bluuebunny/crossref_metadata_2025 huggingface dataset:
Aryl Hydrocarbon Receptor-Interacting Protein Gene Mutations in Familial Isolated Pituitary Adenomas: Analysis in 73 Families
Authors: Daly Adrian F. , Vanbellinghen Jean-François , Khoo Sok Kean , Jaffrain-Rea Marie-Lise , Naves Luciana A. , Guitelman Mirtha A. , Murat Arnaud , Emy Philippe , Gimenez-Roqueplo Anne-Paule , Tamburrano Guido , Raverot Gérald , Barlier Anne , De Herder Wouter , Penfornis Alfred , Ciccarelli Enrica , Estour Bruno , Lecomte Pierre , Gatta Blandine , Chabre Olivier , Sabaté María Isabel , Bertagna Xavier , Garcia Basavilbaso Natalia , Stalldecker Graciela , Colao Annamaria , Ferolla Piero , Wémeau Jean-Louis , Caron Philippe , Sadoul Jean-Louis , Oneto Adriana , Archambeaud Françoise , Calender Alain , Sinilnikova Olga , Montañana Carmen Fajardo , Cavagnini Francesco , Hana Vaclav , Solano Angela , Delettieres Dreanina , Luccio-Camelo Douglas C. , Basso Armando , Rohmer Vincent , Brue Thierry , Bours Vincent , Teh Bin Tean , Beckers Albert
Published: January 2007

Context: An association between germline aryl hydrocarbon receptor-interacting protein (AIP) gene mutations and pituitary adenomas was recently shown.

Objective: The objective of the study was to assess the frequency of AIP gene mutations in a large cohort of patients with familial isolated pituitary adenoma (FIPA).

Design: This was a multicenter, international, collaborative study.

Setting: The study was conducted in 34 university endocrinology and genetics departments in nine countries.

Patients: Affected members from each FIPA family were studied. Relatives of patients with AIP mutations underwent AIP sequence analysis.

Main Outcome Measures: Presence/absence and description of AIP gene mutations were the main outcome measures.

Intervention: There was no intervention.

Results: Seventy-three FIPA families were identified, with 156 patients with pituitary adenomas; the FIPA cohort was evenly divided between families with homogeneous and heterogeneous tumor expression. Eleven FIPA families had 10 germline AIP mutations. Nine mutations, R16H, G47_R54del, Q142X, E174frameshift, Q217X, Q239X, K241E, R271W, and Q285frameshift, have not been described previously. Tumors were significantly larger (P = 0.0005) and diagnosed at a younger age (P = 0.0006) in AIP mutation-positive vs. mutation-negative subjects. Somatotropinomas predominated among FIPA families with AIP mutations, but mixed GH/prolactin-secreting tumors, prolactinomas, and nonsecreting adenomas were also noted. Approximately 85% of the FIPA cohort and 50% of those with familial somatotropinomas were negative for AIP mutations.

Conclusions: AIP mutations, of which nine new mutations have been described here, occur in approximately 15% of FIPA families. Although pituitary tumors occurring in association with AIP mutations are predominantly somatotropinomas, other tumor types are also seen. Further study of the impact of AIP mutations on protein expression and activity is necessary to elucidate their role in pituitary tumorigenesis in FIPA.
Negative regulation of Activin/Nodal signaling by SRF duringXenopusgastrulation
Authors: Yun Chang-Hyun , Choi Sun-Cheol , Park Eunjoo , Kim Seong-Jin , Chung An-Sik , Lee Hyeong-Kyu , Lee Ho-Jae , Han Jin-Kwan
Published: January 2007

Activin/Nodal signaling is essential for germ-layer formation and axial patterning during embryogenesis. Recent evidence has demonstrated that the intra- or extracellular inhibition of this signaling is crucial for ectoderm specification and correct positioning of mesoderm and endoderm. Here, we analyzed the function of Xenopus serum response factor (XSRF) in establishing germ layers during early development. XSRF transcripts are restricted to the animal pole ectoderm in Xenopus early embryos. Ectopic expression of XSRF RNA suppresses mesoderm induction, both in the marginal zone in vivo and caused by Activin/Nodal signals in animal caps. Dominant-negative mutant or antisense morpholino oligonucleotide-mediated inhibition of XSRF function expands the expression of mesendodermal genes toward the ectodermal territory and enhances the inducing activity of the Activin signal. SRF interacts with Smad2 and FAST-1, and inhibits the formation of the Smad2-FAST-1 complex induced by Activin. These results suggest that XSRF might act to ensure proper mesoderm induction in the appropriate region by inhibiting the mesoderm-inducing signals during early embryogenesis.
Hypothesis: RNA editing of microRNA target sites in humans?
Authors: Liang Han , Landweber Laura F.
Published: January 2007

Adenosine (A) to inosine (I) RNA editing occurs widely in the human transcriptome, and a large proportion of editing sites are within untranslated regions (UTRs). MicroRNAs (miRNAs), an abundant class of regulatory genes, specify the expression of a large number of target genes by pairing to their 3′ UTRs. To study the interplay between these two post-transcriptional events, we developed a computational pipeline to integrate sequence and miRNA tissue specificity data. The results show that some A-to-I RNA editing positions have a potential to block the miRNA:target recognition, although further computational simulation suggests that RNA editing tends to avoid miRNA target sites in general. We propose that a small proportion of RNA editing events may provide an additional layer of control on miRNA-mediated repression. Further investigation is needed to elucidate the functional effect of these special RNA editing events.
Osteogenic protein-1 increases the fixation of implants grafted with morcellised bone allograft and ProOsteon bone substitute
Authors: Jensen T. B. , Overgaard S. , Lind M. , Rahbek O. , Bünger C. , Søballe K.
Published: January 2007

Impacted bone allograft is often used in revision joint replacement. Hydroxyapatite granules have been suggested as a substitute or to enhance morcellised bone allograft. We hypothesised that adding osteogenic protein-1 to a composite of bone allograft and non-resorbable hydroxyapatite granules (ProOsteon) would improve the incorporation of bone and implant fixation. We also compared the response to using ProOsteon alone against bone allograft used in isolation. We implanted two non-weight-bearing hydroxyapatite-coated implants into each proximal humerus of six dogs, with each implant surrounded by a concentric 3 mm gap. These gaps were randomly allocated to four different procedures in each dog: 1) bone allograft used on its own; 2) ProOsteon used on its own; 3) allograft and ProOsteon used together; or 4) allograft and ProOsteon with the addition of osteogenic protein-1.

After three weeks osteogenic protein-1 increased bone formation and the energy absorption of implants grafted with allograft and ProOsteon. A composite of allograft, ProOsteon and osteogenic protein-1 was comparable, but not superior to, allograft used on its own.

ProOsteon alone cannot be recommended as a substitute for allograft around non-cemented implants, but should be used to extend the volume of the graft, preferably with the addition of a growth factor.
Interleukin-6, procalcitonin and TNF-α
Authors: Bottner F. , Wegner A. , Winkelmann W. , Becker K. , Erren M. , Götze C.
Published: January 2007

This prospective study evaluates the role of new laboratory markers in the diagnosis of deep implant infection in 78 patients (41 men and 37 women) with a revision total knee or hip replacement.

The mean age at the time of operation was 64.0 years (19 to 90). Intra-operative cultures showed that 21 patients had a septic and 57 an aseptic total joint replacement. The white blood cell count, the erythrocyte sedimentation rate and levels of C-reactive protein, interleukin-6, procalcitonin and tumour necrosis factor (TNF)-α were measured in blood samples before operation. The diagnostic cut-off values were determined by Received Operating Characteristic curve analysis.

C-reactive protein (> 3.2 md/dl) and interleukin-6 (> 12 pg/ml) have the highest sensitivity (0.95). Interleukin-6 is less specific than C-reactive protein (0.87 vs 0.96). Combining C-reactive protein and interleukin-6 identifies all patients with deep infection of the implant. Procalcitonin (> 0.3 ng/ml) and TNF-α (> 40 ng/ml) are very specific (0.98 vs 0.94) but have a low sensitivity (0.33 vs 0.43).

The combination of C-reactive protein and interleukin-6 measurement provide excellent screening tests for infection of a deep implant. A highly specific marker such as procalcitonin and pre-operative aspiration of the joint might be useful in identifying patients with true positive C-reactive protein and/or interleukin-6 levels.
Determining the rotational alignment of the tibial component at total knee replacement
Authors: Ikeuchi M. , Yamanaka N. , Okanoue Y. , Ueta E. , Tani T.
Published: January 2007

We prospectively assessed the benefits of using either a range-of-movement technique or an anatomical landmark method to determine the rotational alignment of the tibial component during total knee replacement. We analysed the cut proximal tibia intraoperatively, determining anteroposterior axes by the range-of-movement technique and comparing them with the anatomical anteroposterior axis.

We found that the range-of-movement technique tended to leave the tibial component more internally rotated than when anatomical landmarks were used. In addition, it gave widely variable results (mean 7.5°; 2° to 17°), determined to some extent by which posterior reference point was used. Because of the wide variability and the possibilities for error, we consider that it is inappropriate to use the range-of-movement technique as the sole method of determining alignment of the tibial component during total knee replacement.
Hydroxyapatite-coated total knee replacement
Authors: Epinette J.-A. , Manley M. T.
Published: January 2007

This study describes 146 primary total knee replacements, either fully or partially coated with hydroxyapatite of which 74 knees in 68 patients were available for clinical and radiological assessment at a mean of 11.2 years (10 to 15). The global failure rate was 1.37% and survival rate with mechanical failure as the end-point was 98.14%. Radiological assessment indicated intimate contact between bone and the hydroxyapatite coating. Over time the hydroxyapatite coating appears to encourage filling of interface gaps remaining after surgery. Our results compare favourably with those of series describing cemented or porous-coated knee replacements, and suggest that fixation with hydroxyapatite is a reliable option in primary total knee replacement.
Tibiofibular synostosis in a professional football player
Authors: James S. H. , Carpenter E. C. , Fairclough J. A.
Published: January 2007

We present an unusual cause of anterior tibial pain in a 24-year-old professional international football player who was found to have a synostosis of the middle-third of the diaphysis of the tibia and fibula.

This is a rarely described phenomenon. Conservative treatment is the recommended treatment of choice, but this failed in our patient. Resection produced resolution of symptoms; he remained symptom-free three years later.
The femoral head/neck offset and hip resurfacing
Authors: Beaulé P. E. , Harvey N. , Zaragoza E. , Le Duff M. J. , Dorey F. J.
Published: January 2007

Because the femoral head/neck junction is preserved in hip resurfacing, patients may be at greater risk of impingement, leading to abnormal wear patterns and pain. We assessed femoral head/neck offset in 63 hips undergoing metal-on-metal hip resurfacing and in 56 hips presenting with non-arthritic pain secondary to femoroacetabular impingement. Most hips undergoing resurfacing (57%; 36) had an offset ratio ≤ 0.15 pre-operatively and required greater correction of offset at operation than the rest of the group. In the non-arthritic hips the mean offset ratio was 0.137 (0.04 to 0.23), with the offset ratio correlating negatively to an increasing α angle. An offset ratio ≤ 0.15 had a 9.5-fold increased relative risk of having an α angle ≥ 50.5°. Most hips undergoing resurfacing have an abnormal femoral head/neck offset, which is best assessed in the sagittal plane.
Revision total hip replacement using the Kerboull acetabular reinforcement device with morsellised or bulk graft
Authors: Kawanabe K. , Akiyama H. , Onishi E. , Nakamura T.
Published: January 2007

We retrospectively evaluated 42 hips which had undergone acetabular reconstruction using the Kerboull acetabular reinforcement device between September 1994 and December 1998. We used autogenous bone chips from the ilium and ceramic particle morsellised grafts, even in large acetabular bone defects, in the early stages of the study. Thereafter, femoral head allograft was used as bulk graft in patients with large acetabular defects. Ceramic blocks and the patients’ contralateral femoral head were also used as bulk graft. The mean follow-up period was 8.7 years (4.3 to 12).

Survivorship analysis was performed using radiological failure of the acetabular component, irrespective of whether it was revised, or not, as the end-point.

The survival rate of the morsellised graft group (25 hips) and the bulk graft group (17 hips) at ten years was 53% (95% confidence interval (CI) 42.5% to 63.5%) and 82% (95% CI 72.4% to 91.6%), respectively. The mid-term results of revision total hip replacement with the Kerboull device were better when bulk graft was used in any size of bone defect.
Urinary catheter tamponade to control intra-operative bleeding from the superior gluteal artery
Authors: Konangamparambath S. , Wilkinson J. M. , Cleveland T. , Stockley I.
Published: January 2007

Bleeding is a major complication of revision total hip replacement. We report a case where the inflated balloon of a urinary catheter was used to temporarily control intrapelvic bleeding from the superior gluteal artery, while definitive measures for endovascular embolisation were made.
The outcome of peri-operative humeral condylar fractures after total elbow replacement in patients with rheumatoid arthritis
Authors: Ito H. , Matsumoto T. , Yoshitomi H. , Kakinoki R. , Nakamura T.
Published: January 2007

We compared the outcome of peri-operative humeral condylar fractures in patients undergoing a Coonrad-Morrey semiconstrained total elbow replacement with that of patients with rheumatoid arthritis undergoing the same procedure without fractures. In a consecutive series of 40 elbows in 33 patients, 13 elbows had a fracture in either condyle peri-operatively, and 27 elbows were intact. The fractured condyle was either fixed internally or excised. We found no statistical difference in the patients’ background, such as age, length of follow-up, immobilisation period, Larsen’s radiological grade, or Steinbrocker’s stage and functional class. There was also no statistical difference between the groups in relation to the Mayo Elbow Performance Score, muscle strength, range of movement, or radiolucency around the implants at a mean of 4.8 years (1.1 to 8.0) follow-up.

We conclude that fractured condyles can be successfully treated with either internal fixation or excision, and cause no harmful effect.
Conservative treatment of isolated fractures of the medial malleolus
Authors: Herscovici D. , Scaduto J. M. , Infante A.
Published: January 2007

Between 1992 and 2000, 57 patients with 57 isolated fractures of the medial malleolus were treated conservatively by immobilisation in a cast. The results were assessed by examination, radiography and completion of the short form-36 questionnaire and American Orthopaedic Foot and Ankle Society ankle-hindfoot score.

Of the 57 fractures 55 healed without further treatment. The mean combined dorsi- and plantar flexion was 52.3° (25° to 82°) and the mean short form-36 and American Orthopaedic Foot and Ankle Society scores 48.1 (28 to 60) and 89.8 (69 to 100), respectively. At review there was no evidence of medial instability, dermatological complications, malalignment of the mortise or of post-traumatic arthritis.

Isolated fractures of the medial malleolus can obtain high rates of union and good functional results with conservative treatment. Operation should be reserved for bi- or trimalleolar fractures, open fractures, injuries which compromise the skin or those involving the plafond or for patients who develop painful nonunion.
Treatment of osteonecrosis of the femoral head with hBMP-2-gene-modified tissue-engineered bone in goats
Authors: Tang T. T. , Lu B. , Yue B. , Xie X. H. , Xie Y. Z. , Dai K. R. , Lu J. X. , Lou J. R.
Published: January 2007

The efficacy of β-tricalcium phosphate (β-TCP) loaded with bone morphogenetic protein-2 (BMP-2)-gene-modified bone-marrow mesenchymal stem cells (BMSCs) was evaluated for the repair of experimentally-induced osteonecrosis of the femoral head in goats.

Bilateral early-stage osteonecrosis was induced in adult goats three weeks after ligation of the lateral and medial circumflex arteries and delivery of liquid nitrogen into the femoral head. After core decompression, porous β-TCP loaded with BMP-2 gene- or β-galactosidase (gal)-gene-transduced BMSCs was implanted into the left and right femoral heads, respectively. At 16 weeks after implantation, there was collapse of the femoral head in the untreated group but not in the BMP-2 or β-gal groups. The femoral heads in the BMP-2 group had a normal density and surface, while those in the β-gal group presented with a low density and an irregular surface. Histologically, new bone and fibrous tissue were formed in the macropores of the β-TCP. Sixteen weeks after implantation, lamellar bone had formed in the BMP-2 group, but there were some empty cavities and residual fibrous tissue in the β-gal group. The new bone volume in the BMP-2 group was significantly higher than that in the β-gal group. The maximum compressive strength and Young’s modulus of the repaired tissue in the BMP-2 group were similar to those of normal bone and significantly higher than those in the β-gal group.

Our findings indicate that porous β-TCP loaded with BMP-2-gene-transduced BMSCs are capable of repairing early-stage, experimentally-induced osteonecrosis of the femoral head and of restoring its mechanical function.
Reduction of the potential for thermal damage during hip resurfacing
Authors: Gill H. S. , Campbell P. A. , Murray D. W. , De Smet K. A.
Published: January 2007

Resurfacing arthroplasty of the hip is being used increasingly as an alternative to total hip replacement, especially for young active patients. There is concern about necrosis of the femoral head after resurfacing which can result in fracture and loosening. Most systems use a cemented femoral component, with the potential for thermal necrosis of the cancellous bone of the reamed femoral head. We used thermal probes to record temperatures close to the cement-bone interface during resurfacing arthroplasty.

The maximum temperature recorded at the cement-bone interface in four cases was approximately 68°C which was higher than that reported to kill osteocytes. A modified surgical technique using insertion of a suction cannula into the lesser trochanter, generous pulsed lavage and early reduction of the joint significantly reduced the maximum recorded cancellous bone temperature to approximately 36°C in five cases (p = 0.014).

We recommend the modified technique since it significantly reduces temperatures at the cement-bone interface.
A minimally-invasive technique for the treatment of pyogenic sacroiliitis
Authors: Giannoudis P. V. , Tsiridis E.
Published: January 2007

We report the management of an adult patient with septic sacroiliitis. This is an uncommon condition. Debridement, decompression and spontaneous fusion are the treatment of choice when symptoms do not resolve with routine initial intravenous antibiotic therapy. A percutaneous technique is described, using the principles of sacroiliac screw insertion commonly used for pelvic reconstruction surgery. After successful evacuation of the infected joint, fusion was observed in our patient.
A Homogeneous Assay for Analysis of FMR1 Promoter Methylation in Patients with Fragile X Syndrome
Authors: Dahl Christina , Grønskov Karen , Larsen Lars A , Guldberg Per , Brøndum-Nielsen Karen
Published: January 2007

Background: Fragile X syndrome is caused by the expansion of a CGG trinucleotide repeat at the 5′ untranslated region of the fragile X mental retardation 1 gene (FMR1). When expanded to >200 repeats (full mutation), the repeat region and the adjacent promoter CpG island become hypermethylated, rendering FMR1 transcriptionally inactive. Conventional molecular diagnosis of fragile X syndrome involves determination of the CGG repeat number by Southern blot analysis.

Methods: A homogeneous methylation-specific melting curve analysis (MS-MCA) assay for methylation status of the FMR1 promoter region was developed on the LightCycler platform. Genomic DNA was treated with sodium bisulfite, and a region containing 8 CpG sites was amplified in the presence of SYBR Green I, using primers that do not differentiate between methylated and unmethylated FMR1 molecules. After amplification, the samples were melted at 0.05 °C/s, and fluorescence melting curves were recorded. We studied samples, previously characterized by Southern blot analyses, from 10 female and 10 male donors with normal numbers of CGG trinucleotide repeats, 9 male donors who were premutation carriers, 4 male donors who carried both a premutation and a full mutation, and 25 patients with fragile X syndrome.

Results: Samples from all 20 male patients with fragile X syndrome showed a high melting peak corresponding to fully methylated FMR1, whereas samples from healthy males showed a single low melting peak corresponding to unmethylated FMR1. Of 24 samples from affected males, 9 (38%) showed 2 melting peaks, suggesting that cellular methylation mosaicism is common in fragile X syndrome.

Conclusions: MS-MCA allows rapid and reliable identification of fragile X syndrome in male patients.
Potential of Broussonetia papyrifera leaves as biomonitors for atmospheric pollution: use of INAA and AAS techniques
Authors: Daud Muhammad , Khalid Nasir , Iqbal J. , Ahmad Shujaat , Zaidi Jamshed H.
Published: January 2007

This study deals with the assessment of potential of Broussonetia papyrifera leaves as biomonitors of air pollution. The leaves samples were collected from urban areas, i.e., road sides with variable traffic load, industrial areas, as well as from a rural area as a reference site. Leaves samples have been analyzed for 34 elements using instrumental neutron activation analysis (INAA) in combination with atomic absorption spectrophotometry (AAS). The reliability of the methods used was established by analyzing reference materials (RMs) under identical experimental conditions and comparing the results obtained with the certified values, which are in quite good agreement with each other. The results obtained from different sites showed promising potential of this species as multi-elements environmental biomonitor due to their ability to reflect the levels of air pollution in the vicinity in which they grow.
Influence of Planting Date and Microsite on Weed Dynamics in Sugarcane in Sri Lanka
Authors: Witharama W. R. G. , Naylor Robert E. L. , Whytock G. P.
Published: January 2007

Experiments were conducted in Sri Lanka to compare weed seedling emergence in three sugarcane plots of 0.1 ha planted in October 1995, January 1996, and April 1996. In each plot, weed seedling emergence was monitored for 20 wk in five permanent quadrats on each of three microsites: on ridges, in furrows, and on adjacent fallow land. Soil moisture (0 to 5 cm) and soil temperature (at 2.5 cm) were also recorded. Only crowfootgrass, swamp millet, and guineagrass (all grasses) occurred in all nine planting time-by-microsite combinations. About half of all seedlings emerging over the three planting times were swamp millet, and the next most frequent species was tropic ageratum. The composition of the emerged flora was similar on ridges and in furrows, but more seedlings emerged in the furrows than on the ridges. The highest number of emerged seedlings and of species occurred on adjacent fallow land. The major factor influencing seedling emergence appeared to be soil moisture.
Formulation and Adjuvant Effects on Uptake and Translocation of Clethodim in Bermudagrass (Cynodon dactylon)
Authors: Nandula Vijay K. , Poston Daniel H. , Reddy Krishna N. , Koger Clifford H.
Published: January 2007

The effect of formulation and adjuvants on absorption and translocation of 14C-clethodim was determined at 1, 4, 12, 24, 48, and 72 h after treatment (HAT) in bermudagrass under greenhouse conditions. Absorption of 14C-clethodim with the 0.12 kg L−1 (15 to 85%) formulation was higher than with the 0.24 kg L−1 (5 to 40%) formulation, regardless of presence or absence of adjuvant. There was considerable variation in the effect of adjuvant on 14C-clethodim absorption. When either ammonium sulfate (AMS) or AMS plus crop oil concentrate (COC) was added to the 0.12 kg L−1 formulation, 14C-clethodim absorption increased significantly at all harvest times except at 12 HAT compared with 0.12 kg L−1 formulation alone, whereas, 14C-clethodim absorption after addition of COC to the 0.12 kg L−1 formulation was similar to the 0.12 kg L−1 formulation alone up to 24 HAT. Conversely, COC enhanced 14C-absorption at all harvest times when added to 0.24 kg L−1 formulation. Most of 14C-clethodim (79 to 100% of absorbed) remained in the treated leaf, independent of formulation or adjuvant. Formulation did not have an impact on distribution of absorbed 14C-clethodim; however, presence of an adjuvant increased movement of 14C-clethodim out of treated leaf. Of the absorbed 14C-label, most remained in the treated leaf. 14C-clethodim that translocated out of the treated leaf remained in the shoot, and negligible amount of 14C-clethodim translocated to roots. These results demonstrated improved absorption of clethodim with formulations containing half the active ingredient (0.12 kg L−1) and inclusion of both AMS and COC.
Volunteer Barley Interference in Spring Wheat Grown in a Zero-Tillage System
Authors: O'Donovan John T. , Neil Harker K. , Clayton George W. , Hall Linda M. , Cathcart Jason , Sapsford Kenneth L. , Holm F. A. , Hacault Kristin
Published: January 2007

There is no published information on the impact of volunteer barley on wheat yield loss or on the economics of controlling barley with a herbicide. With the registration of imazamox-resistant wheat, it is now possible to control volunteer barley in wheat. Thus, the likelihood of growing wheat in rotation with barley may increase. Field experiments were conducted in 2003 and 2004 at Beaverlodge, Lacombe, and Edmonton, AB, Canada, and Saskatoon, SK, Canada, to determine the impact of volunteer barley on yield of imazamox-resistant spring wheat seeded at relatively low (100 kg ha−1) and high (175 kg ha−1) rates. Barley was seeded at different densities to simulate volunteer barley infestations. Regression analysis indicated that wheat-plant density influenced the effects of volunteer barley interference on wheat yield loss, economic threshold values, and volunteer barley fecundity among locations and years. Economic thresholds varied from as few volunteer barley plants as 3 m−2at Beaverlodge in 2003 and 2004 to 48 m−2at Lacombe in 2003. In most cases, wheat yield loss and volunteer barley fecundity were lower and economic thresholds were higher when wheat was seeded at the higher rate. For example, averaged over both years at Beaverlodge initial slope values (percentage of wheat yield loss at low barley density) were 4.5 and 1.7%, and economic threshold values of volunteer barley plants were 3 m−2and 8 m−2at low and high wheat seeding rates, respectively. Results indicate that volunteer barley can be highly competitive in wheat, but yield losses and wheat seed contamination due to volunteer barley can be alleviated by seeding wheat at a relatively high rate.
Stability of Fluridone-Resistant Hydrilla (Hydrilla verticillata) Biotypes over Time
Authors: Puri Atul , MacDonald G. E. , Haller W. T.
Published: January 2007

Hydrilla is one of the most serious aquatic weed problems in the United States, and fluridone is the only herbicide approved by the U.S. Environment Protection Agency that provides systemic control. Recently, hydrilla biotypes with varying levels of fluridone resistance have been documented in Florida. Hydrilla biotypes of varying fluridone resistance levels were maintained in 900-L tanks under natural atmospheric conditions from September 2004 to September 2005 in the absence of fluridone. Hydrilla shoot tips were collected from each biotype during September 2004 (at planting), December 2004 (3 mo after planting [MAP]), March 2005 (6 MAP), June 2005 (9 MAP), and September 2005 (12 MAP) and exposed to 5, 10, 15, 20, 30, and 50 µg L−1fluridone to assess changes in susceptibility to this herbicide over time. Nonlinear regression analysis was used to calculate EC50values for phytoene and β-carotene (effective fluridone concentration to increase/decrease the phytoene/β-carotene content in hydrilla plant tissue by 50% over the untreated control) at each time interval. EC50values did not change in the susceptible hydrilla biotype over time. The EC50values for phytoene and β-carotene for the susceptible biotype were 7.5 and 8.9 µg L−1, respectively, at planting and 7.6 and 9.4 µg L−1, respectively, at 12 MAP. Resistant hydrilla biotypes (R1–R5) also showed no change in EC50phytoene values over time. Although, EC50β-carotene values in resistant biotypes R1, R3, R4, and R5 did not change over time, R2 recorded a reduction in EC50β-carotene at 12 MAP. Also, a 0.5-point decrease in resistance factor was observed for all resistant biotypes. Future long-term studies are needed to evaluate stability of resistant hydrilla biotypes in the absence of fluridone selection pressure.
Developmental Changes in Cardiomyocytes Differentiated from Human Embryonic Stem Cells: A Molecular and Electrophysiological Approach
Authors: Sartiani Laura , Bettiol Esther , Stillitano Francesca , Mugelli Alessandro , Cerbai Elisabetta , Jaconi Marisa E.
Published: January 2007

Cardiomyocytes derived from human embryonic stem cells constitute a promising cell source for the regeneration of damaged hearts. The assessment of their in vitro functional properties is mandatory to envisage appropriate cardiac cell-based therapies. In this study, we characterized human embryonic stem cell-derived cardiomyocytes over a 3-month period, using patch-clamp or intracellular recordings to assess their functional maturation and reverse transcriptase-polymerase chain reaction to evaluate the expression of ion channel-encoding subunits. Ito1 and IK1, the transient outward and inward rectifier potassium currents, were present in cardiomyocytes only, whereas the rapid delayed rectifier potassium current (IKr), pacemaker current (If), and L-type calcium current (ICa,L) could be recorded both in undifferentiated human embryonic stem cells and in cardiomyocytes. Most of the currents underwent developmental maturation in cardiomyocytes, as assessed by modifications in current density (Ito1, IK1, and ICa,L) and properties (If). Ion-channel mRNAs were always present when the current was recorded. Intracellular recordings in spontaneously beating clusters of cardiomyocytes revealed changes in action potential parameters and in response to pharmacological tools according to time of differentiation. In summary, human embryonic stem cell-derived cardiomyocytes mature over time during in vitro differentiation, approaching an adult phenotype.

Disclosure of potential conflicts of interest is found at the end of this article.
Differentiation of Human Embryonic Stem Cells into Corneal Epithelial-Like Cells by In Vitro Replication of the Corneal Epithelial Stem Cell Niche
Authors: Ahmad Sajjad , Stewart Rebecca , Yung Sun , Kolli Sai , Armstrong Lyle , Stojkovic Miodrag , Figueiredo Francisco , Lako Majlinda
Published: January 2007

Human embryonic stem cells (hESCs) are pluripotent cells capable of differentiating into any cell type of the body. It has long been known that the adult stem cell niche is vital for the maintenance of adult stem cells. The cornea at the front of the eye is covered by a stratified epithelium that is renewed by stem cells located at its periphery in a region known as the limbus. These so-called limbal stem cells are maintained by factors within the limbal microenvironment, including collagen IV in basement membrane and limbal fibroblasts in the stroma. Because this niche is very specific to the stem cells (rather than to the more differentiated cells) of the corneal epithelium, it was hypothesized that replication of these factors in vitro would result in hESC differentiation into corneal epithelial-like cells. Indeed, here we show that culturing of hESC on collagen IV using medium conditioned by the limbal fibroblasts results in the loss of pluripotency and differentiation into epithelial-like cells. Further differentiation results in the formation of terminally differentiated epithelial-like cells not only of the cornea but also of skin. Scanning electron microscopy shows that some differences exist between hESC-derived and adult limbal epithelial-like cells, necessitating further investigation using in vivo animal models of limbal stem cell deficiency. Such a model of hESC differentiation is useful for understanding the early events of epithelial lineage specification and to the eventual potential application of epithelium differentiated from hESC for clinical conditions of epithelial stem cell loss.

Disclosure of potential conflicts of interest is found at the end of this article.
Inductive mechanisms limiting response to anti-epidermal growth factor receptor therapy
Authors: Hutcheson Iain R , Knowlden Janice M , Jones Helen E , Burmi Rajpal S , McClelland Richard A , Barrow Denise , Gee Julia M W , Nicholson Robert I
Published: January 2007

Aberrant epidermal growth factor receptor (EGFR) signalling, a key feature of a variety of human malignancies, can drive a range of mechanisms underlying tumour growth and progression, including increased cell proliferation, angiogenesis, metastasis and decreased apoptosis. Anti-EGFR therapies, as monotherapies and in combination with chemotherapy, have proved effective in inhibiting these processes both in the clinical and in the preclinical settings. However, only a small cohort of patients have derived significant benefit from this therapy, with both de novo and acquired resistance to these agents evident in a number of recent studies. If we are to improve the effectiveness of such targeted therapies, then there is an urgent need to understand the resistance mechanisms. Here, we describe both non-genomic and genomic mechanisms of resistance to the selective EGFR tyrosine kinase inhibitor gefitinib (IRESSA), which we have identified initially in an EGFR-positive tamoxifen-resistant MCF-7 breast cancer cell line, but more recently in other EGFR-positive cancer types. Importantly, we show that gefitinib, in common with anti-hormonal agents, is not a passive bystander in the cellular response to drug treatment, but plays an active role in promoting signalling pathways that serve to limit its anti-tumour activity and maintain the cellular cohort from which acquired resistance can ultimately evolve. These findings indicate that inductive signalling is an important determinant of response to EGFR-targeted therapies and deciphering such pathways may provide us with the opportunity to design more effective strategies to combat resistance mechanisms and improve response to initial therapy.
Estrogen-related receptor α as a therapeutic target in cancer
Authors: Stein R A , McDonnell D P
Published: January 2007

The orphan receptor estrogen-related receptor α (ERRα) is a member of the nuclear receptor superfamily of ligand-regulated transcription factors. This protein is structurally most related to the canonical estrogen receptor and has been shown to modulate estrogen signaling in some contexts. These observations have heightened interest in ERRα as a therapeutic target in both breast and ovarian cancer and in other estrogenopathies. This review details our present understanding of ERRα action with a view to highlight specific aspects of its signal-transduction pathway in breast cancer that may be amenable to pharmaceutical manipulation.
Targeting of multiple signalling pathways by heat shock protein 90 molecular chaperone inhibitors
Authors: Powers Marissa V , Workman Paul
Published: January 2007

The last decade has seen the molecular chaperone heat shock protein 90 (HSP90) emerge as an exciting target for cancer therapy. This is because HSP90 is involved in maintaining the conformation, stability, activity and cellular localisation of several key oncogenic client proteins. These include, amongst others, ERBB2, C-RAF, CDK4, AKT/PKB, steroid hormone receptors, mutant p53, HIF-1α , survivin and telomerase hTERT. Therefore, modulation of this single drug target offers the prospect of simultaneously inhibiting all the multiple signalling pathways and biological processes that have been implicated in the development of the malignant phenotype. The chaperone function of HSP90 requires the formation of a multichaperone complex, which is dependent on the hydrolysis of ATP and ADP/ATP exchange. Most current inhibitors of HSP90 act as nucleotide mimetics, which block the intrinsic ATPase activity of this molecular chaperone. The first-in-class inhibitor to enter and complete phase I clinical trials was the geldanamycin analogue, 17-allylamino-17-demethoxygeldanamycin. The results of these trials have demonstrated that HSP90 is a valid drug target. Evidence of clinical activity has been seen in patients with melanoma, breast and prostate cancer. This article provides a personal perspective of the present efforts to increase our understanding of the molecular and cellular consequences of HSP90 inhibition, with examples from work in our own laboratory. We also review the discovery and development of novel small-molecule inhibitors and discuss alternative approaches to inhibit HSP90 activity, both of which offer exciting prospects for the future.
Best Management Practices for Nutrient and Sediment Retention in Urban Stormwater Runoff
Authors: Hogan Dianna M. , Walbridge Mark R.
Published: January 2007

Stormwater management infrastructure is utilized in urban areas to alleviate flooding caused by decreased landscape permeability from increased impervious surface cover (ISC) construction. In this study, we examined two types of stormwater detention basins, SDB‐BMPs (stormwater detention basin‐best management practice), and SDB‐FCs (stormwater detention basin–flood control). Both are constructed to retain peak stormwater flows for flood mitigation. However, the SDB‐BMPs are also designed using basin topography and wetland vegetation to provide water quality improvement (nutrient and sediment removal and retention). The objective of this study was to compare SDB (both SDB‐BMP and SDB‐FC) surface soil P concentrations, P saturation, and Fe chemistry with natural riparian wetlands (RWs), using sites in Fairfax County, Virginia as a model system. The SDB‐BMPs had significantly greater surface soil total P (Pt) concentrations than the RWs and SDB‐FCs (831.9 ± 32.5 kg ha−1, 643.3 ± 19.1 kg ha−1, and 652.1 ± 18.8 kg ha−1, respectively). The soil P sorption capacities of SDB‐BMPs were similar to the RWs, and were greater than those of SDB‐FCs, appearing to result in greater soil P removal and retention in SDB‐BMPs compared with SDB‐FCs. Increased Fe concentrations and relatively greater amounts of more crystalline forms of Fe in SDB‐BMP soils suggested increased sediment deposition compared with RW and SDB‐FC soils. Data suggest that SDB nutrient and sediment retention is facilitated in SDB‐BMPs. When stormwater management is necessary, use of SDB‐BMPs instead of SDB‐FCs could foster more responsible urban development and be an appropriate mitigation action for receiving aquatic ecosystems.
Economically Optimal Nitrogen Rate Reduces Soil Residual Nitrate
Authors: Hong Nan , Scharf Peter C. , Davis J. Glenn , Kitchen Newell R. , Sudduth Kenneth A.
Published: January 2007

Post‐harvest residual soil NO3–N (RSN) is susceptible to transfer to water resources. Practices that minimize RSN levels can reduce N loss to the environment. Our objectives were (i) to determine if the RSN after corn (Zea maysL.) harvest can be reduced if N fertilizer is applied at the economically optimal N rate (EONR) as compared to current producer practices in the midwestern USA and (ii) to compare RSN levels for N fertilizer rates below, at, and above the EONR. Six experiments were conducted in producer fields in three major soil areas (Mississippi Delta alluvial, deep loess, claypan) in Missouri over 2 yr. Predominant soil great groups were Albaqualfs, Argiudolls, Haplaquolls, and Fluvaquents. At four transects in each field, six treatment N rates from 0 to 280 kg N ha−1were applied, the EONR was determined, and the RSN was measured to a 0.9‐m depth from five treatment plots. The EONR at sampling sites varied from 49 to 228 kg N ha−1depending on site and year. Estimated average RSN at the EONR was 33 kg N ha−1in the 0.9‐m profile. This was at least 12 kg N ha−1lower than RSN at the producers' N rates. The RSN increased with increasing ΔEONR (total N applied − EONR). This relationship was best modeled by a plateau‐linear function, with a low RSN plateau at N rates well below the EONR. A linear increase in RSN began anywhere from 65 kg N ha−1below the EONR to 20 kg N ha−1above the EONR at the three sites with good data resolution near the EONR. Applying N rates in excess of the EONR produced elevated RSN values in all six experiments. Our results suggest that applying the EONR will produce environmental benefits in an economically sound manner, and that continued attempts to develop methods for accurately predicting EONR are justified.
A Molecular Fingerprint Technique to Detect Pollution‐Related Changes in River Cyanobacterial Diversity
Authors: Rodríguez Virginia , Aguirre de Cárcer Daniel , Loza Virginia , Perona Elvira , Mateo Pilar
Published: January 2007

Humans now have a strong influence on almost every major aquatic ecosystem, and our activities have dramatically altered the quality of receiving waters worldwide. Thus, there is a continuous need to develop and apply novel and effective technologies to detect, manage, and correct human‐induced degradation of aquatic systems. In the present work, we evaluated the molecular approach using polymerase chain reaction (PCR)‐temperature gradient gel electrophoresis (TGGE) to measure changes in cyanobacterial diversity along a pollution gradient in a river and compared it with that of using microscopic observations of field‐fixed and cultured samples. The different 16S rDNA genes present in the cyanobacterial community of each sampling point of the river were separated by TGGE, giving a characteristic pattern of bands for each site. This pattern represents a “fingerprint” of the community, allowing direct comparisons of the different samples. The TGGE results revealed that the structure of the cyanobacterial community differed along the pollution gradient of the river. Microscopic and molecular approaches showed that cyanobacterial diversity decreased in a downstream direction. Similar results were obtained by the two methods, as indicated by the high correlation between them. We suggest PCR‐TGGE could be a useful and rapidly applied technique for the routine analysis of changes in cyanobacterial diversity in response to pollution, which would allow us to monitor rivers in surveillance networks of watercourse quality.
Microbial Biomass Governs Enzyme Activity Decay during Aging of Worm‐Worked Substrates through Vermicomposting
Authors: Aira Manuel , Monroy Fernando , Domínguez Jorge
Published: January 2007

Vermicomposting is the biooxidation and stabilization of organic matter involving the joint action of earthworms and microorganisms, thereby turning wastes into a valuable soil amendment called vermicompost. Studies have focused on the changes in the type of substrates available before and after vermicomposting, but little is known on how these changes take place, especially those changes related with maturation of vermicompost. This study investigated the effects of aging on the microbiological properties of fresh vermicompost produced from pig slurry by analyzing the substrate after the earthworms had left it. We incubated 16‐wk‐old vermicompost and sampled it after 15, 30, 45, and 60 d analyzing microbial biomass and activity (assessed as microbial biomass N and basal respiration respectively) and four enzymatic activities (β‐glucosidase, cellulase, protease, and alkaline phosphatase). Aging of vermicompost resulted in decreases of microbial biomass and activity. Three of the four enzymes analyzed also showed decrease. An initial increase followed by a rapid decrease in alkaline phosphatase was also recorded. High and significant correlations between microbial biomass and β‐glucosidase (r = 0.62, P < 0.001), cellulase (r = 0.56, P < 0.01), and protease (r = 0.82, P < 0.001) were found. Results suggest that there may be two steps involved in the aging dynamics of vermicompost with regards to extracellular enzyme activity; the first step was characterized by a decrease in microbial populations, which resulted in a reduction in the synthesis of new enzymes. The second step was the degradation of the pool of remaining enzymes. This dynamic does not seem to be affected by earthworms because similar decaying patterns of microbial biomass and activity were found in substrate where earthworms were present.
Effect of Dissolved Organic Carbon on Zinc Solubility in Incubated Biosolids‐Amended Soils
Authors: Antoniadis Vasileios , Tsadilas Christos D. , Stamatiadis Stamatis
Published: January 2007

Soil organic carbon (SOC) and dissolved organic carbon (DOC) affect long‐term heavy metal solubility in biosolids‐amended soils, but their role needs to be further studied under Mediterranean climatic conditions. We investigated Zn solubility, as assessed by water extraction, in two typical Greek soils amended with biosolids at 0, 20, and 100 Mg ha−1during a 310‐d incubation period. It was found that SOC decreased by nearly 30% over time in the 100 Mg ha−1treatment. There was evidence that DOC affected Zn solubility, because DOC increased significantly on Day 23, probably due to a flush in microbial activity, and water‐extractable Zn followed the same trend. After that, both DOC and water‐extractable Zn decreased back to values similar to those of the unamended soils. Although Zn solubility did not increase overall even at high biosolids application rates, this study shows that time‐limited fluctuations in Zn solubility due to sudden DOC flushes, can be significant, and need to be further investigated.