origins and Politics, Campaigns and Impact
Authors: BORRAS JR SATURNINO M. , EDELMAN MARC , KAY CRISTÓBAL
Published: April 2008

This essay introduces a special issue of theJournal of Agrarian Changeon transnational agrarian movements (TAMs). The contributors’ methods and subjects vary widely in geographical, temporal and political scope. The contributors to this collection share an understanding of TAMs’ complexity that grows out of an appreciation of the complicated historical origins and the delicate political balancing acts that necessarily characterize any effort to construct cross‐border alliances linking highly heterogeneous organizations, social classes, ethnicities, political viewpoints and regions. This introductory essay outlines the TAMs’ deep historical roots and also explains why and how the authors in this collection see this complexity as an essential element in understanding TAMs. This complexity can be understood by looking at seven common themes: (i) representation and agendas, (ii) political strategies and forms of actions, (iii) impact, (iv) TAMs as arenas of action between different (sub)national movements, (v) class origins, (vi) ideological and political differences and (vii) the dynamics of alliance‐building. By acknowledging TAMs’ contradictions, ambiguities and internal tensions, the authors also seek, from the standpoint of engaged intellectuals, to advance a transformative political project by better comprehending its origins, past successes and failures, and current and future challenges.
Peasants Make Their Own History, But Not Just as They Please . . .
Authors: MCMICHAEL PHILIP
Published: April 2008

This essay employs contemporary peasant mobilizing discourses and practices to evaluate the terms in which we understand agrarian movements today, through an exercise of historical specification. First, it considers why the terms of the original agrarian question no longer apply to agrarian change today. The shift in the terms corresponds to the movement from the late‐nineteenth century and twentieth century, when states were the organizing principle of political‐economy, to the twenty‐first century, when capital has become the organizing principle. Second, and related, agrarian mobilizations are viewed here as barometers of contemporary political‐economic relations. In politicizing the socio‐ecological crisis of neoliberalism, they problematize extant categories of political and sociological analysis, re‐centring agriculture and food as key to democratic and sustainable relations of social production.
La Vía Campesina and its Global Campaign for Agrarian Reform
Authors: BORRAS JR SATURNINO M.
Published: April 2008

Vía Campesina's ‘Global Campaign for Agrarian Reform’ (GCAR) has made a significant impact (inter)nationally in reshaping the terms of the land reform debates. However, its impact on other land policy dynamics has been marginal. Meanwhile, the campaign inadvertently exposed latent class‐based and ideological distinctions within the transnational network. This essay explains how the GCAR emerged, and has been able to influence the broader global land reform debates, but has not been able (so far) to significantly impact other major dimensions of the land policy debates. It argues that if GCAR is to retain relevance, it must deepen and broaden its current position on land to go beyond the parameters of conventional land reform. Moreover, it must also find ways to better integrate ‘global issue framing from above’ with ‘local/national campaigns from below’ if it is to strengthen its process of ‘issue/campaign externalization/transnationalization’. Doing this may require the network to rethink some of its well‐established organizational practices and ideological perspectives.
Mobilizing Against GM Crops in India, South Africa and Brazil
Authors: SCOONES IAN
Published: April 2008

This paper explores the national and transnational character of mobilization against GM crops in India, South Africa and Brazil in the ten‐year period to 2005. By examining the contexts and practices of mobilization across the three countries, and in particular the complex, often fraught, local and global connections, the paper examines the diverse mobilizations that have occurred. The paper argues that to understand these processes, particular national political and economic contexts must be appreciated, alongside how the GM debates articulate with other foci for activism and the complex and often fragile nature of alliances that make up activist networks. The paper shows how the debate about GM crops has become a much wider one: about the future of agriculture and small‐scale farmers, about corporate control and property rights and about the rules of global trade. In sum, a debate not just about the pros and cons of a particular set of technologies, but about politics and values and the future of agrarian society.
Whose Rules Rule? Contested Projects to Certify ‘Local Production for Distant Consumers’1
Authors: FRIEDMANN HARRIET , MCNAIR AMBER
Published: April 2008

As transnational agrifood supply chains undermine local markets and agroecosystems, farmers everywhere must adapt or find alternative connections to customers. Two projects for global agrifood relations are emerging: from above, led by supermarkets, which enforces standard norms; and an alternative from below, presently led by the Slow Food Foundation for Biodiversity, which qualifies products specific to diverse cultural/natural regions. We consider two examples of regional certification: the Cojote Rojo ecolabel which arose in the context of recent expansion of export avocado production in the highlands of Michoacán, Mexico; and Local Food Plus, a regional label designed to promote public institutional purchases as a route to get regional products into markets in Ontario, Canada. We suggest that many experiments in re‐embedding agriculture are emerging in interstices of the dominant system in both North and South. These agrarian social movements are less visible than resistance movements and anticipate a possible future based on global interconnections among diverse farming systems embedded in their cultural and natural contexts.