bluuebunny/crossref_metadata_2025 huggingface dataset:
The Protein Kinase SnRK2.6 Mediates the Regulation of Sucrose Metabolism and Plant Growth in Arabidopsis
Authors: Zheng Zhifu , Xu Xiaoping , Crosley Rodney A. , Greenwalt Scott A. , Sun Yuejin , Blakeslee Beth , Wang Lizhen , Ni Weiting , Sopko Megan S. , Yao Chenglin , Yau Kerrm , Burton Stephanie , Zhuang Meibao , McCaskill David G. , Gachotte Daniel , Thompson Mark , Greene Thomas W.
Published: March 2010

In higher plants, three subfamilies of sucrose nonfermenting-1 (Snf1)-related protein kinases have evolved. While the Snf1-related protein kinase 1 (SnRK1) subfamily has been shown to share pivotal roles with the orthologous yeast Snf1 and mammalian AMP-activated protein kinase in modulating energy and metabolic homeostasis, the functional significance of the two plant-specific subfamilies SnRK2 and SnRK3 in these critical processes is poorly understood. We show here that SnRK2.6, previously identified as crucial in the control of stomatal aperture by abscisic acid (ABA), has a broad expression pattern and participates in the regulation of plant primary metabolism. Inactivation of this gene reduced oil synthesis in Arabidopsis (Arabidopsis thaliana) seeds, whereas its overexpression increased Suc synthesis and fatty acid desaturation in the leaves. Notably, the metabolic alterations in the SnRK2.6 overexpressors were accompanied by amelioration of those physiological processes that require high levels of carbon and energy input, such as plant growth and seed production. However, the mechanisms underlying these functionalities could not be solely attributed to the role of SnRK2.6 as a positive regulator of ABA signaling, although we demonstrate that this kinase confers ABA hypersensitivity during seedling growth. Collectively, our results suggest that SnRK2.6 mediates hormonal and metabolic regulation of plant growth and development and that, besides the SnRK1 kinases, SnRK2.6 is also implicated in the regulation of metabolic homeostasis in plants.
Analytical description of the scattering of cellulose nanocrystals in tracheid wood cells
Authors: Ogurreck Malte , Müller Martin
Published: March 2010

Tracheid cells are complex structures. The cellulose nanocrystals are wound in helices around the tracheid cell axis. The microfibril angle describes the angle between the cellulose crystals and the cell axis. Furthermore, the cross-sectional shape of tracheids varies widely, ranging from square to round. These parameters affect the scattering geometry and thus the experimental scattering signal. In an experiment, the macroscopic sample orientation relative to the beam is a further variable. Here, a description is presented that allows the calculation of azimuthal scattering patterns for anyhklreflection from cellulose nanocrystals in tracheid cells of any orientation. Additionally, this model can be used to describe fibrillar aggregates with an additional level of organization that surpasses an ideal fiber texture, for example pairs of twisted fibers.
Photocrystallography – design and methodology for the use of a light-emitting diode device
Authors: Brayshaw Simon K. , Knight Jason W. , Raithby Paul R. , Savarese Teresa L. , Schiffers Stefanie , Teat Simon J. , Warren John E. , Warren Mark R.
Published: March 2010

With the increase in interest in photocrystallographic experiments, the use of light-emitting diodes (LEDs) provides an alternative, low-budget light source (by comparison to lasers) and allows photocrystallographic experiments to be carried out readily. Here the design of an LED array device suitable for use in single-crystal X-ray diffraction experiments is reported, and the experimental methodology used for determining the structures of metastable species is described.
Frequent alterations of the candidate genes hMLH1, ITGA9 and RBSP3 in early dysplastic lesions of head and neck: Clinical and prognostic significance
Authors: Ghosh Amlan , Ghosh Susmita , Maiti Guru Prasad , Sabbir Mohammad Golam , Zabarovsky Eugene R. , Roy Anup , Roychoudhury Susanta , Panda Chinmay Kumar
Published: March 2010

To understand the association between candidate tumor suppressor genes (TSGs) human mismatch repair protein homologue 1 (hMLH1), AP20 region gene 1 (APRG1), integrin α RLC (ITGA9), RB1 serine phosphates from human chromosome 3 (RBSP3) at chromosomal 3p22.3 region and development of head and neck squamous cell carcinoma (HNSCC), alterations (deletion/promoter methylation/expression) of these genes were analyzed in 65 dysplastic lesions and 84 HNSCC samples. Clinicopathological correlations were made with alterations of the genes. In HNSCC, deletion frequencies of hMLH1, ITGA9, and RBSP3 were comparatively higher than APRG1. Overall alterations (deletion/methylation) of hMLH1, ITGA9, and RBSP3 were high (45–55%) in mild dysplasia and comparable in subsequent stages of tumor progression. Quantitative RT‐PCR analysis showed reduced expression of these genes in tumors concordant to their molecular alterations. An in vitro demethylation experiment by 5‐aza‐2′‐deoxycytidine confirmed the promoter hypermethylation of RBSP3 in Hep2 and UPCI:SCC084 cell lines. Functionally less‐active RBSP3A isoform was predominant in tumor tissues contrary to the adjacent normal tissue of tumors where more active RBSP3B isoform was prevalent. In immunohistochemical analysis, intense nuclear staining of hMLH1 and pRB (phosphorylated RB, the substrate of RBSP3) proteins were seen in the basal layer of normal epithelium. In tumors, concordance was seen between (i) low/intermediate level of hMLH1 expression and its molecular alterations; and (ii) intense nuclear staining of pRB and RBSP3 alterations. Poor patient outcome was seen with hMLH1 and RBSP3 alterations. Moreover, in absence of human papilloma virus (HPV) infection, tobacco‐addicted patients with hMLH1, RBSP3 alterations, and nodal invasions showed poor prognosis. Thus our data suggests that dysregulation of hMLH1, ITGA9, and RBSP3 associated multiple cellular pathways are needed for the development of early dysplastic lesions of the head and neck. (Cancer Sci 2010)
Bcl‐XL and STAT3 mediate malignant actions of γ‐irradiation in lung cancer cells
Authors: Ho Jin‐Nyoung , Kang Ga Young , Lee Seung‐Sook , Kim Jongdoo , Bae In Hwa , Hwang Sang‐Gu , Um Hong‐Duck
Published: March 2010

Previous reports suggest that, in addition to its therapeutic effects, ionizing radiation (IR) increases the invasiveness of surviving cancer cells. Here, we demonstrate that this activity of IR in lung cancer cells is mediated by a signaling pathway involving p38 kinase, phosphoinositide 3‐kinase, Akt, and matrix metalloproteinase (MMP‐2). The invasion‐promoting doses of IR also increased and reduced the levels of vimentin and E‐cadherin, respectively, both of which are markers for the epithelial–mesenchymal transition (EMT). Interestingly, all of these malignant actions of IR were mimicked by the overexpression of Bcl‐XL, a pro‐survival member of the Bcl‐2 family, in lung cancer cells. Moreover, both RNA and protein levels of Bcl‐XL were elevated upon irradiation of the cells, and the prevention of this event using small‐interfering RNAs of Bcl‐XL reduced the ability of IR to promote invasion signals and EMT‐associated events. This suggests that Bcl‐XL functions as a signaling mediator of the malignant effects of IR. It was also demonstrated that IR enhances signal transducer and activator of transcription 3 (STAT3) phosphorylation, and the reduction of STAT3 levels via RNA interference prevented IR‐induced Bcl‐XL accumulation, and thus all the tested Bcl‐XL‐dependent events. Overall, the data suggest that IR induces Bcl‐XL accumulation via STAT3, which then promotes cancer cell invasion and EMT‐associated markers. Our findings demonstrate a novel function of Bcl‐XL in cancer, and also advance our understanding of the malignant actions of IR significantly. (Cancer Sci 2010)
Tobraviruses—plant pathogens and tools for biotechnology
Authors: MACFARLANE STUART A.
Published: March 2010

The tobraviruses,Tobacco rattle virus(TRV),Pea early‐browning virus(PEBV) andPepper ringspot virus(PepRSV), are positive‐strand RNA viruses with rod‐shaped virus particles that are transmitted between plants by trichodorid nematodes. As a group, these viruses infect many plant species, with TRV having the widest host range. Recent studies have begun to dissect the interaction of TRV with potato, currently the most commercially important crop disease caused by any of the tobraviruses. As well as being successful plant pathogens, these viruses have become widely used as vectors for expression in plants of nonviral proteins or, more frequently, as initiators of virus‐induced gene silencing (VIGS). Precisely why tobraviruses should be so effective as VIGS vectors is not known; however, molecular studies of the mode of action of the tobravirus silencing suppressor protein are shedding some light on this process.
A New Method for the Determination of Carbon Monoxide in Blood
Authors: WKNNESLAND R.
Published: March 2010

A new method for the determination of carbon monoxide in blood is described. The blood is brought into an Erlenmeyer flask, mixed with water and its carbon monoxide hemoglobin is converted into acid hematin by addition of sulfuric acid. The carbon monoxide liberated passes into another Erlenmeyer flask, which has been connected with the first one by an airtight rubber cuff and contains a known solution of palladium chloride. A corresponding quantity of the latter is reduced to metallic palladium. Excessive palladium chloride is precipitated by a known quantity of potassium iodide, and the excess of the latter is titrated after the principle of Dupré‐Winkler. The method is well fitted for micro‐analysis.
A Parapharyngeal Method of Hypophysectomy in Babbits
Authors: JACOBSOHN DORA , WESTMAN AXEL
Published: March 2010

A technic of hypophysectomy in rabbits is described. The parapharyngeal route is taken and the operation done according to the principles of hypophysectomy in rats, but modified to suit the anatomy of the rabbit. The method has great advantages. It enables direct inspection of the field of operation. The operative risk is slight. The mortality is extremely low.

This work has been aided by a grant from « Stiftelsen Therese och Johan Anderssons Minne», Stockholm.
Effect of lesogaberan, a novel GABAB‐receptor agonist, on transient lower oesophageal sphincter relaxations in male subjects
Authors: BOECKXSTAENS G. E. , RYDHOLM H. , LEI A. , ADLER J. , RUTH M.
Published: March 2010

Aliment Pharmacol Ther 31, 1208–1217

Background  Transient lower oesophageal sphincter relaxations (TLESRs) are a major mechanism behind gastro‐oesophageal reflux disease (GERD).

Aim  To assess the effect of lesogaberan (AZD3355) – a novel peripherally active GABAB receptor agonist – on TLESRs.

Methods  Twenty‐four healthy men were enrolled in this single‐blind, placebo‐controlled, randomized, single‐centre, three‐period crossover phase 1 study. Subjects were randomized to receive single oral doses of lesogaberan (0.8 mg/kg), baclofen (40 mg) and placebo, separated by washout periods of ≤7 days. Subjects finished a meal 1 h after the dose. Oesophageal manometry and pH‐metry measurements were taken during the 3 h after the meal.

Results  Twenty‐one subjects completed the study. Compared with placebo, lesogaberan 0.8 mg/kg significantly reduced the number of TLESRs by 36% [geometric mean ratio (GMR): 0.64; 95% confidence interval (CI): 0.51–0.82] and significantly reduced the number of acid reflux episodes (mean reduction: 1.6; 95% CI: 0.34–2.9). Lesogaberan also significantly increased lower oesophageal sphincter (LES) pressure by 39% compared with placebo (GMR: 1.39; 95% CI: 1.18–1.64). Comparable results were observed with baclofen. Similar numbers of adverse events were reported by subjects taking lesogaberan and placebo.

Conclusion  Compared with placebo, lesogaberan significantly reduced TLESRs and acid reflux episodes and increased LES pressure.
Antacids and dietary supplements with an influence on the gastric pH increase the risk for food sensitization
Authors: Pali‐Schöll I. , Herzog R. , Wallmann J. , Szalai K. , Brunner R. , Lukschal A. , Karagiannis P. , Diesner S. C. , Jensen‐Jarolim E.
Published: March 2010

Background
Elevation of the gastric pH increases the risk for sensitization against food allergens by hindering protein breakdown. This can be caused by acid‐suppressing medication like sucralphate, H2‐receptor blockers and proton pump inhibitors, as shown in recent murine experimental and human observational studies.

Objective
The aim of the present study was to assess the sensitization capacity of the dietary supplement base powder and of over‐the‐counter antacids.

Methods
Changes of the pH as well as of protein digestion due to base powder or antacids were measured in vitro. To examine the in vivo influence, BALB/c mice were fed codfish extract with one of the acid‐suppressing substances. Read‐out of antibody levels in the sera, of cytokine levels of stimulated splenocytes and of intradermal skin tests was performed.

Results
The pH of hydrochloric acid was substantially increased in vitro by base powder as well as antacids in a time‐ and dose‐dependent manner. This elevation hindered the digestion of codfish proteins in vitro. A significant increase in codfish‐specific IgE antibodies was found in the groups fed codfish combined with Rennie® Antacidum or with base powder; the latter also showed significantly elevated IgG1 and IgG2a levels. The induction of an anaphylactic immune response was proven by positive results in intradermal skin tests.

Conclusions
Antacids and dietary supplements influencing the gastric pH increase the risk for sensitization against allergenic food proteins. As these substances are commonly used in the general population without consulting a physician, our data may have a major practical and clinical impact.

Cite this as: I. Pali‐Schöll, R. Herzog, J. Wallmann, K. Szalai, R. Brunner, A. Lukschal, P. Karagiannis, S. C. Diesner and E. Jensen‐Jarolim, Clinical & Experimental Allergy, 2010 (40) 1091–1098.
Plasma levels of matrix metalloproteinase‐9 in chronic urticaria patients correlate with disease severity and C‐reactive protein but not with circulating histamine‐releasing factors
Authors: Tedeschi A. , Asero R. , Lorini M. , Marzano A. V. , Cugno M.
Published: March 2010

Background
Matrix metalloproteinase‐9 (MMP‐9) is an endopeptidase produced by many inflammatory cells that has been found in increased amounts in plasma from patients with chronic urticaria (CU).

Objective
To evaluate plasma levels of MMP‐9 and its tissue inhibitor of metalloproteinase‐1 (TIMP‐1) in CU patients in relation with disease severity, C‐reactive protein (CRP) and circulating histamine‐releasing factors.

Methods
Fifty‐two consecutive CU patients were included in the study and disease activity was graded from 0 to 3. Plasma MMP‐9, TIMP‐1 and CRP levels were measured by enzyme immunoassays. Circulating histamine‐releasing factors were assessed using in vivo (autologous serum skin test) and in vitro (basophil histamine release) tests. Seven CU patients were studied both during active disease and during remission. Thirty healthy subjects were used as normal controls.

Results
Plasma levels of MMP‐9, TIMP‐1 and CRP were significantly higher in CU patients than in healthy controls (P=0.0001, 0.003 and 0.005, respectively) and a trend towards a higher MMP‐9/TIMP‐1 molar ratio was found (P=0.051). A significant correlation was found between plasma MMP‐9 levels and urticaria severity score (r=0.48, P<0.0001). CRP levels correlated with MMP‐9 levels (r=0.37, P=0.008) and CU severity score (r=0.52, P=0.0001), but not with TIMP‐1 (r=0.13) concentrations. MMP‐9, TIMP‐1 and CRP plasma levels and MMP‐9/TIMP‐1 molar ratio did not differ in patients either with or without an evidence of circulating histamine‐releasing factors. Seven patients evaluated during remission showed a significant reduction of MMP‐9 and CRP plasma levels.

Conclusion
Plasma levels of MMP‐9 and its inhibitor TIMP‐1 are increased in CU patients. MMP‐9 levels are associated with disease severity and CRP levels, but not with skin reactivity to autologous serum and with circulating histamine‐releasing factors. These findings suggest that in CU there is an ongoing inflammatory process independent of the presence of circulating histamine‐releasing factors.
Aliskiren ameliorates chlorhexidine digluconate‐induced peritoneal fibrosis in rats
Authors: Ke Chun‐Yen , Lee Chia‐Chi , Lee Chung‐Jen , Subeq Yi‐Maun , Lee Ru‐Ping , Hsu Bang‐Gee
Published: March 2010

Eur J Clin Invest 2010; 40 (4): 301–309

Background  Peritoneal fibrosis (PF) is a recognized complication of long‐term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of aliskiren on chlorhexidine digluconate‐induced PF in rats.

Materials and methods  The PF was induced in Sprague–Dawley rats by daily administration of 0·5 mL 0·1% chlorhexidine digluconate in normal saline via PD tube for 1 week. Rats received daily intravenous injections of low‐dose aliskiren (1 mg kg−1) or high‐dose aliskiren (10 mg kg−1) for 1 week. After 7 days, conventional 4·25% Dianeal (30 mL) was administered via a PD catheter with a dwell time of 4 h and assessed of peritoneal function. At the end of dialysis, rats were sacrificed and the liver peritoneum was harvested for microscopically and immunohistochemistry.

Results  There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D4/P4 urea level was reduced, the D4/D0 glucose level, serum and dialysate transforming growth factor‐β1 (TGF‐β1) level was increased, the liver peritoneum was markedly thicker, and the expression of TGF‐β1, alpha‐smooth muscle actin (α‐SMA), fibronectin, collagen, and vascular endothelial growth factor (VEGF) were elevated in the PS group compared with the vehicle group. Aliskiren decreased the serum and dialysate TGF‐β1 level, decreased the thickness of the liver peritoneum, and decreased the expression of TGF‐β1, α‐SMA, fibronectin, collagen, and VEGF‐positive cells in liver peritoneum. Moreover, high‐dose aliskiren had better protective effects against PF than low dose in rats.

Conclusions  Aliskiren protected against chlorhexidine digluconate‐induced PF in rats by decreasing TGF‐β1 production.
N2O emissions from an irrigated and non‐irrigated organic soil in eastern Canada as influenced by N fertilizer addition
Authors: Rochette P. , Tremblay N. , Fallon E. , Angers D. A. , Chantigny M. H. , MacDonald J. D. , Bertrand N. , Parent L.‐É.
Published: March 2010

Drainage and cultivation of organic soils often result in large nitrous oxide (N2O) emissions. The objective of this study was to assess the impacts of nitrogen (N) fertilizer on N2O emissions from a cultivated organic soil located south of Montréal, QC, Canada, drained in 1930 and used since then for vegetable production. Fluxes of N2O were measured weekly from May 2004 to November 2005 when snow cover was absent in irrigated and non‐irrigated plots receiving 0, 100 or 150 kg N ha−1 as NH4NO3. Soil mineral N content, gas concentrations, temperature, water table height and water content were also measured to help explain variations in N2O emissions. Annual emissions during the experiment were large, ranging from 3.6 to 40.2 kg N2O‐N ha−1 year−1. The N2O emissions were decreased by N fertilizer addition in the non‐irrigated site but not in the irrigated site. The absence of a positive influence of soil mineral N content on N2O emissions was probably in part because up to 571 kg N ha−1 were mineralized during the snow‐free season. Emissions of N2O were positively correlated to soil CO2 emissions and to variables associated with the extent of soil aeration such as soil oxygen concentration, precipitation and soil water table height, thereby indicating that soil moisture/aeration and carbon bioavailability were the main controls of N2O emission. The large N2O emissions observed in this study indicate that drained cultivated organic soils in eastern Canada have a potential for N2O‐N losses similar to, or greater than, organic soils located in northern Europe.
Molecular changes in particulate organic matter (POM) in a typical Chinese paddy soil under different long‐term fertilizer treatments
Authors: Zhou P. , Pan G. X. , Spaccini R. , Piccolo A.
Published: March 2010

A combination of solid‐state CPMAS‐13C‐NMR and TMAH thermochemolysis‐GC/MS was applied to investigate the molecular composition of particulate organic matter (POM) separated from a Chinese paddy soil, from the Tai Lake region, under a long‐term field experiment with different fertilizer treatments. The treatments were: (i) no fertilizer application (NF), (ii) chemical fertilizers only (CF), (iii) chemical fertilizer plus pig manure (CFM) and (iv) chemical fertilizer plus crop straw (CFS). CPMAS‐13C‐NMR spectra showed that POM from all treated plots was rich in O‐alkyl‐C compounds, followed by alkyl‐C and aromatic‐C compounds. However, as compared with a control (NF), POM under CFM and CFS treatments exhibited a smaller relative O‐alkyl‐C content and a larger contribution of aromatic‐C and alkyl‐C, thus increasing both aromaticity and hydrophobicity and, hence, recalcitrance of POM samples. Thermochemolysis of POM from all treatments demonstrated a dominance of aliphatic and lignin‐derived compounds. However, the distribution of lignin monomers (p‐hydroxyphenyl, P, guaiacyl, G, and syringyl, S) revealed significant differences among the treatments. The relative distribution of lignin P, G and S monomers in NF, CF and CFS indicated a preferential contribution of annual crops and maize straw, as compared with that found for CFM. Concomitantly, a larger content of aliphatic thermochemolysis derivatives was found for CFS and CFM. The relative increase of aliphatic molecules in CFS was attributed to hydrophobic polyesters from higher plants. In the CF and CFM systems, the presence of aliphatic components of microbial origin suggested a greater microbial activity in comparison with NF and CFS. The combined application of solid state CPMAS‐13C‐NMR and TMAH thermochemolysis‐GC/MS can be used to assess effectively the accumulation of recalcitrant organic compounds in soil POM under long‐term fertilizer application with organic biomass. It is thus inferred that soil organic matter stabilization by molecular recalcitrance contributes to carbon sequestration in Chinese paddy soils under long‐term managements.
Effects of low‐molecular‐weight organic compounds on sulphur immobilization and re‐mineralization and extraction of immobilized sulphur by hot‐water and acid hydrolysis
Authors: Vong P.‐C. , Piutti S. , Slezack‐Deschaumes S. , Benizri E. , Guckert A.
Published: March 2010

We examined the effects of salicylate, glutamate and glucose on sulphur (S) immobilization and re‐mineralization in three calcareous soils: from arable, fallow and forest managements. Each of the three substrates, at a single rate of carbon (1000 mg C kg−1 soil) was added to the three soils and then incubated with NaSO4 plus Na2SO4 for 1, 2, 6 or 12 weeks prior to analysis. The extraction of the immobilized S was performed with either hot water (HW‐S) or 3 m hydrochloric acid (HCl‐S). Except for the forest soil, the average amounts of immobilized S increased in the order control < salicylate < glutamate < glucose. Across all soils, substrate addition significantly decreased the average value of HCl‐S expressed as a percentage of immobilized S compared with that of the control. The decreases in HCl‐S (58 − 100%) were substrate‐ and time‐independent, suggesting a heterogeneous action of HCl. In contrast, except for the forest soil, we found substantial declines in the average percentage values of HW‐S (21 − 75% of the immobilized S) in the order control > salicylate > glutamate = glucose, suggesting that the hot‐water action was substrate dependent. In addition, the proportion of HW‐S decreased with increasing incubation time, indicating that the youngest immobilized S was the most labile. Thus, hot water extracted more homogeneous S compounds than HCl. Sulphur immobilization induced by glutamate and glucose produced more recalcitrant S products (small quantities of 35S re‐mineralization) than that induced by salicylate. Glutamate tended to generate more recalcitrant S compounds than glucose. Hot‐water extractable S was a valuable and rapid indicator of readily labile organic S. Consequent microbial S immobilization resulting from glucose or glutamate addition was followed by a small rate of re‐mineralization of immobilized S.
Anti‐apoptotic effect of the basic helix‐loop‐helix (bHLH) transcription factor DEC2 in human breast cancer cells
Authors: Liu Yang , Sato Fuyuki , Kawamoto Takeshi , Fujimoto Katsumi , Morohashi Satoko , Akasaka Harue , Kondo Jun , Wu Yunyan , Noshiro Mitsuhide , Kato Yukio , Kijima Hiroshi
Published: March 2010

DEC1 (BHLHB2/Stra13/Sharp2) and DEC2 (BHLHB3/Sharp1) are basic helix‐loop‐helix (bHLH) transcription factors that are involved in circadian rhythms, differentiation and the responses to hypoxia. We examined whether DEC1 and DEC2 are involved in apoptosis regulation, in human breast cancer MCF‐7 cells. We found that siRNA‐mediated knockdown of DEC2 resulted in marked enhancement of apoptosis compared with that in control cells transfected with nonspecific siRNA. However, knockdown of DEC1 by siRNA did not affect cell survival. Knockdown of DEC2 affected the expression of mRNA or proteins related to apoptosis, such as Fas, c‐Myc, caspase‐8, poly (ADP‐ribose) polymerase (PARP) and Bax. We also showed that tumor necrosis factor‐α (TNF‐α) up‐regulates the expression of DEC1 and DEC2. DEC2 over‐expression caused by the transfection of an expression vector reduced the amounts of cleaved PARP and caspase‐8 induced by TNF‐α treatment, whereas DEC1 over‐expression increased it. Finally, we revealed that treatment with double knockdown against both DEC1 and DEC2 decreased the amounts of cleaved PARP and caspase‐8 induced by DEC2 siRNA with or without TNF‐α. These data indicate that DEC2 has an anti‐apoptotic effect, whereas DEC1 has a pro‐apoptotic effect, which are involved in the balance of survival of human breast cancer MCF‐7 cells.
Tumor growth suppression in vivo by overexpression of the circadian component, PER2
Authors: Miyazaki Koyomi , Wakabayashi Miyuki , Hara Yasuhiro , Ishida Norio
Published: March 2010

Some reports have indicated that the core clock gene, Per2 regulates the cell cycle, immune system and neural functions. To understand the effects of PER2 on tumor growth in vivo, stable transformants of murine sarcoma 180 (S‐180) cell lines expressing different levels of PER2 were established. The growth of stable PER2 transformants in vivo was significantly and dose‐dependently suppressed according to the amount of PER2 expressed, indicating that PER2 plays a role in the growth suppression of sarcoma cells. The anchorage‐dependent and ‐independent growth in vitro and expression of the clock controlled cell‐cycle related genes, wee1, myc, and VEGF were not altered in stable PER2 transformants. In contrast, susceptibility to murine natural killer (NK) cell cytolytic activity was enhanced in PER2 transformants. Furthermore, PER2 transformants suppressed cell motility and reduced fibronectin expression, but the expression of integrin receptors was not affected. These results suggest that sarcoma cells overexpressing PER2 suppress tumors in vivo by changing the nature of tumor cell adhesion.
Lack of oxygen in articular cartilage: consequences for chondrocyte biology
Authors: Lafont Jérôme E.
Published: March 2010

Controlling the chondrocytes phenotype remains a major issue for cartilage repair strategies. These cells are crucial for the biomechanical properties and cartilage integrity because they are responsible of the secretion of a specific matrix. But chondrocyte dedifferentiation is frequently observed in cartilage pathology as well as in tissue culture, making their study more difficult. Given that normal articular cartilage is hypoxic, chondrocytes have a specific and adapted response to low oxygen environment. While huge progress has been performed on deciphering intracellular hypoxia signalling the last few years, nothing was known about the particular case of the chondrocyte biology in response to hypoxia. Recent findings in this growing field showed crucial influence of the hypoxia signalling on chondrocytes physiology and raised new potential targets to repair cartilage and maintain tissue integrity. This review will thus focus on describing hypoxia‐mediated chondrocyte function in the native articular cartilage.
Searching for the Hebb effect in Down syndrome: evidence for a dissociation between verbal short‐term memory and domain‐general learning of serial order
Authors: Mosse E. K. , Jarrold C.
Published: March 2010

Background  The Hebb effect is a form of repetition‐driven long‐term learning that is thought to provide an analogue for the processes involved in new word learning. Other evidence suggests that verbal short‐term memory also constrains now vocabulary acquisition, but if the Hebb effect is independent of short‐term memory, then it may be possible to demonstrate its preservation in a sample of individuals with Down syndrome, who typically show a verbal short‐term memory deficit alongside surprising relative strengths in vocabulary.

Methods  In two experiments, individuals both with and without Down syndrome (matched for receptive vocabulary) completed immediate serial recall tasks incorporating a Hebb repetition paradigm in either verbal or visuospatial conditions.

Results  Both groups demonstrated equivalent benefit from Hebb repetition, despite individuals with Down syndrome showing significantly lower verbal short‐term memory spans. The resultant Hebb effect was equivalent across verbal and visuospatial domains.

Conclusions  These studies suggest that the Hebb effect is essentially preserved within Down syndrome, implying that explicit verbal short‐term memory is dissociable from potentially more implicit Hebb learning. The relative strength in receptive vocabulary observed in Down syndrome may therefore be supported by largely intact long‐term as opposed to short‐term serial order learning. This in turn may have implications for teaching methods and interventions that present new phonological material to individuals with Down syndrome.
Working memory and educational achievement in children with intellectual disabilities
Authors: Henry L. , Winfield J.
Published: March 2010

Background  There is little previous research examining whether measures of working memory are related to educational achievement in children with intellectual disabilities (ID).

Methods  A battery of working memory and achievement measures was administered to 11‐ to 12‐year‐old children with ID; younger typically developing children of comparable mental age were also assessed.

Results  The working memory measures that assessed phonological short‐term memory (PSTM) accounted for the most variance in reading and spelling in children with ID, whereas the working memory measures that assessed central executive‐loaded working memory (CELWM) accounted for the most variance in number skills. These relationships were broadly similar among typically developing children.

Conclusions  Compensatory strategies for weak PSTM may help to improve reading and spelling skills in children with ID, whereas reducing CELWM loads may be more helpful in aiding their number skills.
High frequency of ETFDH c.250G>A mutation in Taiwanese patients with late‐onset lipid storage myopathy
Authors: Lan M‐Y , Fu M‐H , Liu Y‐F , Huang C‐C , Chang Y‐Y , Liu J‐S , Peng C‐H , Chen S‐S
Published: March 2010

Lan M‐Y, Fu M‐H, Liu Y‐F, Huang C‐C, Chang Y‐Y, Liu J‐S, Peng C‐H, Chen S‐S. High frequency of ETFDH c.250G>A mutation in Taiwanese patients with late‐onset lipid storage myopathy.

Lipid storage myopathies (LSMs) are characterized pathologically by the accumulation of lipid droplets in muscle fibers due to impaired cellular lipid metabolism. The purpose of this study was to determine etiologies and genetic mutations associated with LSMs in ethnic Han Taiwanese. The usefulness of the blood acylcarnitine (AC) profile for diagnosing LSMs in adult patients was also investigated. Nine patients were diagnosed with late‐onset LSMs following a review of muscle biopsies and medical records and were recruited retrospectively. Genetic studies were performed to detect mutations in the SLC22A5 for primary carnitine deficiency, PNPLA2 for neutral lipid storage disease with myopathy, ABHD5 for neutral lipid storage disease with ichthyosis, ETFDH for multiple acyl‐CoA dehydrogenation deficiency (MADD), and CPT2 for carnitine palmitoyltransferase II deficiency. Blood AC levels were measured by tandem mass spectrometry. The mutation c.250G>A in ETFDH was detected in seven (78%) patients, six of whom were homozygous for the variant. Patients with ETFDH mutations had elevated blood levels of ACs ranging from C8 to C16 species, a pattern consistent with MADD. ETFDH c.250G>A mutation is common in Taiwanese patients with late‐onset LSMs. The blood AC profile is a sensitive biochemical marker for diagnosing MADD arising from ETFDH mutations in adults.
Seasonal variation in nitrous oxide and methane emissions from subtropical estuary and coastal mangrove sediments, Australia
Authors: Allen D. , Dalal R. C. , Rennenberg H. , Schmidt S.
Published: March 2010

Mangrove sediments can act as sources of the greenhouse trace gases, nitrous oxide (N2O) and methane (CH4). Confident reporting of trace gas emissions from mangrove sediments at local levels is important for regional emissions inventories, since small changes in N2O and CH4 fluxes greatly influence greenhouse gas budgets due to their high global warming potentials. It is also important to identify the drivers of trace gas emission, to prioritise management for minimising emissions. We measured N2O and CH4 fluxes and abiotic sediment parameters at midday low tide in winter and summer seasons, at four sites (27°33′S, 152°59′E) ranging from estuary to ocean sub‐tropical mangrove sediments, having varied anthropogenic impacts. At all sites, sediment N2O and CH4 emissions were significantly lower during winter (7–26 μg N2O m−2·h−1; 47–466 μg CH4 m−2·h−1) compared to summer (28–202 μg N2O m−2·h−1; 247–1570 μg CH4 m−2·h−1). Sediment temperature, ranging from 18 to 33 °C, strongly influenced N2O and CH4 emissions. Highest emissions (202 μg N2O m−2·h−1, 1570 μg CH4 m−2·h−1) were detected at human‐impacted estuary sites, which generally had higher total carbon (<8%) and total nitrogen (<0.4%) in sediments and reduced salinity (<16 dS·m−1). Large between‐site variation highlights the need for regular monitoring of sub‐tropical mangroves to capture short‐lived, episodic N2O and CH4 flux events that are affected by sediment biophysico‐chemical conditions at site level. This is important, particularly at sites receiving anthropogenic nutrients, and that have variable freshwater inputs and tidal hydrology.
Identification and application of a DNA‐based marker that is diagnostic for the pepper (Capsicum annuum) bacterial spot resistance gene Bs3
Authors: Römer P. , Jordan T. , Lahaye T.
Published: March 2010

With 1 figure and 1 table

The pepper (Capsicum annuum) disease resistance gene Bs3 mediates recognition of avrBs3‐expressing strains of the bacterial spot pathogen Xanthomonas campestris pv. vesicatoria. We established the co‐dominant DNA marker PR‐Bs3 that detects a functional nucleotide polymorphism in the Bs3 promoter. Analysis of 20 F2 segregants demonstrated complete linkage between PR‐Bs3 and Bs3 resistance. Furthermore the analysis of 17 Capsicum accessions from diverse geographical origins demonstrated that PR‐Bs3 was diagnostic for Bs3 resistance in all cases. Given that marker PR‐Bs3 allows the identification of Bs3 resistant lines in a co‐dominant fashion it will be a valuable tool for marker assisted selection of Bs3 resistant lines in bacterial spot resistance breeding programs.
Attenuation of warm ischemia–reperfusion injury in the liver by bucillamine through decreased neutrophil activation and Bax/Bcl‐2 modulation
Authors: Junnarkar Sameer P , Tapuria Niteen , Mani Alireza , Dijk Sas , Fuller Barry , Seifalian Alexander M , Davidson Brian R
Published: March 2010

Background and Aim:  Liver transplantation and resection surgery involve a period of ischemia and reperfusion to the liver, which initiates an inflammatory cascade resulting in liver and remote organ injury. Bucillamine is a low molecular weight thiol antioxidant that is capable of rapidly entering cells. We hypothesized that bucillamine acts by replenishing glutathione levels, thus reducing neutrophil activation, modulating Bax/Bcl‐2 expression, and subsequently, attenuating the effects of warm ischemia–reperfusion injury (IRI) in the liver.

Methods:  The effect of bucillamine was studied in a rat model of liver IRI with 45 min of partial (70%) liver ischemia and 3 h of reperfusion. Liver injury was assessed by measuring serum transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and liver histology. Oxidative stress was quantified by measuring F2 isoprostane and glutathione levels. Leukocyte adhesion was assessed by intravital microscopy, and inflammatory cytokine response was assessed by measuring serum cytokine‐induced neutrophil chemoattractant‐1 (CINC‐1) levels. Bax and Bcl‐2 expression was measured by reverse transcription–polymerase chain reaction.

Results:  The model produced significant liver injury with elevated transaminases and an acute inflammatory response. Bucillamine reduced the liver injury, as indicated by reduced AST (932 ± 200.8 vs 2072.5 ± 511.79, P < 0.05). Bucillamine reduced Bax expression, serum CINC‐1 levels, and neutrophil adhesion, and upregulated Bcl‐2. However, bucillamine did not affect tissue glutathione levels nor the levels of oxidative stress, as measured by plasma and hepatic F2 isoprostane levels.

Conclusions:  Bucillamine reduces warm ischemia–reperfusion in the liver by inhibiting neutrophil activation and modulating Bax/Bcl‐2 expression.
Multi‐host ectomycorrhizal fungi are predominant in a Guinean tropical rainforest and shared between canopy trees and seedlings
Authors: Diédhiou Abdala Gamby , Selosse Marc‐André , Galiana Antoine , Diabaté Moussa , Dreyfus Bernard , Bâ Amadou Moustapha , De Faria Sergio Miana , Béna Gilles
Published: March 2010

The diversity of ectomycorrhizal (ECM) fungi on adult trees and seedlings of five species, Anthonotha fragrans, Anthonotha macrophylla, Cryptosepalum tetraphyllum, Paramacrolobium coeruleum and Uapaca esculenta, was determined in a tropical rain forest of Guinea. Ectomycorrhizae were sampled within a surface area of 1600 m2, and fungal taxa were identified by sequencing the rDNA Internal Transcribed Spacer region. Thirty‐nine ECM fungal taxa were determined, of which 19 multi‐hosts, 9 single‐hosts and 11 singletons. The multi‐host fungi represented 92% (89% when including the singletons in the analysis) of the total abundance. Except for A. fragrans, the adults of the host species displayed significant differentiation for their fungal communities, but their seedlings harboured a similar fungal community. These findings suggest that there was a potential for the formation of common mycorrhizal networks in close vicinity. However, no significant difference was detected for the δ13C and δ15N values between seedlings and adults of each ECM plant, and no ECM species exhibited signatures of mixotrophy. Our results revealed (i) variation in ECM fungal diversity according to the seedling versus adult development stage of trees and (ii) low host specificity of ECM fungi, and indicated that multi‐host fungi are more abundant than single‐host fungi in this forest stand.
An assessment of adverse effects of vildagliptin versus comparators on the liver, the pancreas, the immune system, the skin and in patients with impaired renal function from a large pooled database of Phase II and III clinical trials
Authors: Ligueros‐Saylan M. , Foley J. E. , Schweizer A. , Couturier A. , Kothny W.
Published: March 2010

Aim: To assess the safety of vildagliptin versus all comparators (ACs) with regard to organs, systems or tissues of particular interest in type 2 diabetes (T2DM) and areas of potential concern with dipeptidyl peptidase‐IV (DPP‐4) inhibitors.

Methods: Data were pooled from 38 studies where vildagliptin was given for ≥12 to > 104 weeks in patients with T2DM. Absolute and exposure‐adjusted incidence rates and Peto odds ratios (ORs) versus ACs with corresponding 95% confidence intervals (CI) were calculated.

Results: There were > 7000 subject‐years of exposure (SYE) to vildagliptin 50 mg bid and > 6500 SYE to ACs. For mild hepatic enzyme elevations with and without elevated bilirubin levels, the ORs for vildagliptin 50 mg bid were 1.24 (95% CI: [0.80, 1.93]) and 1.19 (95% CI: [0.29, 4.90]), respectively. The exposure‐adjusted incidences of markedly elevated hepatic enzymes and for enzyme elevations with bilirubin ≥ 2× ULN with vildagliptin 50 mg bid were ≤ those in the ACs group. For hepatic and pancreatitis‐related AEs, the ORs for vildagliptin 50 mg bid were 0.87 (95% CI: [0.64, 1.19]) and 0.70 (95% CI: [0.26, 1.88]), respectively, and for any AE in the infections and infestations SOC, this was 1.04 (95% CI: [0.96, 1.13]). The incidences of skin‐related AEs were low and the risk with vildagliptin 50 mg bid was not significantly different from ACs [(OR = 1.10 (95% CI: [0.80, 1.51])].

Conclusions: The present meta‐analyses indicate that vildagliptin was not associated with increased risk of hepatic events or hepatic enzyme elevations indicative of drug‐induced liver injury, pancreatitis, infections or skin‐related toxicity.
Assessing the cardio–cerebrovascular safety of vildagliptin: meta‐analysis of adjudicated events from a large Phase III type 2 diabetes population
Authors: Schweizer A. , Dejager S. , Foley J. E. , Couturier A. , Ligueros‐Saylan M. , Kothny W.
Published: March 2010

Aim: To assess the cardiovascular and cerebrovascular (CCV) safety of the dipeptidyl peptidase‐IV inhibitor vildagliptin.

Methods: Data were pooled from 25 Phase III studies of vildagliptin, used either as monotherapy or combination therapy, with durations of 12 weeks to ≥ 2 years. The safety of vildagliptin [50 mg qd (N = 1393) or 50 mg bid (N = 6116)] was assessed relative to a pool of all comparators [both placebo and active comparators (N = 6061)]. CCV events were adjudicated in a prospective, blinded fashion by an independent CCV adjudication committee. Meta‐analysis of confirmed CCV events was performed with Mantel–Haenszel risk ratios (RRs); categories included in the composite endpoint were acute coronary syndrome, transient ischaemic attack (with imaging evidence of infarction), stroke and CCV death. Subgroup analyses by age (< and ≥ 65 years), gender and cardiovascular (CV) risk status [high CV risk status defined as a previous history of events in the Standard MedDRA Queries of ischaemic heart disease, cardiac failure, ischaemic cerebrovascular conditions and/or embolic/thrombotic events, arterial) were also carried out. In addition, unadjusted and exposure‐adjusted incidences are presented for both the composite endpoint and its components.

Results: Relative to all comparators, the RRs for the composite endpoint were < 1 for both vildagliptin 50 mg qd [RR = 0.88; 95% CI (0.37, 2.11)] and vildagliptin 50 mg bid [RR = 0.84; 95% CI (0.62, 1.14)]. The results were consistent across subgroups defined by age, gender and CV risk status, including the higher CV risk subgroups of elderly patients [RR for vildagliptin 50 mg bid vs. all comparators = 1.04; 95% CI (0.62, 1.73)], males [RR = 0.87; 95% CI (0.60, 1.24)] or patients with a high CV risk status [RR = 0.78; 95% CI (0.51, 1.19)]. The exposure‐adjusted incidences of each component of the composite endpoint for vildagliptin 50 mg bid were also lower than or similar to those of all comparators.

Conclusions: In a large meta‐analysis, vildagliptin was not associated with an increased risk of adjudicated CCV events relative to all comparators in the broad population of type 2 diabetes including patients at increased risk of CCV events.
Effect of insulin glargine on glycaemic control and weight in obese and non‐obese people with type 2 diabetes: data from the AT.LANTUS trial
Authors: Khunti K. , Srinivasan B. T. , Shutler S. , Davies M. J.
Published: March 2010

Aims: To explore glucose lowering response to insulin initiation or switch to insulin glargine in obese and non‐obese individuals with type 2 diabetes mellitus (T2DM) and to examine weight gain and hypoglycaemic episodes in this group.

Methods:
Post hoc subgroup analysis using data of obese and non‐obese participants from a large multi‐centre (4555 participants with T2DM), multi‐national 24‐week randomized controlled trial of investigator titrated insulin glargine versus patient self‐managed titrated insulin glargine. This analysis was carried out to compare two subgroups: obese (≥30 kg/m2) and non‐obese (<30 kg/m2) participants.

Results: The mean body mass index (BMI) values were 33.7 kg/m2(n = 1833) and 25.9 kg/m2(n = 2755) in obese and non‐obese subjects, respectively. There was a significant reduction in glycated haemoglobin (HbA1c) from baseline in both subgroups but no significant difference between subgroups (1.15 vs. 1.15%, p = 0.50). Overall, there was a 1.21 kg (s.d. 3.3) increase in weight in individuals who were non‐obese and a 1.08 kg (s.d. 3.9) increase in obese individuals (p = 0.67). There was no significant difference in the proportion of participants achieving an HbA1c of <7.0% at 6 months in both the subgroups (28.8 vs. 27.1%, p = 0.20). In multiple logistic regression, BMI was not a prognostic factor in achieving a target of HbA1c ≤ 7.0%. There was no significant difference in severe hypoglycaemic episodes between obese and non‐obese subgroups (1.3 vs. 1.0%); however, significantly more non‐obese individuals experienced nocturnal hypoglycaemic episodes(4.5 vs. 2.4%, p < 0.05).

Conclusions: In this study, treatment with insulin glargine in people with T2DM was associated with a significant reduction in HbA1c without differential increase in weight gain in obese and non‐obese subgroups. Rates of severe hypoglycaemia were not different between obese and non‐obese subgroups.