What Can We Learn from FGF-2 Isoform-Specific Mouse Mutants? Differential Insights into FGF-2 Physiology In Vivo

Fibroblast growth factor 2 (FGF-2), ubiquitously expressed in humans and mice, is functionally involved in cell growth, migration and maturation in vitro and in vivo. Based on the same mRNA, an 18-kilo Dalton (kDa) FGF-2 isoform named FGF-2 low molecular weight (FGF-2LMW) isoform is translated in humans and rodents. Additionally, two larger isoforms weighing 21 and 22 kDa also exist, summarized as the FGF-2 high molecular weight (FGF-2HMW) isoform. Meanwhile, the human FGF-2HMW comprises a 22, 23, 24 and 34 kDa protein. Independent studies verified a specific intracellular localization, mode of action and tissue-specific spatiotemporal expression of the FGF-2 isoforms, increasing the complexity of their physiological and pathophysiological roles. In order to analyze their spectrum of effects, FGF-2LMW knock out (ko) and FGF-2HMWko mice have been generated, as well as mice specifically overexpressing either FGF-2LMW or FGF-2HMW. So far, the development and functionality of the cardiovascular system, bone formation and regeneration as well as their impact on the central nervous system including disease models of neurodegeneration, have been examined. This review provides a summary of the studies characterizing the in vivo effects modulated by the FGF-2 isoforms and, thus, offers a comprehensive overview of its actions in the aforementioned organ systems.     

Comparison of the GFFF and LALLS Methods for the Measurement of Starch Granule Size Distribution in Spring Barley Caryopses

A newly developed method GFFF (Gravitational Field‐Flow Fractionation) and the well known method LALLS (Low Angle Laser Light Scattering) were used to assess starch granule size distribution of ten varieties of spring barley. As a distribution criterion, the ratio of starch granule content larger than 8 μm (type A) and smaller than 8 μm (type B) was chosen. Both methods divided the observed set in a similar way. Varieties Akcent, Forum and Atribut formed a variety set with the highest ratio of large and small starch granules. Varieties Scarlet and Kompakt had intermediate ratios. The remaining five varieties Amulet, Novum, Olbram, Tolar and Krona had the lowest ratios of large and small starch granules. Statistical analysis showed that there was a highly significant correlation between the GFFF and LALLS methods.     

Modellqualität als Indikator für Softwarequalität: eine Taxonomie

Zusammenfassung  Komplexit?t, Anforderungsmanagement und Variantenvielfalt sind zentrale Herausforderungen bei der Entwicklung und Evolution heutiger softwaregesteuerter Systeme. Diesen wird zunehmend durch den Einsatz modellbasierter Entwicklungsmethoden begegnet. Dadurch wird das Modell zum zentralen Artefakt und die Erstellung und Nutzung von Modellen zu einer zentralen T?tigkeit in der Softwareentwicklung. Mit der Bedeutung der Modelle steigen auch die Ansprüche an ihre Qualit?t. Dieser Beitrag untersucht die Implikationen, die daraus entstehen, insbesondere werden sinnvolle Qualit?tsmerkmale für softwarebeschreibende Modelle identifiziert und diskutiert.     

Structural determination of N-2''-hydroxyoctadecenoyl-1-O-beta-D-glucopyranosyl-9-methyl-4, 8-sphingadienine from species of Aspergillus

The barrier function, surface biochemistry, and morphology of confluent monolayers of endothelial cells isolated from different segments of the bovine lung vasculature [microvessels (BLMVEC), vein (BPVEC) and artery (BPAEC)] were grown in culture and compared. A number of common cell surface proteins were identified along with two proteins of 46 and 48 kDa found exclusively on BPVEC. Lectin affinity chromatography revealed multiple glycosylation differences. The lectins, Arachis hypogaea (AHA) and Lycopersicum esculentum (LEA) agglutinins, interacted with several glycoproteins of BLMVEC but not of BPAEC. Bandeiraea simplicifolia (BS-1) and Caragana arborescens (CAA) agglutinins recognized several glycoproteins of BPVEC and BPAEC but not BLMVEC. Permeabilities were much lower for BLMVEC than BPAEC or BPVEC monolayers, with a range of about 16-fold less for sucrose to 2-fold less for albumin. Electron microscopy revealed that BLMVEC have a greater surface density of plasmalemmal vesicles (approximately 4-fold) and more extensively developed intercellular junctions with more focal membrane adhesion sites per junction (approximately 9-fold) than the other cells. We conclude that: i) BLMVEC monolayers form a much more restrictive barrier to molecular transport as a result of the tighter junctional formation; and ii) endothelial surface glycoproteins may be differentially glycosylated depending on their segmental location within the vasculature.     

The anti-tumor arotinoid Ro 40-8757 protects bone marrow from the toxic effects of 5-fluorouracil

We have previously shown that strychnine mimics the cytoprotective properties of glycine in renal proximal tubule (RPT) suspensions exposed to antimycin A (AA). The aims of this study were to determine whether the cytoprotective properties of strychnine applied to various types of nephrotoxicants and to examine the temporal aspects of the cytoprotection of glycine and strychnine. Tubular release of LDH activity was used as a marker of cell death. Glycine (2 mM) or strychnine (1 mM) added 5 min prior to the toxicant decreased LDH release in rabbit RPT suspensions exposed to 25 microM tetrafluoroethyl-L-cysteine (TFEC), 10 microM HgCl2, 0.5 mM t-butyl hydroperoxide (TBHP), or 0.2 mM bromohydroquinone (BHQ) for 4 hr, or 2 mM sodium cyanide (NaCN) for 2 hr. The relative rank order of effectiveness of glycine and strychnine was NaCN = TFEC > BHQ > DCVC > TBHP > HgCl2. The temporal aspects of strychnine and glycine protection were examined by exposing RPT to either AA or TFEC for 1 or 3 hr, respectively, and then adding either 1 mM glycine or 1 mM strychnine. Glycine and strychnine decreased LDH release in AA-treated RPT at 1.25 and 2 hr and TFEC-treated RPT at 4 hr. In addition, when RPT exposed to AA or TFEC and treated with strychnine or glycine were washed at either 1 or 4 hr, protection was eliminated at later time points. When glycine was added to RPT treated with either PCBC, TFEC, or DCVC 5 min prior to or 30, 60, 120, and 180 min following toxicant addition, LDH release was reduced at all time points. These results demonstrate that strychnine and glycine protect RPT from a variety of diverse nephrotoxicants, strychnine and glycine do not need to be present at the time of toxic insult, strychnine and glycine cytoprotection is reversible, and strychnine and glycine act in the late phase of necrotic cell injury.     

Sound localization in the median sagittal plane by listeners with presbyacusis

In Experiment 1, a group of listeners with substantial hearing loss due to presbyacusis and a group of listeners with normal hearing were given three localization tests: a frontal plane test in which they judged whether sounds came from the left, overhead, or the right; a sagittal plane test in which they judged whether sounds came from directly in front, overhead, or behind; and an elevation test in which they judged the vertical position of sounds coming from in front. The two groups performed similarly on the frontal plane test, which chiefly depended upon their ability to use binaural localization cues. They performed differently on the sagittal plane and elevation tests, for which the predominant localization cues were spectral. The listeners with presbyacusis were substantially less accurate than those with normal hearing in both of these instances. They had particular difficulty judging source elevation, rarely scoring much above chance. Follow-up testing of a group of subjects in the early stages of presbyacusis showed localization performance that was intermediate to the other two groups, but far more like that of the normal-hearing listeners. In Experiment 2, additional tests were run with the following conditions designed to encourage improved performance by listeners with presbyacusic hearing loss: (1) filtering of stimuli to preclude masking of more informative high-frequency components by low frequencies; (2) simplification of the elevation test and greater spatial separation of its loudspeaker sources; and (3) use of hearing aids. Conditions 1 and 2 had no appreciable effect on performance; condition 3 significantly improved presbyacusic listeners' ability to localize in the sagittal plane, particularly when sounds came from the front.