Eine Lagerstätte kreidezeitlicher und paläogener Chondrichthyes-Reste bei Fürstenau (Niedersachsen)

Aus einer durch Glaziotektonik verstellten Kiesbank innerhalb einer Folge mariner Sedimente bei Fürstenau wird eine 49 Arten umfassende Liste von Chondrichthyes genannt. Diese Fauna enthält Arten des Campans, Oberpaläozäns und Unter- bis Mitteleozäns. Die Entstehung dieser Kiesbank könnte einerseits einer Transgressionsphase oder andererseits einer Kondensation verbunden mit der Erosion von Folgen des oben genannten Alters während des Lediums zugeschrieben werden. Diese Kiesbank besitzt in Oldenburg und im Emsland eine weite Verbreitung

Fluorescence Spectroscopy of Recoverin Function and Conformation

Recoverin is a neuronal calcium sensor protein (NCS protein) from the vertebrate photoreceptor which is involved in light adaptation. Recoverin changes its conformation upon sequential binding of two calcium ions. This conformational change induces the extrusion of a covalently attached myristoyl residue from a hydrophobic binding pocket which enables Recoverin to interact with lipid membranes (calcium myristoyl switch). In this thesis, I report on my investigation of Recoverin�s calcium myristoyl switch, using a recently developed modification of fluorescence correlation spectroscopy (FCS) that is called dual focus FCS (2fFCS). This method allows for measuring absolute diffusion coefficients with an accuracy of better than a few percent. Recoverin, and the Recoverin mutants E85Q and E121Q which bind only one or no Ca2+, respectively, were labeled with the fluorescent dye Alexa647. Differences in the hydrodynamic radius due to conformational changes of Recoverin and its mutants upon calcium binding were monitored by measuring the diffusion coefficient of these molecules as a function of free calcium concentration. The calcium dependent interaction of Recoverin with lipid membranes was measured in solutions of small unilamellar vesicles (SUVs) of different lipid composition. Again, diffusion measurements were used to determine the fraction of free and lipid bound Recoverin using the strongly different diffusion coefficients of both fractions. To account for the fluorescence brightness difference of the dye label when in solution and close to a lipid membrane, a new three photon correlation analysis was developed and tested

UPPER OLIGOCENE BRACHIOPODS FROM NW GERMANY, WITH DESCRIPTION OF A NEW PLATIDIINAE GENUS, GERMANOPLATIDIA N. GEN.

Upper Oligocene brachiopods of NW Germany were studied in two collections: the Naturalis Biodiversity Center (Leiden, the Netherlands) and the F. von der Hocht private Collection (Kerpen, Germany). Overall, six brachiopod taxa have been identified. Generic attributions of “Rhynchonella” supraoligocaenica Görges, 1952 (Aphelesia) and “Terebratula” pusilla Philippi, 1843 (Germanoplatidia n. gen) have been solved. The Chattian occurrence of Aphelesia is the first confirmed record of the genus in the Paleogene. Chattian record of the well-known Neogene Discinisca fallens (Wood, 1872) confirms that faunal change within brachiopods happened before the Paleogene/Neogene boundary. Similarly to the Mediterranean Terebratula-Aphelesia association, Aphelesia occurs also together with a large terebratulide genus (Pliothyrina) in the upper Oligocene Pre-North Sea. Along with some previously recognized genera (Orthothyris, Bronnothyris, Rugia), a further brachiopod evolutionary lineage was found to survive from the Mesozoic to the Paleogene (Aemula-Germanoplatidia n. gen.). According to the morphological characters of the genus and sedimentological characters of the surrounding deposits, Germanoplatidia n. gen. species lived on sandy bottom environments, and attached to small hard objects in the fine sediment by a pedicle longer than that of Aemula. Half of the identified species are endemic in Pre-North Sea. Here we document the first record of Argyrotheca bitnerae Dulai in Dulai & Stachacz, 2011 from the Pre-North Sea; this recently described species shows a cosmopolitan distribution in the Cenozoic. &nbsp

Surface sticking and lateral diffusion of lipids in supported bilayers

The diffusion of fluorescently labeled lipids in supported bilayers is studied using two different methods: Z-scan fluorescence correlation spectroscopy (z-scan FCS) and two-focus fluorescence correlation spectroscopy (2f-FCS). It is found that the data can be fitted consistently only when taking into account partial sticking of the labeled lipids to the supporting glass surface. A kinetic reaction-diffusion model is developed and applied to the data. We find a very slow sticking rate which, however, when neglected, leads to strongly varying estimates of the free diffusion coefficient. The study reveals a strong sensitivity of FCS on even slight binding/unbinding kinetics of the labeled molecules, which has significance for related diffusion measurements in cellular lipid membranes

The common reflecting element (CRE) method revisited

The common reflecting element (CRE) method is an interesting alternative to the familiar methods of common midpoint (CMP) stack or migration to zero offset (MZO). Like these two methods, the CRE method aims at constructing a stacked zero-offset section from a set of constant-offset sections. However, it requires no more knowledge about the generally laterally inhomogeneous subsurface model than the near-surface values of the velocity field. In addition to being a tool to construct a stacked zero-offset section, the CRE method simultaneously obtains information about the laterally inhomogeneous macrovelocity model. An important feature of the CRE method is that it does not suffer from pulse stretch. Moreover, it gives an alternative solution for conflicting dip problems. In the 1-D case, CRE is closely related to the optical stack. For the price of having to search for two data-derived parameters instead of one, the CRE method provides important advantages over the conventional CMP stack. Its results are similar to those of the MZO process, which is commonly implemented as an NMO correction followed by a dip moveout (DMO) correction applied to the original constant-offset section. The CRE method is based on 2-D kinematic considerations only and is not an amplitude-preserving process.65397999

(R)-[11C]Verapamil PET studies to assess changes in P-glycoprotein expression and functionality in rat blood-brain barrier after exposure to kainate-induced status epilepticus

<p>Abstract</p> <p>Background</p> <p>Increased functionality of efflux transporters at the blood-brain barrier may contribute to decreased drug concentrations at the target site in CNS diseases like epilepsy. In the rat, pharmacoresistant epilepsy can be mimicked by inducing status epilepticus by intraperitoneal injection of kainate, which leads to development of spontaneous seizures after 3 weeks to 3 months. The aim of this study was to investigate potential changes in P-glycoprotein (P-gp) expression and functionality at an early stage after induction of status epilepticus by kainate.</p> <p>Methods</p> <p><it>(R)</it>-[¹¹C]verapamil, which is currently the most frequently used positron emission tomography (PET) ligand for determining P-gp functionality at the blood-brain barrier, was used in kainate and saline (control) treated rats, at 7 days after treatment. To investigate the effect of P-gp on <it>(R)</it>-[¹¹C]verapamil brain distribution, both groups were studied without or with co-administration of the P-gp inhibitor tariquidar. P-gp expression was determined using immunohistochemistry in post mortem brains. <it>(R)</it>-[¹¹C]verapamil kinetics were analyzed with approaches common in PET research (Logan analysis, and compartmental modelling of individual profiles) as well as by population mixed effects modelling (NONMEM).</p> <p>Results</p> <p>All data analysis approaches indicated only modest differences in brain distribution of <it>(R)</it>-[¹¹C]verapamil between saline and kainate treated rats, while tariquidar treatment in both groups resulted in a more than 10-fold increase. NONMEM provided most precise parameter estimates. P-gp expression was found to be similar for kainate and saline treated rats.</p> <p>Conclusions</p> <p>P-gp expression and functionality does not seem to change at early stage after induction of anticipated pharmacoresistant epilepsy by kainate.</p

3D MRI-based tumor delineation of ocular melanoma and its comparison with conventional techniques

The aim of this study is to (1) compare the delineation of the tumor volume for ocular melanoma on high-resolution three-dimensional (3D) T2-weighted fast spin echo magnetic resonance imaging (MRI) images with conventional techniques of A- and B-scan ultrasound, transcleral illumination, and placement of tantalum markers around tumor base and (2) to evaluate whether the surgically placed marker ring tumor delineation can be replaced by 3D MRI based tumor delineation. High-resolution 3D T2-weighted fast spin echo (3D FSE) MRI scans were obtained for 60 consecutive ocular melanoma patients using a 1.5 T MRI (GE Medical Systems, Milwaukee, WI), in a standard head coil. These patients were subsequently treated with proton beam therapy at the UC Davis Cyclotron, Davis, CA. The tumor was delineated by placement of tantalum rings (radio-opaque markers) around the tumor periphery as defined by pupillary transillumination during surgery. A point light source, placed against the sclera, was also used to confirm ring agreement with indirect ophthalmoscopy. When necessary, intraoperative ultrasound was also performed. The patients were planned using EYEPLAN software and the tumor volumes were obtained. For analysis, the tumors were divided into four categories based on tumor height and basal diameter. In order to assess the impact of high-resolution 3D T2 FSE MRI, the tumor volumes were outlined on the MRI scans by two independent observers and the tumor volumes calculated for each patient. Six (10%) of 60 patients had tumors, which were not visible on 3D MRI images. These six patients had tumors with tumor heights &lt;= 3 mm. A small intraobserver variation with a mean of (-0.22 +/- 4)% was seen in tumor volumes delineated by 3D T2 FSE MR images. The ratio of tumor volumes measured on MRI to EYEPLAN for the largest to the smallest tumor volumes varied between 0.993 and 1.02 for 54 patients. The tumor volumes measured directly on 3D T2 FSE MRI ranged from 4.03 to 0.075 cm(3). with a mean of 0.87 +/- 0.84 cm3. The tumor shapes obtained from 3D T2 FSE MR images were comparable to the tumor shapes obtained using EYEPLAN software. The demonstration of intraocular tumor volumes with the high-resolution 3D fast spin echo T2 weighted MRI is excellent and provides additional information on tumor shape. We found a high degree of accuracy for tumor volumes with direct MRI volumetric measurements in uveal melanoma patients. In some patients with extra large tumors, the tumor base and shape was modified, because of the additional information obtained from 3D T2 FSE MR images. (c) 2005 American Association of Physicists in Medicine

Cerebral microdialysis in clinical studies of drugs: pharmacokinetic applications

The ability to deliver drug molecules effectively across the blood–brain barrier into the brain is important in the development of central nervous system (CNS) therapies. Cerebral microdialysis is the only existing technique for sampling molecules from the brain extracellular fluid (ECF; also termed interstitial fluid), the compartment to which the astrocytes and neurones are directly exposed. Plasma levels of drugs are often poor predictors of CNS activity. While cerebrospinal fluid (CSF) levels of drugs are often used as evidence of delivery of drug to brain, the CSF is a different compartment to the ECF. The continuous nature of microdialysis sampling of the ECF is ideal for pharmacokinetic (PK) studies, and can give valuable PK information of variations with time in drug concentrations of brain ECF versus plasma. The microdialysis technique needs careful calibration for relative recovery (extraction efficiency) of the drug if absolute quantification is required. Besides the drug, other molecules can be analysed in the microdialysates for information on downstream targets and/or energy metabolism in the brain. Cerebral microdialysis is an invasive technique, so is only useable in patients requiring neurocritical care, neurosurgery or brain biopsy. Application of results to wider patient populations, and to those with different pathologies or degrees of pathology, obviously demands caution. Nevertheless, microdialysis data can provide valuable guidelines for designing CNS therapies, and play an important role in small phase II clinical trials. In this review, we focus on the role of cerebral microdialysis in recent clinical studies of antimicrobial agents, drugs for tumour therapy, neuroprotective agents and anticonvulsants