996 resultados para 459


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The term 'paunch calf syndrome' encompasses the multi-organic lethal developmental dysplasia reported in the Romagnola breed of cattle and is characterised by facial deformities, an enlarged and floating abdomen containing considerable abdominal effusion, and hepatic fibrosis. Paunch calf syndrome is caused by a missense mutation in the KDM2B gene (c.2503G>A) that is thought to lead to an amino acid exchange (p.D835N). In this study, the prevalence of carriers of the mutant KDM2B allele (and thus the frequency of the allele) was assessed in selected subpopulations of Romagnola cattle. The prevalence of carriers within top-ranked Romagnola sires over the years 2007-2012 was 29.3% (allele frequency 14.6%). In young bull calves, 30.9% were carriers with an allele frequency of 15.4%.

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We offer here a multimodal discourse analysis of a range of verbal (writing and speech), nonverbal (movement and gesture) and technological (photography and video) resources used by tourists at the Leaning Tower of Pisa. In doing so, we pin-point the recycling and layering of mediatized representations (e.g. guidebooks and official brochures), mediated actions (e.g. climbing the Tower or posing in front of it), and remediated practices (e.g. posting a YouTube video of oneself climbing the 294 steps to the top of the Tower). Through this kind of empirically-based examination of tourists’ discursive and embodied performances – their ways of talking about and behaving in spaces – we witness how people never simply visit places but are always actively shaping and making these places. The Leaning Tower of Pisa is, therefore, as much an emergent production of the tourist imagination as it is a pre-existing, lop-sided construction of stone.

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This paper analyses local geographical contexts targeted by transnational large-scale land acquisitions (>200 ha per deal) in order to understand how emerging patterns of socio-ecological characteristics can be related to processes of large-scale foreign investment in land. Using a sample of 139 land deals georeferenced with high spatial accuracy, we first analyse their target contexts in terms of land cover, population density, accessibility, and indicators for agricultural potential. Three distinct patterns emerge from the analysis: densely populated and easily accessible croplands (35% of land deals); remote forestlands with lower population densities (34% of land deals); and moderately populated and moderately accessible shrub- or grasslands (26% of land deals). These patterns are consistent with processes described in the relevant case study literature, and they each involve distinct types of stakeholders and associated competition over land. We then repeat the often-cited analysis that postulates a link between land investments and target countries with abundant so-called “idle” or “marginal” lands as measured by yield gap and available suitable but uncultivated land; our methods differ from the earlier approach, however, in that we examine local context (10-km radius) rather than countries as a whole. The results show that earlier findings are disputable in terms of concepts, methods, and contents. Further, we reflect on methodologies for exploring linkages between socioecological patterns and land investment processes. Improving and enhancing large datasets of georeferenced land deals is an important next step; at the same time, careful choice of the spatial scale of analysis is crucial for ensuring compatibility between the spatial accuracy of land deal locations and the resolution of available geospatial data layers. Finally, we argue that new approaches and methods must be developed to empirically link socio-ecological patterns in target contexts to key determinants of land investment processes. This would help to improve the validity and the reach of our findings as an input for evidence-informed policy debates.

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(31)P MRS magnetization transfer ((31)P-MT) experiments allow the estimation of exchange rates of biochemical reactions, such as the creatine kinase equilibrium and adenosine triphosphate (ATP) synthesis. Although various (31)P-MT methods have been successfully used on isolated organs or animals, their application on humans in clinical scanners poses specific challenges. This study compared two major (31)P-MT methods on a clinical MR system using heteronuclear surface coils. Although saturation transfer (ST) is the most commonly used (31)P-MT method, sequences such as inversion transfer (IT) with short pulses might be better suited for the specific hardware and software limitations of a clinical scanner. In addition, small NMR-undetectable metabolite pools can transfer MT to NMR-visible pools during long saturation pulses, which is prevented with short pulses. (31)P-MT sequences were adapted for limited pulse length, for heteronuclear transmit-receive surface coils with inhomogeneous B1 , for the need for volume selection and for the inherently low signal-to-noise ratio (SNR) on a clinical 3-T MR system. The ST and IT sequences were applied to skeletal muscle and liver in 10 healthy volunteers. Monte-Carlo simulations were used to evaluate the behavior of the IT measurements with increasing imperfections. In skeletal muscle of the thigh, ATP synthesis resulted in forward reaction constants (k) of 0.074 ± 0.022 s(-1) (ST) and 0.137 ± 0.042 s(-1) (IT), whereas the creatine kinase reaction yielded 0.459 ± 0.089 s(-1) (IT). In the liver, ATP synthesis resulted in k = 0.267 ± 0.106 s(-1) (ST), whereas the IT experiment yielded no consistent results. ST results were close to literature values; however, the IT results were either much larger than the corresponding ST values and/or were widely scattered. To summarize, ST and IT experiments can both be implemented on a clinical body scanner with heteronuclear transmit-receive surface coils; however, ST results are much more robust against experimental imperfections than the current implementation of IT.

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valois (vls) was identified as a posterior group gene in the initial screens for Drosophila maternal-effect lethal mutations. Despite its early genetic identification, it has not been characterized at the molecular level until now. We show that vls encodes a divergent WD domain protein and that the three available EMS-induced point mutations cause premature stop codons in the vls ORF. We have generated a null allele that has a stronger phenotype than the EMS mutants. The vlsnull mutant shows that vls+ is required for high levels of Oskar protein to accumulate during oogenesis, for normal posterior localization of Oskar in later stages of oogenesis and for posterior localization of the Vasa protein during the entire process of pole plasm assembly. There is no evidence for vls being dependent on an upstream factor of the posterior pathway, suggesting that Valois protein (Vls) instead acts as a co-factor in the process. Based on the structure of Vls, the function of similar proteins in different systems and our phenotypic analysis, it seems likely that vls may promote posterior patterning by facilitating interactions between different molecules.

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Egon Caesar Conte Corti

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GABAA receptors are the major inhibitory neurotransmitter receptors in the brain and are the target for many clinically important drugs such as the benzodiazepines. Benzodiazepines act at the high-affinity binding site at the α+/γ- subunit interface. Previously, an additional low affinity binding site for diazepam located in the transmembrane (TM) domain has been described. The compound SJM-3 was recently identified in a prospective screening of ligands for the benzodiazepine binding site and investigated for its site of action. We determined the binding properties of SJM-3 at GABAA receptors recombinantly expressed in HEK-cells using radioactive ligand binding assays. Impact on function was assessed in Xenopus laevis oocytes with electrophysiological experiments using the two-electrode voltage clamp method. SJM-3 was shown to act as an antagonist at the α+/γ- site. At the same time it strongly potentiated GABA currents via the binding site for diazepam in the transmembrane domain. Mutation of a residue in M2 of the α subunit strongly reduced receptor modulation by SJM-3 and a homologous mutation in the β subunit abolished potentiation. SJM-3 acts as a more efficient modulator than diazepam at the site in the trans-membrane domain. In contrast to low concentrations of benzodiazepines, SJM-3 modulates both synaptic and extrasynaptic receptors. A detailed exploration of the membrane site may provide the basis for the design and identification of subtype-selective modulatory drugs.

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In Pierre Robin sequence, a retracted tongue due to micrognathia is thought to physically obstruct palatal shelf elevation and thereby cause cleft palate. However, micrognathia is not always associated with palatal clefting. Here, by using the Bmp7-null mouse model presenting with cleft palate and severe micrognathia, we provide the first causative mechanism linking the two. In wild-type embryos, the genioglossus muscle, which mediates tongue protrusion, originates from the rostral process of Meckel's cartilage and later from the mandibular symphysis, with 2 tendons positive for Scleraxis messenger RNA. In E13.5 Bmp7-null embryos, a rostral process failed to form, and a mandibular symphysis was absent at E17.5. Consequently, the genioglossus muscle fibers were diverted toward the lingual surface of Meckel's cartilage and mandibles, where they attached in an aponeurosis that ectopically expressed Scleraxis. The deflection of genioglossus fibers from the anterior-posterior toward the medial-lateral axis alters their direction of contraction and necessarily compromises tongue protrusion. Since this muscle abnormality precedes palatal shelf elevation, it is likely to contribute to clefting. In contrast, embryos with a cranial mesenchyme-specific deletion of Bmp7 (Bmp7:Wnt1-Cre) exhibited some degree of micrognathia but no cleft palate. In these embryos, a rostral process was present, indicating that mesenchyme-derived Bmp7 is dispensable for its formation. Moreover, the genioglossus appeared normal in Bmp7:Wnt1-Cre embryos, further supporting a role of aberrant tongue muscle attachment in palatal clefting. We thus propose that in Pierre Robin sequence, palatal shelf elevation is not impaired simply by physical obstruction by the tongue but by a specific developmental defect that leads to functional changes in tongue movements.

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Structural composite lumber (SCL) products often possess significantly higher design values than the top grades of solid lumber, making it a popular choice for both residential and commercial applications. The enhanced mechanical properties of SCL are mainly due to defect randomization and densification of the wood fiber, both largely functions of the size, shape and composition (species) of the wood element. Traditionally, SCL manufacturers have used thin, rectangular elements produced from either moderate density softwoods or low density hardwoods. Higher density hardwood species have been avoided, as they require higher pressures to adequately densify and consolidate the wood furnish. These higher pressures can lead to increased manufacturing costs, damage to the wood fiber and/or a product that is too dense, making it heavy and unreceptive to common mechanical fastening techniques. In the northeastern United States high density, diffuse-porous hardwoods (such as maple, beech and birch) are abundant. Use of these species as primary furnish for a SCL product may allow for a competitive advantage in terms of resource cost against products that rely on veneer grade logs. Proximity to this abundant and relatively inexpensive resource may facilitate entry of SCL production facilities in the northeastern United States, where currently none exist. However, modifications to current strand sizes, geometries or production techniques will likely be required to allow for use of these species. A new SCL product concept has been invented allowing for use of these high density hardwoods. The product, referred to as long-strand structural composite lumber (LSSCL), uses strands of significantly larger cross sectional areas and volumes than existing SCL products. In spite of the large strand size, satisfactory consolidation is achieved without excessive densification of the wood fiber through use of a symmetrical strand geometric cross-section. LSSCL density is similar to that of existing SCL products, but is due mainly to the inherent density of the species, rather than through densification. An experiment was designed and conducted producing LSSCL from both large (7/16”) and small (1/4”) strands, of both square and triangular geometric cross sections. Testing results indicate that the large, triangular strands produce LSSCL beams with projected design values of: Modulus of elasticity (MOEapp) – 1,750,000 psi; Allowable bending stress (Fb) – 2750 psi; Allowable shear stress (Fv) – 260 psi. Several modifications are recommended which may lead to improvement of these values, likely allowing for competition against existing SCL products.

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Neural tube defects (NTDs) are the most common severely disabling birth defects in the United States, with a frequency of approximately 1–2 of every 1,000 births. This text includes the identification and evaluation of candidate susceptibility genes that confer risk for the development of neural tube defects (NTDs). The project focused on isolated meningomyelocele, also termed spina bifida (SB). ^ Spina bifida is a complex disease with multifactorial inheritance, therefore the subject population (consisting of North American Caucasians and Hispanics of Mexicali-American descent) was composed of 459 simplex SB families who were tested for genetic associations utilizing the transmission disequilibrium test (TDT), a nonparametric linkage technique. Three categories of candidate genes were studied, including (1) human equivalents of genes determined in mouse models to cause NTDs, (2) HOX and PAX genes, and (3) the MTHFR gene involved in the metabolic pathway of folate. ^ The C677T variant of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene was the first mutation in this gene to be implicated as a risk factor for NTDs. Our evaluation of the MTHFR gene provides evidence that maternal C677T homozygosity is a risk factor for upper level spina bifida defects in Hispanics [OR = 2.3, P = 0.02]. This observed risk factor is of great importance due to the high prevalence of this homozygous genotype in the Hispanic population. Additionally, maternal C677T/A1298C compound heterozygosity is a risk factor for upper level spina bifida defects in non-Hispanic whites [OR = 3.6, P = 0.03]. ^ For TDT analysis, our total population of 1128 subjects were genotyped for 54 markers from within and/or flanking the 20 candidate genes/gene regions of interest. Significant TDT findings were obtained for 3 of the 54 analyzed markers: d20s101 flanking the PAX1 gene (P = 0.019), d1s228 within the PAX7 gene (P = 0.011), and d2s110 within the PAX8 gene (P = 0.013). These results were followed-up by testing the genes directly for mutations utilizing single-strand conformational analysis (SSCA) and direct sequencing. Multiple variations were detected in each of these PAX genes; however, these variations were not passed from parent to child in phase with the positively transmitted alleles. Therefore, these variations do not contribute to the susceptibility of spina bifida, but rather are previously unreported single nucleotide polymorphisms. ^

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veröffentlicht in: Arthur Hübscher (Hrsg), Arthur Schopenhauer Gesammelte Briefe, Bonn 1978, Nr. 459