bluuebunny/crossref_metadata_2025_split huggingface dataset:
The migration of paraxial and lateral plate mesoderm cells emerging from the late primitive streak is controlled by different Wnt signals
Authors: Sweetman Dylan , Wagstaff Laura , Cooper Oliver , Weijer Cornelis , Münsterberg Andrea 
Published: June 2008

Abstract

Background
Co-ordinated cell movement is a fundamental feature of developing embryos. Massive cell movements occur during vertebrate gastrulation and during the subsequent extension of the embryonic body axis. These are controlled by cell-cell signalling and a number of pathways have been implicated. Here we use long-term video microscopy in chicken embryos to visualize the migration routes and movement behaviour of mesoderm progenitor cells as they emerge from the primitive streak (PS) between HH stages 7 and 10.

Results
We observed distinct cell movement behaviours along the length of the streak and determined that this is position dependent with cells responding to environmental cues. The behaviour of cells was altered by exposing embryos or primitive streak explants to cell pellets expressing Wnt3a and Wnt5a, without affecting cell fates, thus implicating these ligands in the regulation of cell movement behaviour. Interestingly younger embryos were not responsive, suggesting that Wnt3a and Wnt5a are specifically involved in the generation of posterior mesoderm, consistent with existing mouse and zebrafish mutants. To investigate which downstream components are involved mutant forms of dishevelled (dsh) and prickle1 (pk1) were electroporated into the primitive streak. These had differential effects on the behaviour of mesoderm progenitors emerging from anterior or posterior regions of the streak, suggesting that multiple Wnt pathways are involved in controlling cell migration during extension of the body axis in amniote embryos.

Conclusion
We suggest that the distinct behaviours of paraxial and lateral mesoderm precursors are regulated by the opposing actions of Wnt5a and Wnt3a as they leave the primitive streak in neurula stage embryos. Our data suggests that Wnt5a acts via prickle to cause migration of cells from the posterior streak. In the anterior streak, this is antagonised by Wnt3a to generate non-migratory medial mesoderm.
atonal- and achaete-scute-related genes in the annelid Platynereis dumerilii: insights into the evolution of neural basic-Helix-Loop-Helix genes
Authors: Simionato Elena , Kerner Pierre , Dray Nicolas , Le Gouar Martine , Ledent Valérie , Arendt Detlev , Vervoort Michel 
Published: June 2008

AbstractBackgroundFunctional studies in model organisms, such as vertebrates andDrosophila, have shown that basic Helix-loop-Helix (bHLH) proteins have important roles in different steps of neurogenesis, from the acquisition of neural fate to the differentiation into specific neural cell types. However, these studies highlighted many differences in the expression and function of orthologous bHLH proteins during neural development between vertebrates andDrosophila. To understand how the functions of neural bHLH genes have evolved among bilaterians, we have performed a detailed study of bHLH genes during nervous system development in the polychaete annelid,Platynereis dumerilii, an organism which is evolutionary distant from bothDrosophilaand vertebrates.ResultsWe have studiedPlatynereisorthologs of the most important vertebrate neural bHLH genes, i.e.achaete-scute, neurogenin, atonal, olig, andNeuroDgenes, the latter two being genes absent of theDrosophilagenome. We observed that all these genes have specific expression patterns during nervous system formation inPlatynereis. Our data suggest that inPlatynereis, like in vertebrates but unlikeDrosophila, (i)neurogeninis the main proneural gene for the formation of the trunk central nervous system, (ii)achaete-scuteandoliggenes are involved in neural subtype specification in the central nervous system, in particular in the specification of the serotonergic phenotype. In addition, we found that thePlatynereis NeuroDgene has a broad and early neuroectodermal expression, which is completely different from the neuronal expression of vertebrateNeuroDgenes.ConclusionOur analysis suggests that thePlatynereisbHLH genes have both proneural and neuronal specification functions, in a way more akin to the vertebrate situation than to that ofDrosophila. We conclude that these features are ancestral to bilaterians and have been conserved in the vertebrates and annelids lineages, but have diverged in the evolutionary lineage leading toDrosophila.
A simple and accurate SNP scoring strategy based on typeIIS restriction endonuclease cleavage and matrix-assisted laser desorption/ionization mass spectrometry
Authors: Hong Sun Pyo , Ji Seung Il , Rhee Hwanseok , Shin Soo Kyeong , Hwang Sun Young , Lee Seung Hwan , Lee Soong Deok , Oh Heung-Bum , Yoo Wangdon , Kim Soo-Ok 
Published: June 2008

Abstract

Background
We describe the development of a novel matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF)-based single nucleotide polymorphism (SNP) scoring strategy, termed Restriction Fragment Mass Polymorphism (RFMP) that is suitable for genotyping variations in a simple, accurate, and high-throughput manner. The assay is based on polymerase chain reaction (PCR) amplification and mass measurement of oligonucleotides containing a polymorphic base, to which a typeIIS restriction endonuclease recognition was introduced by PCR amplification. Enzymatic cleavage of the products leads to excision of oligonucleotide fragments representing base variation of the polymorphic site whose masses were determined by MALDI-TOF MS.

Results
The assay represents an improvement over previous methods because it relies on the direct mass determination of PCR products rather than on an indirect analysis, where a base-extended or fluorescent report tag is interpreted. The RFMP strategy is simple and straightforward, requiring one restriction digestion reaction following target amplification in a single vessel. With this technology, genotypes are generated with a high call rate (99.6%) and high accuracy (99.8%) as determined by independent sequencing.

Conclusion
The simplicity, accuracy and amenability to high-throughput screening analysis should make the RFMP assay suitable for large-scale genotype association study as well as clinical genotyping in laboratories.
CRISTOPH – A cluster-randomised intervention study to optimise the treatment of patients with hypertension in General Practice
Authors: Mortsiefer Achim , Meysen Tobias , Schumacher Martin , Lintges Claudia , Stamer Maren , Schmacke Norbert , Wegscheider Karl , Abholz Heinz-Harald , in der Schmitten Jürgen 
Published: June 2008

AbstractBackgroundRecent guidelines for the management of hypertension focus on treating patients according to their global cardiovascular risk (CVR), rather than strictly keeping blood pressure, or other risk factors, below set limit values. The objective of this study is to compare the effect of a simple versus a complex educational intervention implementing this new concept among General Practitioners (GPs).Methods/designA prospective longitudinal cluster-randomised intervention trial with 94 German GPs consecutively enroling 40 patients each with known hypertension. All GPs then received a written manual specifically developed to transfer the global concept of CVR into daily General Practice. After cluster-randomisation, half of the GPs additionally received a clinical outreach visit, with a trained peer discussing with them the concept of global CVR referring to example study patients from the respective GP. Main outcome measure is the improvement of calculated CVR six months after intervention in the subgroup of patients with high CVR (but no history of cardiovascular disease), defined as 10-year-mortality ≥ 5% employing the European SCORE formula. Secondary outcome measures include the intervention's effect on single risk factors, and on prescription rates of drugs targeting CVR. All outcome measures are separately studied in the three subgroups of patients with 1. high CVR (defined as above), 2. low CVR (SCORE < 5%), and 3. a history of cardiovascular disease. The influence of age, sex, social status, and the perceived quality of the respective doctor-patient-relation on the effects will be examined.DiscussionTo our knowledge, no other published intervention study has yet evaluated the impact of educating GPs with the goal to treat patients with hypertension according to their global cardiovascular risk.Trial registrationISRCTN44478543
Utility of 18F-fluoro-deoxyglucose emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in combination with ultrasonography for axillary staging in primary breast cancer
Authors: Ueda Shigeto , Tsuda Hitoshi , Asakawa Hideki , Omata Jiro , Fukatsu Kazuhiko , Kondo Nobuo , Kondo Tadaharu , Hama Yukihiro , Tamura Katsumi , Ishida Jiro , Abe Yoshiyuki , Mochizuki Hidetaka 
Published: June 2008

Abstract

Background
Accurate evaluation of axillary lymph node (ALN) involvement is mandatory before treatment of primary breast cancer. The aim of this study is to compare preoperative diagnostic accuracy between positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT) and axillary ultrasonography (AUS) for detecting ALN metastasis in patients having operable breast cancer, and to assess the clinical management of axillary 18F-FDG PET/CT for therapeutic indication of sentinel node biopsy (SNB) and preoperative systemic chemotherapy (PSC).

Methods
One hundred eighty-three patients with primary operable breast cancer were recruited. All patients underwent 18F-FDG PET/CT and AUS followed by SNB and/or ALN dissection (ALND). Using 18F-FDG PET/CT, we studied both a visual assessment of 18F-FDG uptake and standardized uptake value (SUV) for axillary staging.

Results
In a visual assessment of 18F-FDG PET/CT, the diagnostic accuracy of ALN metastasis was 83% with 58% in sensitivity and 95% in specificity, and when cut-off point of SUV was set at 1.8, sensitivity, specificity, and accuracy were 36, 100, and 79%, respectively. On the other hand, the diagnostic accuracy of AUS was 85% with 54% in sensitivity and 99% in specificity. By the combination of 18F-FDG PET/CT and AUS to the axilla, the sensitivity, specificity, and accuracy were 64, 94, and 85%, respectively. If either 18F-FDG PET uptake or AUS was positive in allixa, the probability of axillary metastasis was high; 50% (6 of 12) in 18F-FDG PET uptake only, 80% (4 of 5) in AUS positive only, and 100% (28 of 28) in dual positive. By the combination of AUS and 18F-FDG PET/CT, candidates of SNB were more appropriately selected. The axillary 18F-FDG uptake was correlated with the maximum size and nuclear grade of metastatic foci (p = 0.006 and p = 0.03).

Conclusion
The diagnostic accuracy of 18F-FDG PET/CT was shown to be nearly equal to ultrasound, and considering their limited sensitivities, the high radiation exposure by 18F-FDG PET/CT and also costs of the examination, it is likely that AUS will be more cost-effective in detecting massive axillary tumor burden. However, when we cannot judge the axillary staging using AUS alone, metabolic approach of 18F-FDG PET/CT for axillary staging would enable us a much more confident diagnosis.
Intravenous postoperative fluid prescriptions for children: A survey of practice
Authors: Davies Polly , Hall Tim , Ali Tariq , Lakhoo Kokila 
Published: June 2008

AbstractBackgroundPostoperative deaths and neurological injury have resulted from hyponatraemia associated with the use of hypotonic saline solutions following surgery. We aimed to determine the rates and types of intravenous fluids being prescribed postoperatively for children in the UK.MethodsA questionnaire was sent to members of the British Association of Paediatric Surgeons (BAPS) and Association of Paediatric Anaesthetists of Great Britain and Ireland (APAGBI) based at UK paediatric centres. Respondents were asked to prescribe postoperative fluids for scenarios involving children of different ages. The study period was between May 2006 and November 2006.ResultsThe most frequently used solution was sodium chloride 0.45% with glucose 5% although one quarter of respondents still used sodium chloride 0.18% with glucose 4%. Isotonic fluids were used by 41% of anaesthetists and 9.8% of surgeons for the older child, but fewer for infants. Standard maintenance rates or greater were prescribed by over 80% of respondents.ConclusionMost doctors said they would prescribe hypotonic fluids at volumes equal to or greater than traditional maintenance rates at the time of the survey. A survey to describe practice since publication of National Patient Safety Agency (NPSA) recommendations is required.
ret/PTC-1 expression alters the immunoprofile of thyroid follicular cells
Authors: Denning Karen , Smyth Paul , Cahill Susanne , Li Jinghuan , Flavin Richard , Aherne Sinead , O' Leary John J , Sheils Orla 
Published: June 2008

Abstract

Background
Hashimoto Thyroiditis (H.T.) is a destructive autoimmune thyroid condition whose precise molecular pathogenesis remains unclear. ret/PTC-1 is a chimeric transcript which has been described in autoimmune thyroid disease (AITD) and thyroid neoplasia. The purpose of this study was to observe the immunogenic effect exposure to H.T. and control lymphocyte supernatant would have on normal (Nthy-ori) and ret/PTC-1 (TPC-1) expressing thyroid cell line models.

Results
A 2 × 2 matrix comprising Nthy-ori and TPC-1 cell lines and H.T. and control lymphocyte supernatant was designed and utilised as follows; activated lymphocytic supernatant from a H.T. and normal control were co-cultured with a cell line derived from normal thyroid (Nthy-ori) and also a cell line derived from a papillary thyroid carcinoma that endogenously expresses ret/PTC-1 (TPC-1). The co-cultures were harvested at 0, 6 and 18 hour time points. Gene expression analysis was performed on RNA extracted from thyrocytes using TaqMan® Immune profiling Low-Density Arrays (Applied Biosystems, CA, USA) comprising gene expression markers for 93 immune related targets plus 3 endogenous controls.
Stimulation of the normal thyroid cell line model with activated T cell supernatant from the H.T. donor yielded global up-regulation of immune targets when compared with control supernatant stimulation. In particular, a cohort of targets (granzyme B, CD3, CD25, CD152, CD45) associated with cytotoxic cell death; T cell receptor (TCR) and T cell signaling were up-regulated in the normal cell line model. When the ret/PTC-1 expressing thyroid cell line was co-cultured with H.T. lymphocyte supernatant, in comparison to control supernatant stimulation, down-regulation of the same subset of immune targets was seen.

Conclusion
Co-culturing H.T. lymphocyte supernatant with a normal thyroid cell line model leads to over-expression of a subset of targets which could contribute to the pathogenesis of H.T. via cytotoxic cell death and TCR signalling. Stimulation of the ret/PTC-1 positive cell line with the same stimulus led to a down-regulated shift in the gene expression pattern of the cohort of immune targets. We hypothesize that ret/PTC-1 activation may dampen immunogenic responses in the thyroid, which could possibly facilitate papillary thyroid carcinoma development.
Stabilizing mutation of CTNNB1/beta-catenin and protein accumulation analyzed in a large series of parathyroid tumors of Swedish patients
Authors: Björklund Peyman , Lindberg Daniel , Åkerström Göran , Westin Gunnar 
Published: June 2008

Abstract

Background
Aberrant accumulation of β-catenin plays an important role in a variety of human neoplasms. We recently reported accumulation of β-catenin in parathyroid adenomas from patients with primary hyperparathyroidism (pHPT). In CTNNB1 exon 3, we detected a stabilizing mutation (S37A) in 3 out of 20 analyzed adenomas. The aim of the present study was to determine the frequency and zygosity of mutations in CTNNB1 exon 3, and β-catenin accumulation in a large series of parathyroid adenomas of Swedish patients.

Results
The mutation S37A (TCT > GCT) was detected by direct DNA sequencing of PCR fragments in 6 out of 104 sporadic parathyroid adenomas (5.8%). Taking our previous study into account, a total of 9 out of 124 (7.3%) adenomas displayed the same mutation. The mutations were homozygous by DNA sequencing, restriction enzyme cleavage, and gene copy number determination using the GeneChip 500 K Mapping Array Set. All tumors analyzed by immunohistochemistry, including those with mutation, displayed aberrant β-catenin accumulation. Western blotting revealed a slightly higher expression level of β-catenin and nonphosphorylated active β-catenin in tumors with mutation compared to those without. Presence of the mutation was not related to distinct clinical characteristics.

Conclusion
Aberrant accumulation of β-catenin is very common in parathyroid tumors, and is caused by stabilizing homozygous mutation in 7.3% of Swedish pHPT patients.
Nutritional skewing of conceptus sex in sheep: effects of a maternal diet enriched in rumen-protected polyunsaturated fatty acids (PUFA)
Authors: Green Mark P , Spate Lee D , Parks Tina E , Kimura Koji , Murphy Clifton N , Williams Jim E , Kerley Monty S , Green Jonathan A , Keisler Duane H , Roberts R Michael 
Published: June 2008

Abstract

Background
Evolutionary theory suggests that in polygynous mammalian species females in better body condition should produce more sons than daughters. Few controlled studies have however tested this hypothesis and controversy exists as to whether body condition score or maternal diet is in fact the determining factor of offspring sex. Here, we examined whether maternal diet, specifically increased n-6 polyunsaturated fatty acid (PUFA) intake, of ewes with a constant body condition score around the time of conception influenced sex ratio.

Methods
Ewes (n = 44) maintained in similar body condition throughout the study were assigned either a control (C) diet or one (F) enriched in rumen-protected PUFA, but otherwise essentially equivalent, from four weeks prior to breeding until d13 post-estrus. On d13, conceptuses were recovered, measured, cultured to assess their capacity for interferon-tau (IFNT) production and their sex determined. The experiment was repeated with all ewes being fed the F diet to remove any effects of parity order on sex ratio. Maternal body condition score (BCS), plasma hormone and metabolite concentrations were also assessed throughout the study and related to diet.

Results
In total 129 conceptuses were recovered. Ewes on the F diet produced significantly more male than female conceptuses (proportion male = 0.69; deviation from expected ratio of 0.5, P < 0.001). Conceptus IFNT production was unaffected by diet (P > 0.1), but positively correlated with maternal body condition score (P < 0.05), and was higher (P < 0.05) in female than male conceptuses after 4 h culture. Maternal plasma hormone and metabolite concentrations, especially progesterone and fatty acid, were also modulated by diet.

Conclusion
These results provide evidence that maternal diet, in the form of increased amounts of rumen-protected PUFA fed around conception, rather than maternal body condition, can skew the sex ratio towards males. These observations may have implications to the livestock industry and animal management policies when offspring of one sex may be preferred over the other.
A subgroup of plant aquaporins facilitate the bi-directional diffusion of As(OH)3 and Sb(OH)3across membranes
Authors: Bienert Gerd P , Thorsen Michael , Schüssler Manuela D , Nilsson Henrik R , Wagner Annemarie , Tamás Markus J , Jahn Thomas P 
Published: June 2008

Abstract

Background

Arsenic is a toxic and highly abundant metalloid that endangers human health through drinking water and the food chain. The most common forms of arsenic in the environment are arsenate (As(V)) and arsenite (As(III)). As(V) is a non-functional phosphate analog that enters the food chain via plant phosphate transporters. Inside cells, As(V) becomes reduced to As(III) for subsequent extrusion or compartmentation. Although much is known about As(III) transport and handling in microbes and mammals, the transport systems for As(III) have not yet been characterized in plants.

Results

Here we show that the Nodulin26-like Intrinsic Proteins (NIPs) AtNIP5;1 and AtNIP6;1 from Arabidopsis thaliana, OsNIP2;1 and OsNIP3;2 from Oryza sativa, and LjNIP5;1 and LjNIP6;1 from Lotus japonicus are bi-directional As(III) channels. Expression of these NIPs sensitized yeast cells to As(III) and antimonite (Sb(III)), and direct transport assays confirmed their ability to facilitate As(III) transport across cell membranes. On medium containing As(V), expression of the same NIPs improved yeast growth, probably due to increased As(III) efflux. Our data furthermore provide evidence that NIPs can discriminate between highly similar substrates and that they may have differential preferences in the direction of transport. A subgroup of As(III) permeable channels that group together in a phylogenetic tree required N-terminal truncation for functional expression in yeast.

Conclusion

This is the first molecular identification of plant As(III) transport systems and we propose that metalloid transport through NIPs is a conserved and ancient feature. Our observations are potentially of great importance for improved remediation and tolerance of plants, and may provide a key to the development of low arsenic crops for food production.
Expression of parathyroid hormone-related protein during immortalization of human peripheral blood mononuclear cells by HTLV-1: Implications for transformation
Authors: Nadella Murali VP , Shu Sherry T , Dirksen Wessel P , Thudi Nanda K , Nadella Kiran S , Fernandez Soledad A , Lairmore Michael D , Green Patrick L , Rosol Thomas J 
Published: June 2008

Abstract

Background
Adult T-cell leukemia/lymphoma (ATLL) is initiated by infection with human T-lymphotropic virus type-1 (HTLV-1); however, additional host factors are also required for T-cell transformation and development of ATLL. The HTLV-1 Tax protein plays an important role in the transformation of T-cells although the exact mechanisms remain unclear. Parathyroid hormone-related protein (PTHrP) plays an important role in the pathogenesis of humoral hypercalcemia of malignancy (HHM) that occurs in the majority of ATLL patients. However, PTHrP is also up-regulated in HTLV-1-carriers and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients without hypercalcemia, indicating that PTHrP is expressed before transformation of T-cells. The expression of PTHrP and the PTH/PTHrP receptor during immortalization or transformation of lymphocytes by HTLV-1 has not been investigated.

Results
We report that PTHrP was up-regulated during immortalization of lymphocytes from peripheral blood mononuclear cells by HTLV-1 infection in long-term co-culture assays. There was preferential utilization of the PTHrP-P2 promoter in the immortalized cells compared to the HTLV-1-transformed MT-2 cells. PTHrP expression did not correlate temporally with expression of HTLV-1 tax. HTLV-1 infection up-regulated the PTHrP receptor (PTH1R) in lymphocytes indicating a potential autocrine role for PTHrP. Furthermore, co-transfection of HTLV-1 expression plasmids and PTHrP P2/P3-promoter luciferase reporter plasmids demonstrated that HTLV-1 up-regulated PTHrP expression only mildly, indicating that other cellular factors and/or events are required for the very high PTHrP expression observed in ATLL cells. We also report that macrophage inflammatory protein-1α (MIP-1α), a cellular gene known to play an important role in the pathogenesis of HHM in ATLL patients, was highly expressed during early HTLV-1 infection indicating that, unlike PTHrP, its expression was enhanced due to activation of lymphocytes by HTLV-1 infection.

Conclusion
These data demonstrate that PTHrP and its receptor are up-regulated specifically during immortalization of T-lymphocytes by HTLV-1 infection and may facilitate the transformation process.