bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial Ubiquitin Ligase MITOL Ubiquitinates Mutant SOD1 and Attenuates Mutant SOD1-induced Reactive Oxygen Species Generation
Authors: Yonashiro Ryo , Sugiura Ayumu , Miyachi Misako , Fukuda Toshifumi , Matsushita Nobuko , Inatome Ryoko , Ogata Yoshinobu , Suzuki Takehiro , Dohmae Naoshi , Yanagi Shigeru
Published: September 2009

We have previously identified a novel mitochondrial ubiquitin ligase, MITOL, which is localized in the mitochondrial outer membrane and is involved in the control of mitochondrial dynamics. In this study, we examined whether MITOL eliminates misfolded proteins localized to mitochondria. Mutant superoxide dismutase1 (mSOD1), one of misfolded proteins, has been shown to localize in mitochondria and induce mitochondrial dysfunction, possibly involving in the onset and progression of amyotrophic lateral sclerosis. We found that in the mitochondria, MITOL interacted with and ubiquitinated mSOD1 but not wild-type SOD1. In vitro ubiquitination assay revealed that MITOL directly ubiquitinates mSOD1. Cycloheximide-chase assay in the Neuro2a cells indicated that MITOL overexpression promoted mSOD1 degradation and suppressed both the mitochondrial accumulation of mSOD1 and mSOD1-induced reactive oxygen species (ROS) generation. Conversely, the overexpression of MITOL CS mutant and MITOL knockdown by specific siRNAs resulted in increased accumulation of mSOD1 in mitochondria, which enhanced mSOD1-induced ROS generation and cell death. Thus, our findings indicate that MITOL plays a protective role against mitochondrial dysfunction caused by the mitochondrial accumulation of mSOD1 via the ubiquitin–proteasome pathway.
TagDust—a program to eliminate artifacts from next generation sequencing data
Authors: Lassmann Timo , Hayashizaki Yoshihide , Daub Carsten O.
Published: September 2009

Motivation: Next-generation parallel sequencing technologies produce large quantities of short sequence reads. Due to experimental procedures various types of artifacts are commonly sequenced alongside the targeted RNA or DNA sequences. Identification of such artifacts is important during the development of novel sequencing assays and for the downstream analysis of the sequenced libraries.

Results: Here we present TagDust, a program identifying artifactual sequences in large sequencing runs. Given a user-defined cutoff for the false discovery rate, TagDust identifies all reads explainable by combinations and partial matches to known sequences used during library preparation. We demonstrate the quality of our method on sequencing runs performed on Illumina's Genome Analyzer platform.

Availability: Executables and documentation are available from http://genome.gsc.riken.jp/osc/english/software/.

Contact:  timolassmann@gmail.com
A Systematic Review of Single Chinese Herbs for Alzheimer′s Disease Treatment
Authors: Fu Li-Min , Li Ju-Tzu
Published: September 2009

The objectives here are to provide a systematic review of the current evidence concerning the use of Chinese herbs in the treatment of Alzheimer′s disease (AD) and to understand their mechanisms of action with respect to the pathophysiology of the disease. AD, characterized microscopically by deposition of amyloid plaques and formation of neurofibrillary tangles in the brain, has become the most common cause of senile dementia. The limitations of western medications have led us to explore herbal medicine. In particular, many Chinese herbs have demonstrated some interesting therapeutic properties. The following databases were searched from their inception: MEDLINE (PUBMED), ALT HEALTH WATCH (EBSCO), CINAH and Cochrane Central. Only single Chinese herbs are included. Two reviewers independently extracted the data and performed quality assessment. The quality assessment of a clinical trial is based on the Jadad criteria. Seven Chinese herbs and six randomized controlled clinical trials were identified under the predefined criteria. Ginkgo biloba, Huperzine A (Lycopodium serratum) and Ginseng have been assessed for their clinical efficacy with limited favorable evidence. No serious adverse events were reported. Chinese herbs show promise in the treatment of AD in terms of their cognitive benefits and more importantly, their mechanisms of action that deal with the fundamental pathophysiology of the disease. However, the current evidence in support of their use is inconclusive or inadequate. Future research should place emphasis on herbs that can treat the root of the disease.
Elevated serum uric acid levels following heart transplantation predict all‐cause and cardiac mortality
Authors: Arora Satish , Aukrust Pål , Ueland Thor , Broch Kaspar , Simonsen Svein , Gude Einar , Fiane Arnt E. , Geiran Odd , Wergeland Ragnhild , Andreassen Arne K. , Gullestad Lars
Published: September 2009

Aims

We evaluated the relationship between elevated serum uric acid (SUA) and mortality as well as cardiac allograft vasculopathy (CAV) among 184 heart transplant (HTx) recipients. We also measured inflammatory, neurohormonal, and oxidative stress markers to explore pathophysiological mechanisms.

Methods and results

There were 28 (15%) deaths, patients with SUA ≥502 µmol/L (upper quartile) at 1 year post‐HTx had an increased risk of total mortality (adjusted HR 2.21, P = 0.03) and cardiac mortality (adjusted HR 4.38, P = 0.03). Elevated SUA was a significant risk factor for development of moderate/severe angiographic CAV (adjusted HR 4.79, P = 0.01). A smaller decline in SUA (<97 µmol/L) during the first year post‐HTx was also associated with an increased risk of mortality (P = 0.02). Patients with elevated SUA had significantly higher levels of high‐sensitivity C‐reactive protein (P = 0.008) and N‐terminal probrain natriuretic peptide (P = 0.022), but there was no significant difference in oxidative stress parameters.

Conclusion

Elevated SUA at 1 year post‐HTx, or a modest rather than a marked decline in SUA levels during the first year post‐HTx, is associated with an increased risk of mortality. Although the pathophysiological mechanism is unclear, our data indicate a potential relationship between SUA and inflammation which should be explored further.
Residual Activity of Fludioxonil and Pyrimethanil Against Penicillium expansum on Apple Fruit
Authors: Xiao C. L. , Boal R. J.
Published: September 2009

Blue mold caused by Penicillium expansum is a major postharvest disease of apples (Malus × domestica). Residual activity of fludioxonil and pyrimethanil in apple fruit against P. expansum was investigated during 2005 to 2008. Fruit of the cultivar Delicious harvested from commercial orchards where fungicides were not used were either not treated or drenched with fludioxonil, pyrimethanil, or thiabendazole prior to storage and then stored in controlled atmosphere at 0°C for 5 or 7 months, after which time the fruit were removed from storage and subjected to washing and brushing, practices that are done at the time of packing. Fruit were then wounded and inoculated with conidial suspensions of P. expansum. Inoculated fruit were treated with either sterile water or fungicides. Fruit were stored at 0°C for 8 weeks and at room temperature for one additional week after cold storage. To determine distribution of fungicide residues in the fruit flesh, fruit were cut horizontally at the equator, sprayed with the conidial suspension of P. expansum, incubated at room temperature, and examined for inhibition of blue mold on the cut fruit 4 days after inoculation. Fungicide residues on/in the fruit were analyzed using a gas chromatograph. Zero to 26% blue mold incidence was observed on fludioxonil-drenched fruit that were inoculated and not treated with fungicides at packing. No decay or <4% blue mold incidence was observed on pyrimethanil-drenched fruit that were inoculated and not treated with fungicides at packing, whereas 65 to 99% blue mold incidence was observed on thiabendazole-drenched fruit that were not treated with fungicides at packing. An average of >32 mm inhibition zone and approximately 5 mm inhibition zone measured from the fruit peel toward the fruit core were observed on pyrimethanil-drenched and fludioxonil-drenched fruit, respectively. Washing and brushing at the time of packing 5 and 7 months after harvest did not remove or only partially removed residues of fludioxonil and pyrimethanil from apple fruit. The results suggest that residues of fludioxonil and pyrimethanil on/in apple fruit are persistent and that residual protection of apple fruit by the two fungicides can last for at least 7 months under apple-storage conditions.
Antifungal Activity of Silver Ions and Nanoparticles on Phytopathogenic Fungi
Authors: Jo Young-Ki , Kim Byung H. , Jung Geunhwa
Published: September 2009

Silver in ionic or nanoparticle forms has a high antimicrobial activity and is therefore widely used for various sterilization purposes including materials of medical devices and water sanitization. There have been relatively few studies on the applicability of silver to control plant diseases. Various forms of silver ions and nanoparticles were tested in the current study to examine the antifungal activity on two plant-pathogenic fungi, Bipolaris sorokiniana and Magnaporthe grisea. In vitro petri dish assays indicated that silver ions and nanoparticles had a significant effect on the colony formation of these two pathogens. Effective concentrations of the silver compounds inhibiting colony formation by 50% (EC50) were higher for B. sorokiniana than for M. grisea. The inhibitory effect on colony formation significantly diminished after silver cations were neutralized with chloride ions. Growth chamber inoculation assays further confirmed that both ionic and nanoparticle silver significantly reduced these two fungal diseases on perennial ryegrass (Lolium perenne). Particularly, silver ions and nanoparticles effectively reduced disease severity with an application at 3 h before spore inoculation, but their efficacy significantly diminished when applied at 24 h after inoculation. The in vitro and in planta evaluations of silver indicated that both silver ions and nanoparticles influence colony formation of spores and disease progress of plant-pathogenic fungi. In planta efficacy of silver ions and nanoparticles is much greater with preventative application, which may promote the direct contact of silver with spores and germ tubes, and inhibit their viability.
Influence of Monocropping Brown Stem Rot–Resistant and –Susceptible Soybean Accessions on Soil and Stem Populations of Phialophora gregata f. sp. sojae
Authors: Hughes T. J. , Koval N. C. , Esker P. D. , Grau C. R.
Published: September 2009

Brown stem rot (BSR)-resistant and -susceptible soybean accessions were continuously cropped in an area never previously seeded to soybean to study the influence of monocultures on soil and stem populations of Phialophora gregata f. sp. sojae. P. gregata f. sp. sojae population size and genotype composition were determined by dilution plating, isolation of P. gregata f. sp. sojae and standard polymerase chain reaction (PCR), and by quantitative real-time PCR (q-PCR. In general, the sizes of P. gregata f. sp. sojae populations in soil were similar regardless of monoculture. The percentage of P. gregata f. sp. sojae genotype B was greater than A in soil following the monoculture of both BSR-susceptible and -resistant soybean accessions. Following the monoculture of a BSR-resistant accession, the percentage of P. gregata f. sp. sojae genotype B was greater than A. Overall, P. gregata f. sp. sojae populations in stems of a BSR-susceptible accession were greater than those in stems of a BSR-resistant accession. P. gregata f. sp. sojae genotype B was detected more often than A in stems of both resistant and susceptible accessions planted following a BSR-resistant monoculture. P. gregata f. sp. sojae genotype B was also detected more often than A in stems of a BSR-resistant accession planted following a BSR-susceptible monoculture. P. gregata f. sp. sojae genotypes A and B were isolated at similar frequencies from stems of a BSR-susceptible accession planted following a BSR-susceptible monoculture. However, q-PCR results indicate that the percentage of P. gregata f. sp. sojae genotype A was greater than B in stems of a BSR-susceptible accession planted following a BSR-susceptible monoculture. Among BSR-susceptible accessions, those with the soybean cyst nematode (SCN)-resistant cv. Peking in their parentage had the largest populations of P. gregata f. sp. sojae and a greater percentage of P. gregata f. sp. sojae genotype B. Similar results were observed for BSR-resistant accessions derived from SCN-resistant PI 88788.
Biological and Molecular Characterization of the Cucurbit aphid-borne yellows virus Affecting Cucurbits in Tunisia
Authors: Mnari-Hattab M. , Gauthier N. , Zouba A.
Published: September 2009

Surveys of yellowing viruses under nonheated and geothermal heated plastic tunnels and in open field crops of melon (Cucumis melo), cucumber (C. sativus), zucchini (Cucurbita pepo), squash (C. maxima), watermelon (Citrullus lanatus), and ware cucurbit (Ecballium elaterium) were carried out year-round during 2000–2001, 2003, and 2004 in the major cucurbit-growing areas in Tunisia. Severe yellowing symptoms on older leaves of cucurbits were observed in open fields and under plastic-tunnel production systems. These yellowing symptoms and large populations of aphids (Aphis gossypii) on a diversity of cucurbit crops in Tunisia support the hypothesis of a viral cause of the disease. Virus identification using double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA), followed by reverse transcription–polymerase chain reaction (RT-PCR) and immunocapture (IC)-RT-PCR showed that Cucurbit aphid-borne yellows virus (CABYV) was largely distributed in melon, cucumber, zucchini, squash, and watermelon crops. Ware cucurbit (E. elaterium) and lettuce (Lactuca sativa) crops were identified as potential CABYV reservoirs. The RT-PCR-amplified partial coat protein (CP) and P4 genes were cloned and sequenced from nine Tunisian CABYV isolates. CP and P4 gene nucleotide and amino acid sequence comparisons as well as phylogenetic reconstructions showed that the Tunisian isolates clustered into two major subgroups. Comparisons with CABYV sequences retrieved from GenBank showed high nucleotide and CP amino acid identities, and close relationships of the Tunisian isolates with Italian and French isolates.
First Report of Cherry green ring mottle virus in Plum (Prunus domestica) in North America
Authors: Wang L. P. , Hong N. , Wang G. P. , Michelutti R. , Zhang B. L.
Published: September 2009

Cherry green ring mottle virus (CGRMV), a member of the genus Foveavirus, is reported to infect several Prunus species including sour cherry (Prunus cerasus L.), sweet cherry (P. avium L.), flowering cherry (P. serrulata L.), peach (P. persica B.), and apricot (P. armeniaca L.). The virus has been detected in most regions of North America, Europe, New Zealand, Africa, and Japan where Prunus species are grown for production (3). In sour cherry, the virus causes leaf yellowing and dark mottle around secondary veins. Other Prunus species are usually symptomless hosts of CGRMV. There is no report on the infection of CGRMV in plum so far. A survey was conducted to evaluate the sanitary status of stone fruit tree collections in the Canadian Clonal Genebank (CCG) at the Greenhouse and Processing Crops Research Center (GPCRC) in Harrow, Ontario (Canada). In October 2006, samples from 110 cultivar clones including 28 sweet cherry, 36 sour cherry, 12 hybrids, and 34 plum accessions, were bud grafted onto indicator seedlings of P. serrulata ‘Kwanzan’ for virus indexing in a greenhouse with a controlled environment. In April 2007, symptoms of epinasty and/or rusty necrotic fragments of midrib, which is indicative of Kwanzan infection by CGRMV (4), were observed on indicator plants inoculated with samples from eight clones (one sweet cherry, one cherry plum (P. besseyi × P. hortulana) and six plum). Indicator plants inoculated with samples from 19 other clones (three sweet cherry, nine sour cherry, one cherry plum and six plum) showed symptoms including small leaves and leaves that were twisted, deformed, bubbled, and/or had shot holes. Total RNA was extracted from leaves of all these symptomatic indicator plants by the cetyltrimethylammoniumbromide (CTAB) method (2). One-step reverse transcription (RT)-PCR was carried out using the primer set CGRMV1 (CCTCATTCACATAGCTTAGGTTT, 7,297 to 7,313 bp) and CGRMV2 (ACTTTAGCTTCGCCCCGTG, 8,245 to 8,227 bp) (1) for the detection of CGRMV. Amplicons of the expected size of 948 bp were consistently produced from eight samples showing symptoms of CGRMV infection, no amplicons were produced from the other 19 samples. Those results were further confirmed by RT-PCR detection for the original field samples. The fragment from plum cv. Vanier was cloned into pGEM-T Easy and sequenced in both directions of three clones. The resulting nucleotide sequence (GenBank Accession No. FJ402843) had the highest identity (97%) with that of a CGRMV isolate Star from sweet cherry (GenBank Accession No. AY841279) and had lower identity (81%) with that of a CGRMV isolate from apricot (GenBank Accession No. AY172334.1). To our knowledge, this is the first report of CGRMV infecting plum in North America.

References: (1) R. Li and R. Mock. J. Virol. Methods 129:162, 2005. (2) R. Li et al. Plant Dis. 88:12, 2004. (3) K. G. Parker et al. USDA Agric. Handb. No. 437:193, 1976. (4) Y. Zhang et al. J. Gen. Virol. 79:2275, 1998.
Quantifying Effects of Seedborne Inoculum on Virus Spread, Yield Losses, and Seed Infection in the Pea seed-borne mosaic virus–Field Pea Pathosystem
Authors: Coutts B. A. , Prince R. T. , Jones R. A. C.
Published: September 2009

Field experiments examined the effects of sowing field pea seed with different amounts of infection with Pea seed-borne mosaic virus (PSbMV) on virus spread, seed yield, and infection levels in harvested seed. Plots were sown with seed with actual or simulated seed transmission rates of 0.3 to 6.5% (2005) or 0.1 to 8% (2006), and spread was by naturally occurring migrant aphids. Plants with symptoms and incidence increased with the amount of primary inoculum present. When final incidence reached 97 to 98% (2005) and 36% (2006) in plots sown with 6.5 to 8% infected seed, yield losses of 18 to 25% (2005) and 13% (2006) resulted. When incidence reached 48 to 76% in plots sown with 1.1-2 to 2% initial infection, seed yield losses were 15 to 21% (2005). Diminished seed weight and seed number both contributed to the yield losses. When the 2005 data for the relationships between percent incidence and yield or yield gaps were plotted, 81 to 84% of the variation was explained by final incidence and, for each 1% increase, there was a yield decline of 7.7 to 8.2 kg/ha. Seed transmission rates in harvested seed were mostly greater than those in the seed sown when climatic conditions favored early virus spread (1 to 17% in 2005) but smaller when they did not (0.2 to 2% in 2006). In 2007, sowing infected seed at high seeding rate with straw mulch and regular insecticide application resulted in slower spread and smaller seed infection than sowing at standard seeding rate without straw mulch or insecticide. When data for the relationship between final percent incidence and seed transmission in harvested seed were plotted (all experiments), 95 to 99% of the variation was explained by PSbMV incidence. A threshold value of <0.5% seed infection was established for sowing in high-risk zones.
Demonstration of Pathotype Specificity in Stem Rust of Perennial Ryegrass
Authors: Pfender W.
Published: September 2009

Rust diseases cause significant damage in forage and seed crops of perennial ryegrass (Lolium perenne), which is highly heterozygous and heterogeneous and thus presents difficulty in genetic analysis. There has been no definitive demonstration of the existence of pathotypes for stem rust or other rusts of perennial ryegrass, although experiments with crown rust (Puccinia coronata) of this host are strongly suggestive of pathotype specificity. We made single-pustule isolates of P. graminis subsp. graminicola, and applied them individually to a set of genetically diverse, clonally propagated individuals of L. perenne. There were clear examples of different patterns of virulence among isolates across the different plant clones, including qualitative and quantitative differences in resistance. These data demonstrate the existence of pathotype specificity in stem rust of L. perenne, information which will be useful in breeding for disease resistance.
Molecular Mapping of a Stripe Rust Resistance Gene in Spring Wheat Cultivar Zak
Authors: Sui X. X. , Wang M. N. , Chen X. M.
Published: September 2009

Stripe rust (yellow rust), caused by Puccinia striiformis f. sp. tritici, is one of the most devastating foliar diseases of wheat (Triticum aestivum) worldwide. Growing resistant cultivars is the best approach for control of the disease. Although the stripe rust resistance in spring wheat cv. Zak has been circumvented by a group of races of the pathogen predominant in the United States since 2000, the resistance genes in Zak were unknown. To identify and map the genes for resistance to stripe rust, Zak was crossed with susceptible wheat genotype ‘Avocet Susceptible’. Seedlings of the parents and F1, F2, and F3progeny were tested with P. striiformis f. sp. tritici races PST-43 and PST-45 under controlled greenhouse conditions. Genetic analysis determined that Zak has a single dominant gene, designated as YrZak, conferring race-specific all-stage resistance. Resistance gene analog polymorphism (RGAP), simple sequence repeat (SSR), and sequence-tagged site (STS) techniques were used to identify molecular markers linked to YrZak. A linkage group of three RGAP, three SSR, and three STS markers was constructed for YrZak using 205 F3lines. Amplification of the complete set of Chinese Spring nulli-tetrasomic lines with RGAP marker Xwgp102 indicated that YrZak is present on chromosome 2B. The three SSR markers further mapped YrZak to the long arm of chromosome 2B. Amplification of chromosome 2B deletion lines with SSR marker Xgwm501 further confirmed that YrZak is on chromosome 2BL. To determine the genetic distance between YrZak and Yr5, which also is present on chromosome 2BL, 300 F2plants from cross Zak/Yr5 were tested with PST-43. Six susceptible plants were identified from the F2population, indicating that YrZak and Yr5 are ≈42 centimorgans apart. The results of race reactions and chromosomal locations indicated that YrZak is different from previously identified genes for resistance to stripe rust. This gene should be useful in monitoring virulence changes in the pathogen population and in studying host–pathogen interactions.
The STRUCTURAL MAINTENANCE OF CHROMOSOMES 5/6 Complex Promotes Sister Chromatid Alignment and Homologous Recombination after DNA Damage inArabidopsis thaliana
Authors: Watanabe Koichi , Pacher Michael , Dukowic Stefanie , Schubert Veit , Puchta Holger , Schubert Ingo
Published: September 2009

Sister chromatids are often arranged as incompletely aligned entities in interphase nuclei of Arabidopsis thaliana. The STRUCTURAL MAINTENANCE OF CHROMOSOMES (SMC) 5/6 complex, together with cohesin, is involved in double-strand break (DSB) repair by sister chromatid recombination in yeasts and mammals. Here, we analyzed the function of genes in Arabidopsis. The wild-type allele of SMC5 is essential for seed development. Each of the two SMC6 homologs of Arabidopsis is required for efficient repair of DNA breakage via intermolecular homologous recombination in somatic cells. Alignment of sister chromatids is enhanced transiently after X-irradiation (and mitomycin C treatment) in wild-type nuclei. In the smc5/6 mutants, the x-ray–mediated increase in sister chromatid alignment is much lower and delayed. The reduced S phase–established cohesion caused by a knockout mutation in one of the α-kleisin genes, SYN1, also perturbed enhancement of sister chromatid alignment after irradiation, suggesting that the S phase–established cohesion is a prerequisite for correct DSB-dependent cohesion. The radiation-sensitive51 mutant, deficient in heteroduplex formation during DSB repair, showed wild-type frequencies of sister chromatid alignment after X-irradiation, implying that the irradiation-mediated increase in sister chromatid alignment is a prerequisite for, rather than a consequence of, DNA strand exchange between sister chromatids. Our results suggest that the SMC5/6 complex promotes sister chromatid cohesion after DNA breakage and facilitates homologous recombination between sister chromatids.
Dynamic Plastid Redox Signals Integrate Gene Expression and Metabolism to Induce Distinct Metabolic States in Photosynthetic Acclimation inArabidopsis
Authors: Bräutigam Katharina , Dietzel Lars , Kleine Tatjana , Ströher Elke , Wormuth Dennis , Dietz Karl-Josef , Radke Dörte , Wirtz Markus , Hell Rüdiger , Dörmann Peter , Nunes-Nesi Adriano , Schauer Nicolas , Fernie Alisdair R. , Oliver Sandra N. , Geigenberger Peter , Leister Dario , Pfannschmidt Thomas
Published: September 2009

Plants possess acclimation responses in which structural reconfigurations adapt the photosynthetic apparatus to fluctuating illumination. Long-term acclimation involves changes in plastid and nuclear gene expression and is controlled by redox signals from photosynthesis. The kinetics of these signals and the adjustments of energetic and metabolic demands to the changes in the photosynthetic apparatus are currently poorly understood. Using a redox signaling system that preferentially excites either photosystem I or II, we measured the time-dependent impact of redox signals on the transcriptome and metabolome of Arabidopsis thaliana. We observed rapid and dynamic changes in nuclear transcript accumulation resulting in differential and specific expression patterns for genes associated with photosynthesis and metabolism. Metabolite pools also exhibited dynamic changes and indicate readjustments between distinct metabolic states depending on the respective illumination. These states reflect reallocation of energy resources in a defined and reversible manner, indicating that structural changes in the photosynthetic apparatus during long-term acclimation are additionally supported at the level of metabolism. We propose that photosynthesis can act as an environmental sensor, producing retrograde redox signals that trigger two parallel adjustment loops that coordinate photosynthesis and metabolism to adapt plant primary productivity to the environment.
Compact Modeling of the Temperature Dependence of Parasitic Resistances in SiGe HBTs Down to 30 K
Authors: Luo Lan , Niu Guofu , Moen Kurt A. , Cressler John D.
Published: September 2009

In this paper, we investigate the physics and modeling of temperature dependence of various parasitic resistances in SiGe heterojunction bipolar transistors down to 30 K. Carrier freezeout is shown to be the dominant contributor to increased resistances at cryogenic temperatures for lightly-doped and moderately-doped regions, whereas the temperature dependence of the mobility is the dominant contributor to the temperature dependence of heavily-doped regions. Two incomplete ionization models, the classic model with a doping dependent activation energy and the recent model of Altermatt , are shown to underestimate and overestimate incomplete ionization rate below 100 K for intrinsic base doping, respectively. Analysis of experimental data shows that the bound state fraction factor is temperature dependent and including this temperature dependence enables compact modeling of resistances from 30 to 300 K for moderately-doped regions. For heavily-doped regions, a dual power law mobility approximation with complete ionization is shown to work well down to 30 K. An alternative approach is also presented for heavily-doped resistors which allows one to use the same model equation for all regions.
The effects of hormonal contraceptives on bone turnover markers and bone health
Authors: Herrmann Markus , Seibel Markus J.
Published: September 2009

Sex hormones are important regulators of bone metabolism. As hormonal contraceptives contain either oestrogens or progestins, or a combination thereof, it is conceivable that these widely used agents have an effect on bone metabolism and bone health. The main users of hormonal contraceptives, adolescent girls and young women, are still building bone and accruing bone mass and may therefore be particularly susceptible to the effects of hormonal contraceptives on bone. Despite these concerns, the effects of hormonal contraceptives on bone health are still poorly understood. As biochemical markers of bone turnover have been proven useful tools in the assessment and monitoring of bone metabolism, we reviewed the effects of combined and gestagen‐only hormonal contraceptives on bone turnover markers and related effects on bone mineral density and fracture risk in premenopausal women, as documented in the literature until January 2009.
Evaluation of accuracy of fine needle aspiration cytology in BI‐RADS3 category breast lesions: cytohistological correlation in 337 cases
Authors: Engohan‐Aloghe C. , Hottat N. , Cosaert J. , Boutemy R. , Fayt I. , Noël J.‐C.
Published: September 2009

C. Engohan‐Aloghe, N. Hottat, J. Cosaert, R. Boutemy, I. Fayt and J.‐C. Noël Evaluation of accuracy of fine needle aspiration cytology in BI‐RADS3 category breast lesions: cytohistological correlation in 337 cases

Objective:  To evaluate the accuracy of fine needle aspiration cytology (FNAC) in BI‐RADS3 breast lesions.

Methods:  Between January 2004 and December 2007, 337 cases from BI‐RADS3 lesions underwent FNAC. Three to six needle passes were made on each patient. In 67 cases (20%) a histological biopsy was performed. Cytological and histological interpretations were performed by the same pathologist.

Results:  The histological diagnosis showed that 88% (59/67) of BI‐RADS3 breast lesions were benign. Only 6% (4/67) were malignant, consisting of ductal carcinoma in situ and infiltrating ductal carcinoma.

Conclusion:  BI‐RADS3 lesions remain disruptive in their management. However, the correlation between cytology and histology showed that most of these lesions were benign and that finally FNAC remains a useful and accurate test in the management of these lesions.
Immunosuppression and atypical infections in CML patients treated with dasatinib at 140 mg daily
Authors: Sillaber C. , Herrmann H. , Bennett K. , Rix U. , Baumgartner C. , Böhm A. , Herndlhofer S. , Tschachler E. , Superti‐Furga G. , Jäger U. , Valent P.
Published: September 2009

Background  The multikinase inhibitor dasatinib exerts growth‐inhibitory effects in patients with imatinib‐resistant chronic myeloid leukaemia (CML). In first clinical trials, side effects of dasatinib, 140 mg daily, were reported to be mild and tolerable.

Patients and methods  We examined the side effect profile in 16 patients with imatinib‐resistant CML who received 140 mg dasatinib daily in our center.

Results  Dasatinib produced substantial and sometimes severe or even life‐threatening side effects with ≥ 10% body weight loss (6/16 patients), pleural effusions grade II or higher (12/16) and infectious complications (12/16), including atypical infections not seen in imatinib‐treated patients. One patient developed Epstein–Barr‐Virus‐positive mucosal leucoplakia, one died from pneumonia caused by pneumocystis carinii and three patients developed a skin‐cancer. Most events were recorded within the first 2 years of therapy, only skin tumours developed after the second year. In ex vivo experiments performed in dasatinib‐treated patients, transient suppression of IgE‐dependent activation of blood basophils and TcR‐dependent activation of T‐lymphocytes was found. Moreover, in drug‐binding studies, dasatinib was found to bind to several key kinase‐targets of the immune system including Lyn and Btk, in mast cell, basophil, B‐cell and T‐cell lines.

Conclusion  Dasatinib acts not only anti‐neoplastic in CML but may also act as an immunosuppressive agent when applied at 140 mg daily, and produces frequent pleural effusions and weight loss in advanced CML.
CDKs as therapeutic targets for the human genetic disease tuberous sclerosis?
Authors: Rosner M. , Dolznig H. , Fuchs C. , Siegel N. , Valli A. , Hengstschläger M.
Published: September 2009

The tuberous sclerosis gene 2 product tuberin is an important regulator of the mammalian target of rapamycin (mTOR). In addition, tuberin is known to bind to the cyclin‐dependent kinase (CDK) inhibitor p27Kip1 (p27) and to regulate its stability and localization via mTOR‐independent mechanisms. Recently, evidence has been provided that tuberin also affects p27 localization via regulating mTOR′s potential to activate the serum‐ and glucocorticoid‐inducible kinase (SGK1) to phosphorylate p27. Taken together, these findings strengthen the argument that besides mTOR‐inhibitors, such as rapamycin analogues, p27 and CDKs could also be considered targets for hamartoma therapeutics in tuberous sclerosis.
Effects of vegetation state on biodiversity and nitrogen retention in created wetlands: a test of the biodiversity–ecosystem functioning hypothesis
Authors: WEISNER STEFAN E. B. , THIERE GERALDINE
Published: September 2009

1. Nitrogen retention in wetlands provides an example of an ecosystem function that is desired by human society, and is a rationale for the creation of wetlands to decrease nitrogen fluxes from nitrate‐loaded river catchments to coastal waters.

2. Here, we tested the impact of different vegetation states on species diversity and nitrogen retention during 4 years in surface‐flow wetlands receiving nitrate‐rich water. Tall emergent vegetation or submerged vegetation was introduced to six experimental wetlands each and six wetlands were left as unplanted controls for free development of vegetation. This resulted in three vegetation states dominated by emergent vegetation, by a mixture of submerged vegetation and filamentous green algae or by filamentous green algae.

3. Species diversity (species richness and Shannon diversity) of plants was initially lowest in free development wetlands, but during the study became lower in the emergent vegetation wetlands than in the other wetlands. Diversity of macroinvertebrates was initially lower in the submerged vegetation wetlands than in the other wetlands, but this difference disappeared during the study. Nitrogen retention was consistently higher in emergent vegetation wetlands than in the other wetlands throughout the study.

4. We conclude that plant diversity in wetlands dominated by tall emergent vegetation gradually became lower than in other wetlands, due to dominant species competitively excluding other plants. However, these wetlands were more efficient at removing nitrogen than those dominated by filamentous algae or submerged macrophytes.

5. Management of wetlands often aims to decrease the dominance of tall emergent vegetation for the benefit of plant species diversity and habitat heterogeneity. Our results demonstrate a biodiversity benefit, but also show that this strategy may decrease the ability of wetlands to remove nitrogen. In this case, there is no support for the hypothesis that biodiversity enhances ecosystem function.
Classification of natural flow regimes in Australia to support environmental flow management
Authors: KENNARD MARK J. , PUSEY BRADLEY J. , OLDEN JULIAN D. , MACKAY STEPHEN J. , STEIN JANET L. , MARSH NICK
Published: September 2009

1. The importance of hydrologic variability for shaping the biophysical attributes and functioning of riverine ecosystems is well recognised by ecologists and water resource managers. In addition to the ecological dependences of flow for aquatic organisms, human societies modify natural flow regimes to provide dependable ecological services, including water supply, hydropower generation, flood control, recreation and navigation. Management of scarce water resources needs to be based on sound science that supports the development of environmental flow standards at the regional scale.

2. Hydrological classification has long played an essential role in the ecological sciences for understanding geographic patterns of riverine flow variability and exploring its influence on biological communities, and more recently, has been identified as a critical process in environmental flow assessments.

3. We present the first continental‐scale classification of hydrologic regimes for Australia based on 120 metrics describing ecologically relevant characteristics of the natural hydrologic regime derived from discharge data for 830 stream gauges. Metrics were calculated from continuous time series (15–30 years of record constrained within a 36‐year period) of mean daily discharge data, and classification was undertaken using a fuzzy partitional method – Bayesian mixture modelling.

4. The analysis resulted in the most likely classification having 12 classes of distinctive flow‐regime types differing in the seasonal pattern of discharge, degree of flow permanence (i.e. perennial versus varying degrees of intermittency), variations in flood magnitude and frequency and other aspects of flow predictability and variability. Geographic, climatic and some catchment topographic factors were generally strong discriminators of flow‐regime classes. The geographical distribution of flow‐regime classes showed varying degrees of spatial cohesion, with stream gauges from certain flow‐regime classes often being non‐contiguously distributed across the continent. These results support the view that spatial variation in hydrology is determined by interactions among climate, geology, topography and vegetation at multiple spatial and temporal scales. Decision trees were also developed to provide the ability to determine the natural flow‐regime class membership of new stream gauges based on their key environmental and/or hydrological characteristics.

5. The need to recognise hydrologic variation at multiple spatial scales is an important first step to setting regional‐scale environmental flow management strategies. We expect that the classification produced here can underpin the development of a greater understanding of flow‐ecology relationships in Australia, and management efforts aimed at prescribing environmental flows for riverine restoration and conservation.
Alpine headwater streams as reservoirs of remnant populations of the Danubian clade of brown trout
Authors: BARIC SANJA , RIEDL ANDREAS , MERANER ANDREAS , MEDGYESY NIKOLAUS , LACKNER REINHARD , PELSTER BERND , VIA JOSEF DALLA
Published: September 2009

1. The watercourses of Austria are mainly part of the Danube drainage system. Nonetheless, only few brown trout (Salmo trutta) populations of the Danubian phylogenetic lineage have been found in this region, not being introgressed by hatchery‐reared fish of the allochthonous Atlantic lineage. The present study was aimed at identifying further waterbodies that might harbour the non‐admixed gene pool of the Danubian clade trout.

2. In a first step, the complete mitochondrial DNA control region of 447 specimens from 20 sampling sites was sequenced to screen for the presence of specific haplotypes. In a second step, 332 individuals from 15 populations were analysed at 10 microsatellite DNA loci.

3. Although sampling concentrated on remote Alpine headwater streams, introgression of hatchery strains was more common than expected from existing stocking records. For seven populations, however, no evidence of recent hatchery trout introgression was found and it is suggested that they might represent the indigenous gene pool.

4. Populations showing no evidence of hatchery introgression displayed lower levels of intrapopulation variability and higher degrees of differentiation compared to purported admixed populations.

5. Our study demonstrates the necessity of combining different molecular markers to reveal the impact of introgression into wild populations, since at some sampling sites admixture would have remained undetected if only a single molecular technique was applied.

6. The identification and characterisation of non‐introgressed populations provides important information for setting conservation priorities and preventing further loss of genetic integrity of a unique element of the native fish fauna.
Changes in cell migration‐related molecules expressed by thymic microenvironment during experimental Plasmodium berghei infection: consequences on thymocyte development
Authors: Gameiro Jacy , Nagib Patrícia R. A. , Andrade Carolina F. , Villa‐Verde Déa M. S. , Silva‐Barbosa Suse D. , Savino Wilson , Costa Fábio T. M. , Verinaud Liana
Published: September 2009

We previously showed alterations in the thymus during experimental infection with Plasmodium berghei. Such alterations comprised histological changes, with loss of cortical–medullary limits, and the intrathymic presence of parasites. As the combination of chemokines, adhesion molecules and extracellular matrix (ECM) is critical to appropriate thymocyte development, we analysed the thymic expression of ECM ligands and receptors, as well as chemokines and their respective receptors during the experimental P. berghei infection. Increased expression of ECM components was observed in thymi from infected mice. In contrast, down‐regulated surface expression of fibronectin and laminin receptors was observed in thymocytes from these animals. Moreover, in thymi from infected mice there was increased CXCL12 and CXCR4, and a decreased expression of CCL25 and CCR9. An altered thymocyte migration towards ECM elements and chemokines was seen when the thymi from infected mice were analysed. Evaluation of ex vivo migration patterns of CD4/CD8‐defined thymocyte subpopulations revealed that double‐negative (DN), and CD4+ and CD8+ single‐positive (SP) cells from P. berghei‐infected mice have higher migratory responses compared with controls. Interestingly, increased numbers of DN and SP subpopulations were found in the spleens of infected mice. Overall, we show that the thymic atrophy observed in P. berghei‐infected mice is accompanied by thymic microenvironmental changes that comprise altered expression of thymocyte migration‐related molecules of the ECM and chemokine protein families, which in turn can alter the thymocyte migration pattern. These thymic disturbances may have consequences for the control of the immune response against this protozoan.
The self‐antigen, thyroglobulin, induces antigen‐experienced CD4+ T cells from healthy donors to proliferate and promote production of the regulatory cytokine, interleukin‐10, by monocytes
Authors: Nielsen Claus H. , Galdiers Marcel P. , Hedegaard Chris J. , Leslie R. Graham Q.
Published: September 2009

Thyroglobulin (TG), as autoantigen, induces in vitro proliferation of T and B cells from normal individuals, but the cytokine production differs from that in patients with autoimmune thyroid disease. Here, we investigate whether normal T cells responding to TG are naive, or have previously encountered TG in vivo, using their responses to classic primary and secondary antigens, keyhole limpet haemocyanin (KLH) and tetanus toxoid (TT), respectively, for comparison. While TG elicited T‐cell proliferation kinetics typical of a secondary response, the cytokine profile was distinct from that for TT. Whereas TT induced pro‐inflammatory cytokines [interleukin‐2 (IL‐2)/interferon‐γ (IFN‐γ)/IL‐4/IL‐5], TG evoked persistent release of the regulatory IL‐10. Some donors, however, also responded with late IFN‐γ production, suggesting that the regulation by IL‐10 could be overridden. Although monocytes were prime producers of IL‐10 in the early TG response, a few IL‐10‐secreting CD4+ T cells, primarily with CD45RO+ memory phenotype, were also detected. Furthermore, T‐cell depletion from the mononuclear cell preparation abrogated monocyte IL‐10 production. Our findings indicate active peripheral tolerance towards TG in the normal population, with aberrant balance between pro‐ and anti‐inflammatory cytokine responses for some donors. This observation has implications for autoantigen recognition in general, and provides a basis for investigating the dichotomy between physiological and pathological modes of auto‐recognition.
Biodiversity changes in a shallow lake ecosystem: a multi‐proxy palaeolimnological analysis
Authors: Sayer C. , Roberts N. , Sadler J. , David C. , Wade P. M.
Published: September 2009

Biodiversity is a key measure of environmental quality in lake ecosystems. Lake biodiversity can be assessed using modern survey data, but typically these data only provide a ‘snap‐shot’ measure and in most cases it is not possible to reconstruct temporal trends in biodiversity, so that human impacts can be detected. Palaeoecological techniques offer an alternative means of identifying changes in biodiversity over the period of historical records and far beyond, but there are problems associated with this approach. This is because only a select set of organisms leave a trace in the sediment record such that it is not usually possible to make reliable assessments of diversity changes within an entire taxonomic order (e.g. the algae). Moreover these organisms are typically from the lower levels of the trophic hierarchy (i.e. plants and insects).

The problems of identifying changes in biodiversity from the palaeolimnological record are addressed with reference to Groby Pool, a shallow, eutrophic, medieval lake in the English Midlands, which has been subjected to eutrophication over the last 150 years. 210Pb and 137Cs‐dated sediment cores have been used to estimate short‐term alterations in the composition and diversity of three groups of indicators, representing different levels in the trophic cascade, namely diatoms, aquatic pollen and chironomids. By exploring relationships, both between these indicators and with archival macrophyte records, an assessment is made of eutrophication‐related changes in overall habitat diversity at the ecosystem level. These data suggest that the lake has undergone considerable nutrient enrichment, resulting in the loss of a diverse, mesotrophic macrophyte flora from at least the turn of the century onwards and its replacement by a few highly competitive species tolerant of high nutrient concentrations. Reductions in macrophyte diversity seem to be reflected palaeoecologically by a decline in the diversity of fossil chironomid assemblages, related to the breakdown of particular host‐plant relationships amongst the phytophagic species. However, diatom assemblages generally exhibit the opposite trend, which may be related to increases in macrophyte cover and increasing opportunities for the colonization of diverse epiphyte communities. The different fossil indicators have different limitations and merits, and for this reason a ‘multi‐proxy’ approach is essential if meaningful inferences are to be made of changes in lake biodiversity using palaeoecological data.