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Prime Candidate (prime + candidate)
Selected AbstractsSef is synexpressed with FGFs during chick embryogenesis and its expression is differentially regulated by FGFs in the developing limbDEVELOPMENTAL DYNAMICS, Issue 2 2005Haggar Harduf Abstract The signaling pathways leading to growth and patterning of various organs are tightly controlled during the development of any organism. These control mechanisms usually involve the utilization of feedback- and pathway-specific antagonists where the pathway induces the expression of its own antagonist. Sef is a feedback antagonist of fibroblast growth factor (FGF) signaling, which has been identified recently in zebrafish and mammals. Here, we report the isolation of chicken Sef (cSef) and demonstrate the conserved nature of the regulatory relationship with FGF signaling. In chick embryos, Sef is expressed in a pattern that coincides with many known sites of FGF signaling. In the developing limb, cSef is expressed in the mesoderm underlying the apical ectodermal ridge (AER) in the region known as the progress zone. cSef message first appeared after limb budding and AER formation. Expression was intense at stages of rapid limb outgrowth, and gradually decreased to almost undetectable levels when differentiation was clearly apparent. Gain- and loss-of-function experiments showed that FGFs differentially regulate the expression of cSef in various tissues. Thus, removal of the AER down-regulated cSef expression, and FGF2 but not FGF4 or FGF8 beads substituted for the AER in maintaining cSef expression. At sites where cSef is not normally expressed, FGF4 and FGF2, but not FGF8 beads, induced cSef expression. Our results demonstrate the complexity of cSef regulation by FGFs and point to FGF2 as a prime candidate in regulating cSef expression during normal limb development. The spatiotemporal pattern of cSef expression during limb development suggests a role for cSef in regulating limb outgrowth but not limb initiation. Developmental Dynamics 233:301,312, 2005. © 2005 Wiley-Liss, Inc. [source] Comparative analysis of the self-incompatibility (S -) locus region of Prunus mume: identification of a pollen-expressed F-box gene with allelic diversityGENES TO CELLS, Issue 3 2003Tetsuyuki Entani Background: Self-incompatibility (SI) in the Solanaceae, Rosaceae and Scrophulariaceae is gametophytically controlled by a single polymorphic locus, termed the S -locus. To date, the only known S -locus product is a polymorphic ribonuclease, termed S -RNase, which is secreted by stylar tissue and thought to act as a cytotoxin that degrades the RNA of incompatible pollen tubes. However, understanding how S -RNase causes S -haplotype specific inhibition of pollen tubes has been hampered by the lack of a cloned pollen S -determinant gene. Results: To identify the pollen S -determinant gene, we investigated the genomic structure of the S -locus region of the S1 - and S7 -haplotypes of Prunus mume (Japanese apricot), and identified 13 genes around the S-RNase gene. Among them, only one F-box gene, termed SLF (S -locus F-box), fulfilled the conditions for a pollen S -determinant gene: (i) together with the S-RNase gene, it is located within the highly divergent genomic region of the S -locus, (ii) it exhibits S -haplotype specific diversity among three analysed S -haplotypes, and (iii) it is specifically expressed in pollen, but not in the styles or leaves. Conclusion: The results indicate that SLF is a prime candidate for the pollen S -determinant gene of SI. [source] Role of Chronic Infection and Inflammation in the Gastrointestinal Tract in the Etiology and Pathogenesis of Idiopathic ParkinsonismHELICOBACTER, Issue 4 2005Part 1: Eradication of Helicobacter in the Cachexia of Idiopathic Parkinsonism ABSTRACT Background., Neuronal damage in idiopathic parkinsonism may be in response to ubiquitous occult infection. Since peptic ulceration is prodromal, Helicobacter is a prime candidate. Aim., To consider the candidature of Helicobacter in parkinsonism with cachexia. Methods., We explore the relationship between being underweight and inflammatory products in 124 subjects with idiopathic parkinsonism and 195 controls, and present the first case-series evidence of efficacy of Helicobacter eradication, in parkinsonism advanced to the stage of cachexia. Results., Association of a low body mass index with circulating interleukin-6 was specific to parkinsonism (p = .002), unlike that with antibodies against Helicobacter vacuolating-toxin and cytotoxicity-associated gene product (p < .04). Marked reversibility in both cachexia and disability of idiopathic parkinsonism followed Helicobacter heilmannii eradication in one case, Helicobacter pylori eradication in another, follow-up being , 3.5 years. The latter presented with postprandial bloating, and persistent nausea: following eradication, radioisotope gastric-emptying returned towards normal, and upper abdominal symptoms regressed. Reversibility of their cachexia/disability contrasts with the outcome of anti- Helicobacter therapy where eradication repeatedly failed (one case), and in non- Helicobacter gastritis (three cases). Anti-parkinsonian medication remained constant. Intestinal absorption and barrier function were normal in all. Conclusion., Categorization, according to presence or absence of Helicobacter infection, was a useful therapeutic tool in late idiopathic parkinsonism. [source] Theoretical Prediction of Post-Spinel Phases of Silicon NitrideJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 1 2002Kazuyoshi Tatsumi New phases of Si3N4 that may be stable at higher pressure than spinel have been searched using a first-principles plane-wave pseudopotential method. The CaTi2O4 -type phase is found to be the prime candidate for the post-spinel phase among six phases selected on the analogy to high-pressure oxides. The phase transformation from the spinel is predicted to occur at 210 GPa. All silicon atoms of the new phase are coordinated by six anions, similar to the case of the high-pressure forms of SiO2 and SiC. Because of its high energy at zero pressure, this new phase may be difficult to quench. The bandgap increases with an increase of pressure when compared in the same polymorph. However, the bandgap and the net charge decrease in the order of ,, spinel, and CaTi2O4 -type phases at zero pressure. The theoretical bulk modulus of the CaTi2O4 -type phase is comparable with that of spinel. [source] Stable expression of AtGA2ox1 in a low-input turfgrass (Paspalum notatum Flugge) reduces bioactive gibberellin levels and improves turf quality under field conditionsPLANT BIOTECHNOLOGY JOURNAL, Issue 6 2007Mrinalini Agharkar Summary Bahiagrass (Paspalum notatum Flugge) is a prime candidate for molecular improvement of turf quality. Its persistence and low input characteristics made it the dominant utility turfgrass along highways in the south-eastern USA. However, the comparatively poor turf quality due to reduced turf density and prolific production of unsightly inflorescences currently limits the widespread use of bahiagrass as residential turf. Alteration of endogenous gibberellin (GA) levels by application of growth regulators or transgenic strategies has modified plant architecture in several crops. GA catabolizing AtGA2ox1 was subcloned under the control of the constitutive maize ubiquitin promoter and Nos 3'UTR. A minimal AtGA2ox1 expression cassette lacking vector backbone sequences was stably introduced into apomictic bahiagrass by biolistic gene transfer as confirmed by Southern blot analysis. Expression of AtGA2ox1 in bahiagrass as indicated by reverse transcription,polymerase chain reaction and Northern blot analysis resulted in a significant reduction of endogenous bioactive GA1 levels compared to wild type. Interestingly, transgenic plants displayed an increased number of vegetative tillers which correlated with the level of AtGA2ox1 expression and enhanced turf density under field conditions. This indicates that GAs contribute to signalling the outgrowth of axillary buds in this perennial grass. Transgenic plants also showed decreased stem length and delayed flowering under controlled environment and field conditions. Consequently, turf quality following weekly mowing was improved in transgenic bahiagrass. Transgene expression and phenotype were transmitted to seed progeny. Argentine bahiagrass produces seeds asexually by apomixis, which reduces the risk of unintended transgene dispersal by pollen and results in uniform progeny. [source] Prader,Willi syndrome and Angelman syndrome,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2010Karin Buiting Abstract Prader,Willi syndrome (PWS) and Angelman syndrome (AS) are two distinct neurogenetic disorders in which imprinted genes on the proximal long arm of chromosome 15 are affected. Although the SNORD116 gene cluster has become a prime candidate for PWS, it cannot be excluded that other paternally expressed genes in the chromosomal region 15q11q13 contribute to the full phenotype. AS is caused by a deficiency of the UBE3A gene, which in the brain is expressed from the maternal allele only. The most frequent genetic lesions in both disorders are a de novo deletion of the chromosomal region 15q11q13, uniparental disomy 15, an imprinting defect or, in the case of AS, a mutation of the UBE3A gene. Microdeletions in a small number of patients with PWS and AS have led to the identification of the chromosome 15 imprinting center (IC). The IC consists of two critical elements, which act in cis to regulate imprinting in the whole chromosome 15q11q13 imprinted domain. © 2010 Wiley-Liss, Inc. [source] The dual role of Fas-ligand as an injury effector and defense strategy in diabetes and islet transplantation,BIOESSAYS, Issue 2 2006Michal Pearl-Yafe The exact process that leads to the eruption of autoimmune reactions against , cells and the evolution of diabetes is not fully understood. Macrophages and T cells may launch an initial immune reaction against the pancreatic islets of Langerhans, provoking inflammation and destructive insulitis. The information on the molecular mechanisms of the emergence of , cell injury is controversial and points to possibly important roles for the perforin,granzyme, Fas,Fas-ligand (FasL) and tumor-necrosis-factor-mediated apoptotic pathways. FasL has several unique features that make it a potentially ideal immunomodulatory tool. Most important, FasL is selectively toxic to cytotoxic T cells and less harmful to regulatory T cells. This review discusses the intrinsic sensitivity of , cells to FasL-mediated apoptosis, the conditions that underlie this , cell sensitivity, and the feasibility of using FasL to arrest autoimmunity and prevent islet allograft rejection. In both the autoimmune and transplant settings, it is imperative to progress from the administration of nonspecific immunosuppressive therapy to the concept of ,-cell-specific immunomodulation. FasL evolves as a prime candidate for antigen-specific immunomodulation. BioEssays 28: 211,222, 2006. © 2006 Wiley periodicals, Inc. [source] Configuration and timing of Ungava Bay ice streams, Labrador,Ungava, CanadaBOREAS, Issue 1 2003KRISTER N. JANSSON The prominent Ungava Bay landform swarm (UBLS), covering an area of ,260000 km2 south of Ungava Bay, Canada, is defined by drumlins, crag-and-tails, horned crag-and-tails and flutes indicating convergent ice flow towards Ungava Bay. The UBLS has been difficult to interpret in terms of ice-sheet configuration, dynamics and age. Aerial photograph and satellite image interpretations of the Labrador-Ungava region reveal a previously unrecognized level of complexity within the UBLS consisting of several well-defined segments, most interpreted as representing discrete stream-flow events. Each of the segments is characterized by one or more of the criteria (convergent flow patterns at their heads, attenuated till lineations and abrupt lateral margins) previously suggested as diagnostic for formation by fast-flowing ice (ice streams). The UBLS reflects the most direct and probably fastest contact (in terms of sediment transport) between the Laurentide Ice Sheet interior and the ocean. It is therefore a prime candidate for abrupt changes in glacial-age northwest Atlantic seafloor sedimentation. [source] Electrochemical Processing of Carbon DioxideCHEMSUSCHEM CHEMISTRY AND SUSTAINABILITY, ENERGY & MATERIALS, Issue 5 2008Colin Oloman Prof. Abstract With respect to the negative role of carbon dioxide on our climate, it is clear that the time is ripe for the development of processes that convert CO2 into useful products. The electroreduction of CO2 is a prime candidate here, as the reaction at near-ambient conditions can yield organics such as formic acid, methanol, and methane. Recent laboratory work on the 100,A scale has shown that reduction of CO2 to formate (HCO2,) may be carried out in a trickle-bed continuous electrochemical reactor under industrially viable conditions. Presuming the problems of cathode stability and formate crossover can be overcome, this type of reactor is proposed as the basis for a commercial operation. The viability of corresponding processes for electrosynthesis of formate salts and/or formic acid from CO2 is examined here through conceptual flowsheets for two process options, each converting CO2 at the rate of 100,tonnes per day. [source] The heat shock protein 70 molecular chaperone network in the pancreatic endoplasmic reticulum , a quantitative approachFEBS JOURNAL, Issue 19 2007Andreas Weitzmann Traditionally, the canine pancreatic endoplasmic reticulum (ER) has been the workhorse for cell-free studies on protein transport into the mammalian ER. These studies have revealed multiple roles for the major ER-luminal heat shock protein (Hsp) 70, IgG heavy chain-binding protein (BiP), at least one of which also involves the second ER-luminal Hsp70, glucose-regulated protein (Grp) 170. In addition, at least one of these BiP activities depends on Hsp40. Up to now, five Hsp40s and two nucleotide exchange factors, Sil1 and Grp170, have been identified in the ER of different mammalian cell types. Here we quantified the various proteins of this chaperone network in canine pancreatic rough microsomes. We also characterized the various purified proteins with respect to their affinities for BiP and their effect on the ATPase activity of BiP. The results identify Grp170 as the major nucleotide exchange factor for BiP, and the resident ER-membrane proteins ER-resident J-domain protein 1 plus ER-resident J-domain protein 2/Sec63 as prime candidates for cochaperones of BiP in protein transport in the pancreatic ER. Thus, these data represent a comprehensive analysis of the BiP chaperone network that was recently linked to two human inherited diseases, polycystic liver disease and Marinesco,Sjögren syndrome. [source] Two candidate tumor suppressor genes, MEOX2 and SOSTDC1, identified in a 7p21 homozygous deletion region in a Wilms tumorGENES, CHROMOSOMES AND CANCER, Issue 12 2009Junjiro Ohshima A SNP-based array analysis of 100 Wilms tumors (WT) from 97 patients identified 7p alterations (hemizygous and homozygous deletions and uniparental disomy) in nine tumors. The homozygous deletion (HD) region of 7p21 found in one tumor partially overlapped with another HD region reported previously, and was narrowed down to a 2.1-Mb region. Based on an expression analysis of 10 genes located in the HD region in 3 WT lines and previous studies on tumorigenic roles of MEOX2 and SOSTDC1, we further analyzed these two genes. Sequencing showed no mutation in MEOX2, but two missense mutations (L50F and Q129L) in SOSTDC1 in four tumors; L50F in two tumors was of germline origin. Expression levels (0, 1+ and 2+) of MEOX2 were lower in four tumors with 7p alterations than in 18 tumors with no 7p alterations (P = 0.017), and those of SOSTDC1 tended to be lower in five tumors with 7p alterations or SOSTDC1 mutation than in 17 tumors with no 7p alterations or SOSTDC1 mutation (P = 0.056). There were no significant differences in clinical characteristics between nine patients with 7p alterations and 88 patients with no 7p alterations; however, there was a difference in the status of IGF2 (uniparental disomy, loss of imprinting, or retention of imprinting) between the two patient groups (P = 0.028). Losses of MEOX2 and SOSTDC1 may accelerate angiogenesis and augment signals in the Wnt pathway, respectively. Both genes may be prime candidates for 7p tumor suppressor genes, which may have a role in the progression of Wilms tumorigenesis. © 2009 Wiley-Liss, Inc. [source] Sun Protection is Fun!JOURNAL OF SCHOOL HEALTH, Issue 10 2000A Skin Cancer Prevention Program for Preschools ABSTRACT: Children and their caregivers are prime candidates for intervention to curb the rising incidence of skin cancer in the United States. Preschools provide a unique opportunity to influence the sun protection practices of parents and teachers on behalf of young children. Sun Protection is Fun!, a comprehensive skin cancer prevention program developed by The University of Texas M. D. Anderson Cancer Center in collaboration with The University of Texas-Houston Health Science Center School of Public Health, was introduced to preschools in the greater Houston area. The program's intervention methods are grounded in Social Cognitive Theory and emphasize symbolic modeling, vicarious learning, enactive mastery experiences, and persuasion. Program components include a curriculum and teacher's guide, videos, newsletters, handbooks, staff development, group meetings designed to encourage schoolwide changes to support the program, and sunscreen. The intervention map, including objectives for program development, implementation, and evaluation, is discussed. [source] Genome-wide analysis of the general stress response in Bacillus subtilisMOLECULAR MICROBIOLOGY, Issue 4 2001Chester W. Price Bacteria respond to diverse growth-limiting stresses by producing a large set of general stress proteins. In Bacillus subtilis and related Gram-positive pathogens, this response is governed by the ,B transcription factor. To establish the range of cellular functions associated with the general stress response, we compared the transcriptional profiles of wild and mutant strains under conditions that induce ,B activity. Macroarrays representing more than 3900 annotated reading frames of the B. subtilis genome were hybridized to 33P-labelled cDNA populations derived from (i) wild-type and sigB mutant strains that had been subjected to ethanol stress; and (ii) a strain in which ,B expression was controlled by an inducible promoter. On the basis of their significant ,B -dependent expression in three independent experiments, we identified 127 genes as prime candidates for members of the ,B regulon. Of these genes, 30 were known previously or inferred to be ,B dependent by other means. To assist in the analysis of the 97 new genes, we constructed hidden Markov models (HMM) that identified possible ,B recognition sequences preceding 21 of them. To test the HMM and to provide an independent validation of the hybridization experiments, we mapped the ,B -dependent messages for seven representative genes. For all seven, the 5, end of the message lay near typical ,B recognition sequences, and these had been predicted correctly by the HMM for five of the seven examples. Lastly, all 127 gene products were assigned to functional groups by considering their similarity to known proteins. Notably, products with a direct protective function were in the minority. Instead, the general stress response increased relative message levels for known or predicted regulatory proteins, for transporters controlling solute influx and efflux, including potential drug efflux pumps, and for products implicated in carbon metabolism, envelope function and macromolecular turnover. [source] The Challenging Estrogen Receptor-Negative/ Progesterone Receptor-Negative/HER-2-Negative Patient: A Promising Candidate for Epidermal Growth Factor Receptor-Targeted Therapy?THE BREAST JOURNAL, Issue 4 2006Kalliopi P. Siziopikou MD Abstract: While epidermal growth factor receptor (EGFR)-targeted therapy has been very promising in a number of human malignancies, to date these targeted biologic agents have not proven effective in breast cancer. However, the EGFR tyrosinase inhibitors have been used indiscriminately against all types of breast tumors, perhaps missing a subpopulation of patients who may be prime candidates for EGFR-targeted therapy. In this communication we propose that patients with estrogen receptor (ER)-negative/progesterone receptor (PR)-negative/HER-2-negative tumors, which currently present a therapeutic challenge for the oncologist, may be the subgroup of breast cancer patients that might benefit from specific EGFR-targeted therapies., [source] The Einstein-Elko system , Can dark matter drive inflation?ANNALEN DER PHYSIK, Issue 5-6 2007C.G. Böhmer Abstract Recently, a spin one half matter field with mass dimension one was discovered, called Elko spinors. The present work shows how to introduce these fields into a curved spacetime by the standard covariantisation scheme. After formulating the coupled Einstein-Elko field equations, the spacetime is assumed to be homogeneous and isotropic in order to simplify the resulting field equations. Analytical ghost Elko solutions are constructed which have vanishing energy-momentum tensor without and with cosmological constant. The cosmological Elko theory is finally related to the standard scalar field theory with self interaction that gives rise to inflation and it is pointed out that the Elko spinors are not only prime dark matter candidates but also prime candidates for inflation. [source] Synthesis, Structures, and Optical and Electrochemical Properties of BenzoporphycenesCHEMISTRY - A EUROPEAN JOURNAL, Issue 39 2009Daiki Kuzuhara Abstract The first facile syntheses of free-base di- and tetrabenzoporphycenes and their metal complexes are reported, based on retro-Diels,Alder reactions of the corresponding bicyclo[2.2.2]octadiene-fused porphycenes, prepared by McMurray coupling of ,,,,-diformyldipyrrole. The photophysical and electrochemical properties are analyzed based on UV/Vis absorption, magnetic circular dichroism (MCD), and fluorescence emission, lifetime and quantum yield measurements, cyclic and differential pulse voltammetry (CV and DPV) and time-dependent DFT calculations based on B3LYP geometry optimizations. Benzoporphycenes are found to be prime candidates for future use in photodynamic therapy. [source] | ||||||||||||||||