bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ribonucleotide Reductase Regulation in Response to Genotoxic Stress in Arabidopsis
Authors: Roa Hélène , Lang Julien , Culligan Kevin M. , Keller Murielle , Holec Sarah , Cognat Valérie , Montané Marie-Hélène , Houlné Guy , Chabouté Marie-Edith 
Published: July 2009

Abstract
Ribonucleotide reductase (RNR) is an essential enzyme that provides dNTPs for DNA replication and repair. Arabidopsis (Arabidopsis thaliana) encodes three AtRNR2-like catalytic subunit genes (AtTSO2, AtRNR2A, and AtRNR2B). However, it is currently unclear what role, if any, each gene contributes to the DNA damage response, and in particular how each gene is transcriptionally regulated in response to replication blocks and DNA damage. To address this, we investigated transcriptional changes of 17-d-old Arabidopsis plants (which are enriched in S-phase cells over younger seedlings) in response to the replication-blocking agent hydroxyurea (HU) and to the DNA double-strand break inducer bleomycin (BLM). Here we show that AtRNR2A and AtRNR2B are specifically induced by HU but not by BLM. Early AtRNR2A induction is decreased in an atr mutant, and this induction is likely required for the replicative stress checkpoint since rnr2a mutants are hypersensitive to HU, whereas AtRNR2B induction is abolished in the rad9-rad17 double mutant. In contrast, AtTSO2 transcription is only activated in response to double-strand breaks (BLM), and this activation is dependent upon AtE2Fa. Both TSO2 and E2Fa are likely required for the DNA damage response since tso2 and e2fa mutants are hypersensitive to BLM. Interestingly, TSO2 gene expression is increased in atr versus wild type, possibly due to higher ATM expression in atr. On the other hand, a transient ATR-dependent H4 up-regulation was observed in wild type in response to HU and BLM, perhaps linked to a transient S-phase arrest. Our results therefore suggest that individual RNR2-likecatalytic subunit genes participate in unique aspects of the cellular response to DNA damage in Arabidopsis.
Multiple Sequence Motifs in the Rubisco Small Subunit Transit Peptide Independently Contribute to Toc159-Dependent Import of Proteins into Chloroplasts
Authors: Lee Dong Wook , Lee Sumin , Oh Young Jun , Hwang Inhwan 
Published: July 2009

AbstractA large number of plastid proteins encoded by the nuclear genome are posttranslationally imported into plastids by at least two distinct mechanisms: the Toc159-dependent and Toc132/Toc120-dependent pathways. Light-induced photosynthetic proteins are imported through the Toc159-dependent pathway, whereas constitutive housekeeping plastid proteins are imported into plastids through the Toc132/Toc120 pathway. However, it remains unknown which features of the plastid protein transit peptide (TP) determine the import pathway. We have discovered sequence elements of the Rubisco small subunit TP (RbcS-tp) that play a role in determining import through the Toc159-dependent pathway in vivo. We generated multiple hybrid mutants using the RbcS-tp and the E1α-subunit of pyruvate dehydrogenase TP (E1α-tp) as representative peptides mediating import through the Toc159-dependent and Toc159-independent pathways, respectively. Import experiments using these hybrid mutants in wild-type and ppi2 mutant protoplasts revealed that multiple sequence motifs in the RbcS-tp independently contribute to Toc159-dependent protein import into chloroplasts. One of these motifs is the group of serine residues located in the N-terminal 12-amino acid segment and the other is the C-terminal T5 region of the RbcS-tp ranging from amino acid positions 41 to 49. Based on these findings, we propose that multiple sequence elements in the RbcS-tp contribute independently to Toc159-dependent import of proteins into chloroplasts.
Integrated Metabolite and Transcript Profiling Identify a Biosynthetic Mechanism for Hispidol in Medicago truncatula Cell Cultures
Authors: Farag Mohamed A. , Deavours Bettina E. , de Fátima Ângelo , Naoumkina Marina , Dixon Richard A. , Sumner Lloyd W. 
Published: July 2009

Abstract
Metabolic profiling of elicited barrel medic (Medicago truncatula) cell cultures using high-performance liquid chromatography coupled to photodiode and mass spectrometry detection revealed the accumulation of the aurone hispidol (6-hydroxy-2-[(4-hydroxyphenyl)methylidene]-1-benzofuran-3-one) as a major response to yeast elicitor. Parallel, large-scale transcriptome profiling indicated that three peroxidases, MtPRX1, MtPRX2, and MtPRX3, were coordinately induced with the accumulation of hispidol. MtPRX1 and MtPRX2 exhibited aurone synthase activity based upon in vitro substrate specificity and product profiles of recombinant proteins expressed in Escherichia coli. Hispidol possessed significant antifungal activity relative to other M. truncatula phenylpropanoids tested but has not been reported in this species before and was not found in differentiated roots in which high levels of the peroxidase transcripts accumulated. We propose that hispidol is formed in cell cultures by metabolic spillover when the pool of its precursor, isoliquiritigenin, builds up as a result of an imbalance between the upstream and downstream segments of the phenylpropanoid pathway, reflecting the plasticity of plant secondary metabolism. The results illustrate that integration of metabolomics and transcriptomics in genetically reprogrammed plant cell cultures is a powerful approach for the discovery of novel bioactive secondary metabolites and the mechanisms underlying their generation.
DICKKOPF‐4 and ‐2 genes are upregulated in human colorectal cancer
Authors: Matsui Akira , Yamaguchi Tatsuya , Maekawa Shinya , Miyazaki Chikako , Takano Shinichi , Uetake Tomoyoshi , Inoue Taisuke , Otaka Masahiko , Otsuka Hiroyuki , Sato Tadashi , Yamashita Atsuya , Takahashi Yuka , Enomoto Nobuyuki 
Published: July 2009

To comprehensively screen for genetic events underlying colorectal cancer, we performed suppression subtraction hybridization analysis on an advanced colon cancer. Because Dickkopf‐4, a member of the Dickkopf family acting as a Wnt‐signaling modulator, was identified as one of the upregulated genes in this specimen, we investigated expression profiles of all the Dickkopf family members in 55 colorectal tumors (21 cancers and 34 adenomas). We also investigated mechanisms regulating the expression of Dickkopf‐4 in these cancers in vitro and in vivo. Compared with normal adjacent mucosae, Dickkopf‐4 (median 27.4, P < 0.01) and ‐2 (median 51.4, P < 0.01) were strongly expressed in colorectal cancers. The level of Dickkopf‐4 was positively correlated with fibroblast growth factor‐20 (rs = 0.61, P = 0.00017), a representative β‐catenin transcriptional target gene, and with the degree of nuclear accumulation of β‐catenin in colorectal tumors. Dickkopf‐4 was induced by activated β‐catenin in vitro. Reciprocally, recombinant Dickkopf‐4 significantly inhibited T‐cell factor/lymphocyte enhancer factor reporter activity stimulated by recombinant Wnt3a in human embryonic kidney 293 cells. We conclude that Dickkopf‐4 and ‐2 are significantly upregulated in most colorectal tumors, and that Dickkopf‐4 upregulation reflects activation of the Wnt/canonical pathway. (Cancer Sci 2009; 100: 1923–1930)
Usefulness of cumulative smoking dose for identifying the EGFR mutation and patients with non‐small‐cell lung cancer for gefitinib treatment
Authors: Jida Masaru , Toyooka Shinichi , Mitsudomi Tetsuya , Takano Toshimi , Matsuo Keitaro , Hotta Katsuyuki , Tsukuda Kazunori , Kubo Takafumi , Yamamoto Hiromasa , Yamane Masaomi , Oto Takahiro , Sano Yoshifumi , Kiura Katsuyuki , Yatabe Yasushi , Ohe Yuichiro , Date Hiroshi , Miyoshi Shinichiro 
Published: July 2009

We examined the diagnostic accuracy of the cumulative smoking dose for identifying the epidermal growth factor receptor (EGFR) exon 19 deletion and L858R mutation among Japanese patients with non‐small‐cell lung cancer (NSCLC). EGFR mutations in exon 19 and exon 21 were determined in 1001 NSCLC patients. A receiver–operating characteristic (ROC) curve methodology was applied to estimate the diagnostic accuracy. EGFR mutations were detected in 314 patients (31.4%). A cumulative smoking dose of less than 13 pack‐years (PY) was the optimal cut‐off point for predicting a positive EGFR mutation status, producing a balance between the sensitivity (73.5%) and the specificity (77%). The area under the ROC curve was 0.77, indicating that the smoking dose had a moderate diagnostic accuracy. The median survival time or the median progression‐free survival time of patients who had smoked less than 13 pack‐years (PY) were 18.6 and 6.3 months, respectively, while those of patients with equal to or more than 13 PY were 9.6 and 2.4 months, respectively. The overall survival (OS) and progression‐free survival (PFS) rates were significantly different between the two groups (OS: hazard ratio [HR] = 0.64, 95% confidence interval [CI] = 0.51–0.80, P = 0.0001) (PFS: HR = 0.58, 95% CI = 0.47–0.71, P < 0.0001). Our study indicated that the smoking dose predicted EGFR mutations with a moderate diagnostic accuracy. Thus, patients who have smoked less than 13 PY might be candidates for gefitinib treatment when EGFR mutation status cannot be determined. (Cancer Sci 2009; 100: 1931–1934)
Review article: gastric electrical stimulation for gastroparesis – physiological foundations, technical aspects and clinical implications
Authors: SOFFER E. , ABELL T. , LIN Z. , LORINCZ A. , MCCALLUM R. , PARKMAN H. , POLICKER S. , ORDOG T. 
Published: July 2009

SummaryBackground  Application of electrical stimulation to the gut, primarily the stomach, has rapidly advanced in the last two decades, from mostly animal studies to the clinical arena. Most studies focused on the use of electrical stimulation for gastroparesis, the only approved indication for such intervention.Aim  To review the physiological basis of gastric electrical activity and the technical aspects and clinical outcome of gastric electrical stimulation (GES) for gastroparesis.Methods  PubMed search from 1966 to 2009, using gastroparesis and GES as search terms. Areas in focus were systematically reviewed.Results  The literature consists of open‐label studies, mostly from single centres, published in the last decade. Improvement in symptoms, quality of life and nutritional status was reported by most studies. Physiologically, stimulation parameters approved in clinical practice do not regulate gastric slow wave activity and have inconsistent effect on gastric emptying. The mechanism of action of GES is not fully known, but data support modulation of gastric biomechanical activity and afferent neural mechanisms.Conclusions  Gastric electrical stimulation is a helpful intervention in recalcitrant gastroparesis. Controlled studies and better understanding of mechanisms of action of electrical stimulation are needed to evaluate further the clinical utility of this intervention and to exploit its therapeutic potential better.
Therapeutic intent of proton pump inhibitor prescription among elderly nonsteroidal anti‐inflammatory drug users
Authors: DRIES A. M. , RICHARDSON P. , CAVAZOS J. , ABRAHAM N. S. 
Published: July 2009

SummaryBackground  Prescription of proton pump inhibitors (PPIs) has increased dramatically.Aim  To assess therapeutic intent of PPI prescription among elderly veterans prescribed nonsteroidal anti‐inflammatory drugs.Methods  Medical‐record abstraction identified therapeutic intent of PPI prescription. An ‘appropriate therapeutic intent’ was defined as symptomatic gastro‐oesophageal reflux disease or endoscopic oesophagitis, Zollinger–Ellison disease, dyspepsia, upper gastrointestinal event, Helicobacter pylori infection or nonsteroidal anti‐inflammatory drug gastroprotection. Logistic regression predicted the outcome while adjusting for clinical characteristics.Results  Of 1491 patients [mean 73 years (s.d. 5.6), 73% white and 99.8% men], among those charts which did document a therapeutic indication, 88.8% were appropriate. Prior gastroscopy was predictive of an appropriate therapeutic intent (OR 2.7; 95% CI: 1.9–3.7). Prescription to patients who used VA pharmacy services only, to in‐patients, or by a cardiologist or an otolaryngologist were less likely to be appropriate. Gastroprotection was poorly recognized as an indication for PPI prescription, except by rheumatologists (OR 46.7; 95% CI: 15.9–136.9), or among highly co‐morbid patients (OR 1.8; 95% CI: 1.1–2.9). Among in‐patients, 45% of PPI prescriptions were initiated for unknown or inappropriate reasons.Conclusions  Type of provider predicts appropriate PPI use. In‐patient prescription is associated with poor recognition of necessary gastroprotection and unknown therapeutic intent.
Carbon source for reproduction in a spring ephemeral herb, Corydalis ambigua (Papaveraceae)
Authors: Kudo Gaku , Ida Takashi Y. 
Published: July 2009

Summary 1. The carbon source for reproduction in plants may differ between flowering and fruiting stages. To clarify how spring ephemerals use current photosynthetic products for reproduction, the allocation patterns of photosynthate at flowering and fruiting and the effects of resource limitation on reproductive performance in Corydalis ambigua were assessed. 2. A 13C tracing experiment revealed that about 20% of the current photosynthetic carbon was used for reproduction at both flowering and fruiting. The proportion of 13C allocated to fruits was constant irrespective of the light level. In contrast, 13C translocation to tubers increased at fruiting, and this trend was accelerated when plants were shaded. 3. Defoliation treatment significantly reduced nectar production and tuber mass, while seed production was not affected. Therefore, when carbon assimilation was limited, carbon was preferentially allocated to current reproduction (seeds) rather than to pollinator attraction (nectar) or storage (tuber). 4. If seed production is partly supported by carbohydrate reserved in the old tissue of tubers, nectar and seed production may not compete strongly for carbon sources. In contrast to the ability of high seed production, the susceptibility of nectar production to current photosynthesis indicates that seed production of this species is basically limited by pollen capture. 5. Therefore, temporal separation of resource pool for reproduction may mitigate the joint limitation of seed production between pollinator attraction and resource availability. Temporal variation of the sink–source balance of storage organ is crucial to understand the cost of reproduction in perennial plants.
Mechanism and cost of synchronous hatching
Authors: Colbert Paul L. , Spencer Ricky‐John , Janzen Fredric J. 
Published: July 2009

Summary1.Synchrony in the timing of births is thought to have evolved as a general predator avoidance strategy. In turtles, synchronous hatching may facilitate group emergence from the nest, which in turn, may limit predation by diluting an individual’s risk of predation or by simply swamping predators upon emergence. However, synchronizing hatching should not be easily achieved in natural nests because of thermal gradients affecting developmental rates.2.We evaluated pipping synchrony in the painted turtle (Chrysemys picta), where the drive to hatch synchronously may be reduced, because in many populations, hatching and emergence are dissociated through hatchlings overwintering within a nest.3.We also assessed developmental mechanisms through which synchrony occurs and explored potential trade‐offs between pipping synchrony and individual fitness by determining potential short and long‐term neuromuscular developmental costs to hatching prematurely. These data were also used to develop a theoretical model to determine how differential embryonic maturation rates affect hatching synchrony.4.Underdeveloped embryos pipped much earlier than expected and at similar times to their more advanced sibs. In addition, a trade‐off between hatching synchronously and neuromuscular development (motility) was evident several days after hatching and up to 9 months later, after the overwintering period.5.Synchronous hatching is an ancestral trait in turtles, but its relevance today is not solely for predator avoidance in all species.6.Abiotic factors during incubation (e.g. temperature regime and moisture) have long‐term effects on reptiles during ontogeny but it is also clear that incubation behaviour is major factor for the persistence of these developmental costs.
Global bottlenecks in the distribution of marine Crustacea: temperature constraints in the family Lithodidae
Authors: Hall Sally , Thatje Sven 
Published: July 2009

AbstractAim  Members of the crustacean family Lithodidae share preferences for cold‐water environments; however, the specific role of temperature in governing lithodid biogeography has not been examined to date. In the present study this relationship was quantified through the analysis of habitat data, and the results were interpreted in the light of previous physiological studies. It was hypothesized that lineage‐specific temperature thresholds underlie differences in the distribution of the two lithodid subfamilies.Location  The family Lithodidae is divided into the subfamilies Hapalogastrinae and Lithodinae. The Hapalogastrinae inhabit depths of between 0 and 200 m in the North Pacific. The Lithodinae are distributed globally in the deep sea, with a few genera occurring intertidally at high latitudes.Methods  Descriptions of 86 species of lithodids, sampled at 627 locations worldwide, were obtained from a wide range of published and original sources. For each specimen, the water temperature at the time and locality of collection was recorded. Molecular sequence data for the 16S, cytochrome c oxidase subunit I (COI) and 28S genes were analysed to construct a phylogenetic tree for the major lithodid genera, using a maximum likelihood method in the program paup*. Further analyses examined the link between the habitat temperature range and the position of taxa within the lithodid phylogeny.Results  Phylogenetic evidence indicated that the deep‐water lithodid lineages had ancestors that inhabited the coastal waters of the North Pacific. Adults of North Pacific lithodid taxa were found in regions where water temperatures ranged from 0 to 25°C; however, deep‐water lineages of the Lithodinae were excluded from waters exceeding temperatures of 13°C. Despite the higher temperatures tolerated by adults, North Pacific intertidal/subtidal genera were restricted to regions that had water temperatures lower than 16°C during periods of larval development.Main conclusions  Temperature has restricted the range of most shallow‐water genera of Lithodidae to the coastline of the North Pacific since the early history of the family. Distribution in these groups remains constrained by the detrimental effects of temperature extremes on early life‐history stages. Deep‐water lineages moved away from seasonal temperature fluctuations, and underwent at least three radiations into water bodies outside the North Pacific. Species from within the deep‐water lineages currently live close to the threshold of their temperature tolerance in the Southern Ocean, and their future distribution may be affected by increases in ocean temperature.
Foxp3 expression in lesions of the different clinical forms of American tegumentary leishmaniasis
Authors: CARNEIRO F. P. , DE MAGALHÃES A. V. , DE JESUS ABREU ALMEIDA COUTO M. , BOCCA A. L. , MUNIZ‐JUNQUEIRA M. I. , RIBEIRO SAMPAIO R. N. 
Published: July 2009

SummaryAs the diversity in clinical presentation of American tegumentary leishmaniasis (ATL) is determined mainly by the immune response of host, our aim was to evaluate the in situ expression of Foxp3 [marker of regulatory T (Treg) cell] in lesions of the different clinical forms of ATL. Foxp3+ cells were observed in 39·5% (32/81) of the samples and the number of positive cells was low in all the clinical forms. Even presenting a significantly lower number of CD4+ T cells, diffuse cutaneous leishmaniasis (DCL) showed a higher expression of Foxp3 when compared with localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). In LCL and MCL, the number of Foxp3+ cells correlated positively with the number of apoptotic cells (active caspase‐3+ cells). A positive correlation was also observed between the expression of active caspase‐3 and FasL in these clinical forms. Our data suggest that increased number of Treg cells may be associated to the hyporesponsiveness observed in DCL and also indicate that the apoptosis may be a possible mechanism of action of Foxp3+ Treg cell in LCL and MCL. However, further studies are required to better understand the mechanism of action of Treg cell.
Immunospecific immunoglobulins and IL‐10 as markers for Trypanosoma brucei rhodesiense late stage disease in experimentally infected vervet monkeys
Authors: Ngotho M. , Kagira J. M. , Jensen H. E. , Karanja S. M. , Farah I. O. , Hau J. 
Published: July 2009

SummaryObjective  To determine the usefulness of IL‐10 and immunoglobulin M (IgM) as biomarkers for staging HAT in vervet monkeys, a useful pathogenesis model for humans.Methods  Vervet monkeys were infected with Trypanosoma brucei rhodesiense and subsequently given sub‐curative and curative treatment 28 and 140 days post‐infection (dpi) respectively. Matched serum and CSF samples were obtained at regular intervals and immunospecific IgM, immunoglobulin G (IgG) and IL‐10 were quantified by ELISA.Results  There was no detectable immunospecific IgM and IgG in the CSF before 49 dpi. CSF IgM and IgG and serum IgM were significantly elevated with peak levels coinciding with meningoencephalitis 98 dpi. The serum IL‐10 was upregulated in both early and late disease stage, coinciding with primary and relapse parasitaemia respectively. CSF white cell counts (CSF WCC) were elevated progressively till curative treatment was given. After curative treatment, there was rapid and significant drop in serum IgM and IL‐10 concentration as well as CSF WCC. However, the CSF IgM and IgG remained detectable to the end of the study.Conclusions  Serum and CSF concentrations of immunospecific IgM and CSF IgG changes followed a pattern that mimics the progression of the disease and may present reliable and useful biomarkers of the disease stage. Due to rapid decline, serum IgM and IL‐10 are, additionally, potential biomarkers of the success of chemotherapy.
The angiosperm radiation revisited, an ecological explanation for Darwin’s ‘abominable mystery’
Authors: Berendse Frank , Scheffer Marten 
Published: July 2009

AbstractOne of the greatest terrestrial radiations is the diversification of the flowering plants (Angiospermae) in the Cretaceous period. Early angiosperms appear to have been limited to disturbed, aquatic or extremely dry sites, suggesting that they were suppressed in most other places by the gymnosperms that still dominated the plant world. However, fossil evidence suggests that by the end of the Cretaceous the angiosperms had spectacularly taken over the dominant position from the gymnosperms around the globe. Here, we suggest an ecological explanation for their escape from their subordinate position relative to gymnosperms and ferns. We propose that angiosperms due to their higher growth rates profit more rapidly from increased nutrient supply than gymnosperms, whereas at the same time angiosperms promote soil nutrient release by producing litter that is more easily decomposed. This positive feedback may have resulted in a runaway process once angiosperms had reached a certain abundance. Evidence for the possibility of such a critical transition to angiosperm dominance comes from recent work on large scale vegetation shifts, linking long‐term field observations, large scale experiments and the use of simulation models.