bluuebunny/crossref_metadata_2025_split huggingface dataset:
Approaches to the identification of susceptibility genes
Authors: COLLINS A. 
Published: November 2008

SUMMARY Although previous studies have revealed a great deal about the genetic basis of susceptibility and resistance to parasite infection, there is now an opportunity to considerably enhance understanding through genome‐wide association mapping. The application of association mapping to complex inheritance has recently become achievable given reduced costs, sophisticated genotyping platforms and powerful statistical methods which build upon increased knowledge of the linkage disequilibrium structure of the human genome. Linkage mapping and related approaches remain useful for the localization of the rarer genetic variants and candidate region association studies can be a very cost‐effective route to progress. However, genome‐wide association offers the greatest promise, despite the challenges posed by phenotype complexity, ensuring genotype coverage/quality and robust statistical analysis. The available approaches for mapping genes underlying susceptibility are reviewed here, emphasizing their relative merits and drawbacks and highlighting specific software tools and resources that enable successful mapping.
Comparative analysis of leaf‐type ferredoxin‐NADP+ oxidoreductase isoforms in Arabidopsis thaliana
Authors: Lintala Minna , Allahverdiyeva Yagut , Kangasjärvi Saijaliisa , Lehtimäki Nina , Keränen Mika , Rintamäki Eevi , Aro Eva‐Mari , Mulo Paula 
Published: November 2008

SummaryPhysiological roles of the two distinct chloroplast‐targeted ferredoxin‐NADP+ oxidoreductase (FNR) isoforms in Arabidopsis thaliana were studied using T‐DNA insertion line fnr1 and RNAi line fnr2. In fnr2 FNR1 was present both as a thylakoid membrane‐bound form and as a soluble protein, whereas in fnr1 the FNR2 protein existed solely in soluble form in the stroma. The fnr2 plants resembled fnr1 in having downregulated photosynthetic properties, expressed as low chlorophyll content, low accumulation of photosynthetic thylakoid proteins and reduced carbon fixation rate when compared with wild type (WT). Under standard growth conditions the level of F0‘rise’ and the amplitude of the thermoluminescence afterglow (AG) band, shown to correlate with cyclic electron transfer (CET), were reduced in both fnr mutants. In contrast, when plants were grown under low temperatures, both fnr mutants showed an enhanced rate of CET when compared with the WT. These data exclude the possibility that distinct FNR isoforms feed electrons to specific CET pathways. Nevertheless, the fnr2 mutants had a distinct phenotype upon growth at low temperature. The fnr2 plants grown at low temperature were more tolerant against methyl viologen (MV)‐induced cell death than fnr1 and WT. The unique tolerance of fnr2 plants grown at low temperature to oxidative stress correlated with an increased level of reduced ascorbate and reactive oxygen species (ROS) scavenging enzymes, as well as with a scarcity in the accumulation of thylakoid membrane protein complexes, as compared with fnr1 and WT. These results emphasize a critical role for FNR2 in the redistribution of electrons to various reducing pathways, upon conditions that modify the photosynthetic capacity of the plant.
MTP1‐dependent Zn sequestration into shoot vacuoles suggests dual roles in Zn tolerance and accumulation in Zn‐hyperaccumulating plants
Authors: Gustin Jeffery L. , Loureiro Marcello E. , Kim Donggiun , Na Gunnam , Tikhonova Marina , Salt David E. 
Published: November 2008

SummaryThe integral membrane protein Thlaspi goesingense metal tolerance protein 1 (TgMTP1) has been suggested to play an important role in Zn hyperaccumulation in T. goesingense. Here, we show that the TgMTP1 protein is accumulated to high levels at the vacuolar membrane in shoot tissue of T. goesingense. TgMTP1 is likely to act in the transport of Zn into the vacuole, enhancing both Zn accumulation and tolerance. By specifically expressing TgMTP1 in Arabidopsis thaliana shoots, we show that TgMTP1, localized at the vacuolar membrane, can drive the enhanced shoot accumulation of Zn by initiating a systemic Zn deficiency response. The systematic response includes increased expression of Zn transporters (ZIP3, ZIP4, ZIP5 and ZIP9) in both shoot and root tissue. Furthermore, shoot‐specific accumulation of TgMTP1 at the vacuolar membrane also leads to increased resistance to Zn in A. thaliana, probably through enhanced Zn compartmentalization in the vacuole. Such evidence leads to the conclusion that the high levels of TgMTP1 at the vacuolar membrane in shoot tissue of the Zn hyperaccumulator T. goesingense play a role in both Zn tolerance and enhanced Zn uptake and accumulation, via the activation of a systemic Zn deficiency response.
Nitric oxide modulates ozone‐induced cell death, hormone biosynthesis and gene expression in Arabidopsis thaliana
Authors: Ahlfors Reetta , Brosché Mikael , Kollist Hannes , Kangasjärvi Jaakko 
Published: November 2008

SummaryNitric oxide (NO) is involved together with reactive oxygen species (ROS) in the activation of various stress responses in plants. We have used ozone (O3) as a tool to elicit ROS‐activated stress responses, and to activate cell death in plant leaves. Here, we have investigated the roles and interactions of ROS and NO in the induction and regulation of O3‐induced cell death. Treatment with O3 induced a rapid accumulation of NO, which started from guard cells, spread to adjacent epidermal cells and eventually moved to mesophyll cells. During the later time points, NO production coincided with the formation of hypersensitive response (HR)‐like lesions. The NO donor sodium nitroprusside (SNP) and O3 individually induced a large set of defence‐related genes; however, in a combined treatment SNP attenuated the O3 induction of salicylic acid (SA) biosynthesis and other defence‐related genes. Consistent with this, SNP treatment also decreased O3‐induced SA accumulation. The O3‐sensitive mutant rcd1 was found to be an NO overproducer; in contrast, Atnoa1/rif1 (Arabidopsis nitric oxide associated 1/resistant to inhibition by FSM1), a mutant with decreased production of NO, was also O3 sensitive. This, together with experiments combining O3 and the NO donor SNP suggested that NO can modify signalling, hormone biosynthesis and gene expression in plants during O3 exposure, and that a functional NO production is needed for a proper O3 response. In summary, NO is an important signalling molecule in the response to O3.
Reproduction of an early‐flowering Mediterranean mountain narrow endemic (Armeria caespitosa) in a contracting mountain island
Authors: García‐Camacho R. , Escudero A. 
Published: November 2008

AbstractReproduction at population lower edges is important for plant species persistence, especially in populations on contracting high‐mountain islands. In this context, the ability of plants to reproduce in different microhabitats seems to be important to guarantee seed production in stressful environments, such as Mediterranean high mountains. We hypothesised that the warmer and drier conditions at the lower edge would be deleterious for the reproduction of Armeria caespitosa, an early‐flowering plant. In addition, reproductive plasticity along this mountain gradient may also be microhabitat‐dependent. We studied factors affecting the reproductive success of A. caespitosa, an endemic of the Spanish Sistema Central. We considered a complex set of predictors, including phenology, plant size and environmental factors at different scales using generalised estimating equations and generalised linear models. Microhabitat, together with the position in the altitudinal gradient and inter‐annual variability affected the reproduction of A. caespitosa. In addition, individuals with longer flowering periods (duration of flowering) had significantly lower fruit set and a higher number of unviable seeds; delayed flowering peaks favoured the production of both viable and unviable fruits. Microhabitat variability over an altitudinal range is relevant for the reproduction of A. caespitosa, and is more important at the lower edge of the altitudinal range, where the species faces the most adverse conditions. In addition, the ability to reproduce in different microhabitats might increase the chances of the species to cope with environmental uncertainties under on‐going climate warming. Finally, reproduction of this early‐flowering plant is constrained by summer drought, which might shape its reproductive phenology.
Folliculogenesis and Morphometry of Oocyte and Follicle Growth in the Feline Ovary
Authors: Reynaud K , Gicquel C , Thoumire S , Chebrout M , Ficheux C , Bestandji M , Chastant‐Maillard S 
Published: November 2008

ContentsThis study was designed to describe, both quantitatively (morphometry) and qualitatively (histological differentiation), follicle and oocyte growth in the feline ovary. The ovaries of 43 cats were collected and processed for histology. The diameters of 832 follicle/oocyte pairs were measured, with and without zona pellucida (ZP), and a special emphasis was placed on the study of early folliculogenesis. Primordial, primary, secondary, pre‐antral and early antral follicles were measured at 44.3, 86.2, 126.0, 155.6 and 223.8 μm in diameter respectively. A biphasic pattern of follicle and oocyte growth was observed. Before antrum formation, follicle (x) and oocyte (y) size were positively and linearly correlated (y = 0.500x + 20.01, r2 = 0.89). Antrum formation occurred when the follicle reached 160–200 μm in diameter (when oocyte was at 102 μm). After antrum formation, a decoupling was observed, a minimal increase in oocyte size contrasting with a significant follicle development (y = 0.001x + 114.39, r2 = 0.01). The pre‐ovulatory follicle diameter was approximately 3500 μm and the maximal oocyte diameter was 115 μm. The ZP, absent in primordial and primary follicles, appeared at the secondary stage and reached almost 6 μm at the pre‐ovulatory stage. These results suggest that (i) in feline ovary, follicle and oocyte growth pattern is similar to that observed in other mammals; (ii) the antrum forms in 160–200 μm follicles, which represents 5% of the pre‐ovulatory diameter and (iii) the oocyte had achieved more than 90% of its maximal growth at the stage of antrum formation.
Technical Aspects of Laparoscopic Ovarian Autograft in Ewes After Cryopreservation by Slow‐Cooling Protocol
Authors: Massardier J , Courbiere B , Lornage J , Mazoyer C , Poirel MT , Martinot S , Franck M , Salle B 
Published: November 2008

ContentsIatrogenic ovarian failure and infertility are long term‐term side effects of anticancerous gonadotoxic treatments in children or women of reproductive year. Ovarian cortex cryopreservation can be a solution to preserve immature germinal cells before gonadotoxic treatment, for later transplantation. The aim of our study was to prove the efficiency of a laparoscopic technique for orthotopic graft after a slow‐freezing/thawing protocol, and to evaluate the effect of ovarian cryopreservation and autograft on the primordial follicle survival rate. Experimental surgical study was performed on 6‐ to 12‐month‐old ewes. The study was approved by the ethic committee of the Lyon‐veterinary‐school. The left ovary was removed by laparoscopy and cut in half, and medulla was excised. In group 1 (n = 6), autograft was performed immediately on the right ovary, and in group 2 (n = 6), graft was performed after a slow‐freezing/thawing protocol. The second hemi‐ovary served as an ungrafted control fragment. A polypropylene/polyglactin mesh was included between graft and base to separate the two structures, to help histological analysis. The mean graft performance time was 71 ± 8 min in the first group and 57 ± 10 min in the second. Freezing did not affect the number of primordial follicles. In the ungraft control fragments, the global anomaly rate (cytoplasm plus nuclear anomaly) increased after freezing (p < 0.05). Others results did not reach signification. Pelvic adhesion occurred only once. The post‐graft primordial follicle survival rate was 5.1 ± 2.8% in the non‐frozen group vs. 6.3 ± 2.3% after freezing/thawing. Kruskal–Wallis and Wilkoxon non‐parametric tests were used for statistical analysis. Laparoscopy seems to be a well‐adapted technique for ovarian tissue orthotopic autograft. The main follicle loss occurs before graft revascularization. Our orthotopic graft’s procedure has to be improved to obtain a better graft’s neovascularization, and to have a better long‐term post‐graft primordial follicle survival rate.
INERTIA OR INACTION? BLOOD PRESSURE MANAGEMENT AND CARDIOVASCULAR RISK IN DIABETES‡
Authors: Owen AJ , Retegan C , Rockell M , Jennings G , Reid CM 
Published: November 2008

SUMMARY

Diabetes is a significant risk factor for cardiovascular disease (CVD), but the presence of comorbidities, such as hypertension, markedly increases CVD risk. The aim of the present study was to determine the effectiveness of hypertension management in patients with diabetes.
The cvTRAC Study was a cross‐sectional study of CVD risk factors in primary care practices across Australia. General medical practitioners enrolled patients they considered to be at increased risk of CVD and reported on cardiovascular disease history, CVD risk factor levels and current therapy.
In all, 9857 men and 8332 women with diabetes participated in the study, with > ;85% having at least two CVD risk factors in addition to diabetes and 68% having a history of hypertension. Lost therapeutic benefit in diabetes patients with hypertension was seen in those who were failing to meet targets on antihypertensive drug therapy (therapeutic inertia: > ;73% of the hypertensive cohort), with a smaller proportion accounted for by those who met prescribing guidelines but were not being treated pharmacologically (treatment gap: 5.4% of the hypertensive cohort). Lack of compliance with lifestyle guidelines was estimated to account for over 8% of those not meeting blood pressure targets. Age (odds ratio (OR) 0.983, 95% confidence interval (CI) 0.980–0.986; P < 0.001), compliance with physical activity guidelines (OR 1.219, 95% CI 1.088–1.366; P = 0.001) and compliance with dietary guidelines (OR 1.298, 95% CI 1.188–1.420; P < 0.001) were independent predictors of target blood pressure attainment in the diabetic population.
Deficiencies in pharmacological and lifestyle‐related therapeutic strategies contribute to suboptimal hypertension management in diabetes. Therapeutic inertia is a greater contributor to lost therapeutic benefit than treatment gap in this population.
POSTOPERATIVE ANALGESIA INDUCED BY INTRATHECAL NEOSTIGMINE OR BETHANECHOL IN RATS
Authors: Prado WA , Dias TB 
Published: November 2008

SUMMARYCholinergic agonists and acetylcholinesterase inhibitors, such as neostigmine, produce a muscarinic receptor‐mediated antinociception in several animal species that depends on activation of spinal cholinergic neurons. However, neostigmine causes antinociception in sheep only in the early, and not late, postoperative period.In the present study, a model of postoperative pain was used to determine the antinociceptive effects of bethanechol (a muscarinic agonist) and neostigmine administered intrathecally 2, 24 or 48 h after a plantar incision in a rat hind paw. Changes in the threshold to punctate mechanical stimuli were evaluated using an automated electronic von Frey apparatus.Mechanical hyperalgesia was obtained following plantar incision, the effect being stronger during the immediate (2 h) than the late post‐surgical period. Bethanechol (15–90 µg/5 µL) or neostigmine (1–3 µg/5 µL) reduced incision‐induced mechanical hyperalgesia, the effects of both drugs being more intense during the immediate (2 h) than the late post‐surgical period.The ED50for bethanechol injected at 2, 24 and 48 h was 5.6, 51.9 and 82.5 µg/5 µL, respectively. The corresponding ED50for neostigmine was 1.62, 3.02 and 3.8 µg/5 µL, respectively.The decline in the antinociceptive potency of neostigmine with postoperative time is interpreted as resulting from a reduction in pain‐induced activation of acetylcholine‐releasing descending pathways. However, the similar behaviour of bethanechol in the same model points to an additional mechanism involving intrinsic changes in spinal muscarinic receptors.
MOLECULAR RECOGNITION OF THE DISORDERED DIHYDROPYRIDINE RECEPTOR II–III LOOP BY A CONSERVED SPRY DOMAIN OF THE TYPE 1 RYANODINE RECEPTOR
Authors: Tae Han‐Shen , Norris Nicole C , Cui Yanfang , Karunasekara Yamuna , Board Philip G , Dulhunty Angela F , Casarotto Marco G 
Published: November 2008

SUMMARY

The dihydropyridine receptor (DHPR) II–III loop is an intrinsically unstructured region made up of α‐helical and β‐turn secondary structure elements with the N and C termini in close spatial proximity.
The DHPR II–III loop interacts in vitro with a ryanodine receptor (RyR) 1 SPRY domain through α‐helical segments located in the A and B regions. Mutations within the A and B regions in the DHPR II–III loop alter the binding affinity to the SPRY2 domain.
The A and C peptides derived from DHPR II–III loop show negative cooperativity in binding to the SPRY2 domain.
The SPRY2 domain of the RyR1 (1085–1208) forms a β‐sheet sandwich structure flanked by variable loop regions. An acidic loop region of SPRY2 (1107–1121) forms part of a negatively charged cleft that is implicated in the binding of the DHPR II–III loop.
The mutant E1108A located in the negatively charged loop of SPRY2 reduces the binding affinity to the DHPR II–III loop.
Expression of nerve growth factor and tyrosine kinase receptor A and correlation with perineural invasion in pancreatic cancer
Authors: Ma Jun , Jiang Yumei , Jiang Yuhua , Sun Yan , Zhao Xueming 
Published: November 2008

AbstractBackground and Aim:  Perineural invasion (PNI) is one of the most common routes of invasion in pancreatic cancer and the exact mechanism is still not clear. The aim of the present study was to investigate the effect of nerve growth factor (NGF) and tyrosine kinase receptor A (TrkA) on PNI and to clarify the possible mechanism of PNI in pancreatic cancer.Methods:  Expressions of NGF/TrkA were examined in 51 human primary pancreatic cancer using immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT‐PCR). The molecular findings were correlated with PNI, clinicopathological parameters and expression of Ki‐67.Results:  Immunohistochemical analysis indicated that the presence and kind of PNI are prognostic parameters (P = 0.002,, P = 0.004). Tumors with high NGF expression exhibited more frequent presence of PNI (P = 0.033). NGF expression was significantly correlated with metastasis of lymph nodes and involvement of surgical margins (P = 0.006, 0.015). TrkA expression was significantly correlated with degree of PNI (P = 0.017). Negative correlations were found between expression of NGF/TrkA and Ki‐67. As shown by RT‐PCR, mRNA levels of NGF/TrkA with PNI were significantly higher than that without PNI.Conclusions:  In pancreatic cancer, overexpression of NGF may contribute to PNI by prompting the hyperplasia of nerves, restraining the apoptosis of tumor cells and specifically combining NGF and TrkA.
Is there a link between food and intestinal microbes and the occurrence of Crohn's disease and ulcerative colitis?
Authors: Asakura Hitoshi , Suzuki Kenji , Kitahora Tetsuji , Morizane Toshio 
Published: November 2008

AbstractThe pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) is not fully understood. The interaction between intestinal environmental factors of food and intestinal microbes and the immunological system of hosts seems to be an important aspect. We have reviewed the relationship of the daily consumption of dietary animal meat and fats, dairy products, sugar, and other factors that may be linked to the occurrence of CD and UC from the literature and Japanese epidemiological data. In the present study, we reviewed the association between food and intestinal microbes and other factors contributing to the occurence of inflammatory bowel disease (IBD) from epidemiological data and case‐control studies of IBD in the literature that appeared on Medline, and assessed the reports of intestinal microbes involved in the occurrence of IBD. We found several papers describing the positive association of animal meat and sweets and sugar with the occurrence of CD and UC. An analysis of Japanese epidemiological data suggested that the registered number of patients with CD or UC started to increase more than 20 years after an increased daily consumption of dietary animal meat and fats, and milk and dairy products, and after a decreased consumption of rice. Many studies implied a positive role of intestinal microbes in the occurrence of IBD. Intestinal environmental factors, such as Westernized food and intestinal microbes, seem to be involved in the increased occurrence of IBD.
Gastroesophageal reflux disease: An Asian perspective
Authors: Wu Justin CY 
Published: November 2008

AbstractThe prevalence of gastroesophageal reflux disease (GERD) ranges from 2.5% to 7.1% in most population‐based studies in Asia. There is evidence that GERD and its complications are rising, coinciding with a decline in Helicobacter pylori (H. pylori) infection. Asian GERD patients share similar risk factors and pathophysiological mechanisms with their Western counterparts. Possible causes for the lower prevalence of GERD include less obesity and hiatus hernia, a lesser degree of esophageal dysmotility, a high prevalence of virulent strains of H. pylori, and low awareness. Owing to the lack of precise translation for ‘heartburn’ in most Asian languages, reflux symptoms are often overlooked or misinterpreted as dyspepsia or chest pain. Furthermore, a symptom‐based diagnosis with a therapeutic trial of the proton pump inhibitor (PPI) may be hampered by the high prevalence of H. pylori‐related disease. The risk stratification for prompt endoscopy, use of a locally‐validated, diagnostic symptom questionnaire, and response to H. pylori‘test and treat’ help improve the accuracy of the PPI test for diagnoses. PPI remain the gold standard treatment, and ‘on‐demand’ PPI have been shown to be a cost‐effective, long‐term treatment. The clinical course of GERD is benign in most patients in Asia. The risk of progression from non‐erosive reflux disease to erosive esophagitis is low, and treatment response to a conventional dose of PPI is generally higher. Although H. pylori eradication may lead to more resilient GERD in a subset of patients, the benefits of H. pylori eradication outweigh the risks, especially in Asian populations with a high incidence of gastric cancer.