Acute antibody-mediated rejection in pancreas and kidney transplantation

In this thesis, acute rejection after kidney, simultaneous pancreas and kidney (SPKT), and islets of Langerhans transplantation was addressed. The focus is on acute antibody-mediated rejection (AMR) after transplantation and on a potential strategy using cellular immune modulation to prevent acute rejection. First, we retrospectively evaluated the relevance of diffuse C4d-positive peritubular capillary staining in a well-defined kidney transplantation cohort with proven early acute rejections (Chapter 2). Second, the negative impact of AMR on pancreas graft survival was investigated, which proved to be significant (Chapter 3). We subsequently analyzed all SPKT patients at the LUMC with early pancreas graft loss to examine the role of AMR due to presumed thrombosis and/or acute rejection (Chapter 4). In Chapter 5, a clinical update is presented on islets of Langerhans transplantation, focusing on the alternative _-cell replacement therapy that is currently employed in the LUMC (Chapter 5). Furthermore, we reviewed the role of both lymphatic- and blood-vessel vascularization and the role of neuronal reconnection after islet transplantation with data from our own rat islet transplantation models (Chapter 6). Finally, in a rodent allogeneic islet transplantation model, we attempted to induce tolerance by using donor-derived, dexamethasone-pretreated dendritic cells (Chapter 7).Astellas Pharma BV, Novartis Pharma BV, Roche Nederland BV, Novo Nordisk BV, Sakura Finetek Europe BV, de Nederlandse Transplantatie Vereniging, het Diabetes FondsUBL - phd migration 201

Transposable elements maintain genome-wide heterozygosity in inbred populations.

Elevated levels of inbreeding increase the risk of inbreeding depression and extinction, yet many inbred species are widespread, suggesting that inbreeding has little impact on evolutionary potential. Here, we explore the potential for transposable elements (TEs) to maintain genetic variation in functional genomic regions under extreme inbreeding. Capitalizing on the mixed mating system of Arabidopsis lyrata, we assess genome-wide heterozygosity and signatures of selection at single nucleotide polymorphisms near transposable elements across an inbreeding gradient. Under intense inbreeding, we find systematically elevated heterozygosity downstream of several TE superfamilies, associated with signatures of balancing selection. In addition, we demonstrate increased heterozygosity in stress-responsive genes that consistently occur downstream of TEs. We finally reveal that TE superfamilies are associated with specific signatures of selection that are reproducible across independent evolutionary lineages of A. lyrata. Together, our study provides an important hypothesis for the success of self-fertilizing species

On the Connection of Anisotropic Conductivity to Tip Induced Space Charge Layers in Scanning Tunneling Spectroscopy of p-doped GaAs

The electronic properties of shallow acceptors in p-doped GaAs{110} are investigated with scanning tunneling microscopy at low temperature. Shallow acceptors are known to exhibit distinct triangular contrasts in STM images for certain bias voltages. Spatially resolved I(V)-spectroscopy is performed to identify their energetic origin and behavior. A crucial parameter - the STM tip's work function - is determined experimentally. The voltage dependent potential configuration and band bending situation is derived. Ways to validate the calculations with the experiment are discussed. Differential conductivity maps reveal that the triangular contrasts are only observed with a depletion layer present under the STM tip. The tunnel process leading to the anisotropic contrasts calls for electrons to tunnel through vacuum gap and a finite region in the semiconductor.Comment: 11 pages, 8 figure

Light, alertness, and alerting effects of white light:A literature overview

Light is known to elicit non-image-forming responses, such as effects on alertness. This has been reported especially during light exposure at night. Nighttime results might not be translatable to the day. This article aims to provide an overview of (1) neural mechanisms regulating alertness, (2) ways of measuring and quantifying alertness, and (3) the current literature specifically regarding effects of different intensities of white light on various measures and correlates of alertness during the daytime. In general, the present literature provides inconclusive results on alerting effects of the intensity of white light during daytime, particularly for objective measures and correlates of alertness. However, the various research paradigms employed in earlier studies differed substantially, and most studies tested only a limited set of lighting conditions. Therefore, the alerting potential of exposure to more intense white light should be investigated in a systematic, dose-dependent manner with multiple correlates of alertness and within one experimental paradigm over the course of day

Evolutie in actie. Behoud van de zeldzame Duinwespenorchis in de kustduinen-

Ecological speciation is the process by which one species diverges intotwo distinct phylogenetic lineages that gradually become reproductivelyisolated from each other after they have colonized a new habitat. Because ecological speciation typically occurs across a continuum of time and several intermediate stages, often called ecological races or ecotypes, can be discerned during the speciation process, it may result in a complex of taxa among which species limits are difficult to define. A typical example of a species group among which species limits are difficult to define is the genus Epipactis. It contains a complex of autogamous and non-autogamous taxa that may have arisen after the colonization of new habitats, followed by rapid adaptation and evolutionary changes in key traits that allow establishment and survival in these newly colonized habitats. However, the taxonomic status of these species is problematic and different authors have treated the taxonomy of Epipactis in different ways, some recognizing the different taxa as distinct species, others considering them only as minor intraspecific variants or ecological races. Here we present the results of genomic, meta-genomic and morphological analyses aimed at investigating the taxonomic status of coastal dune populations of the widespread terrestrial orchid Epipactis helleborine. Investigations of the mycorrhizal fungi associating with coastal dune populations and typical forest populations has shown that they associate with significantly different fungal communities. Crossing experiments show that both taxa easily cross and produce viable seeds. However, germination of seeds of dune populations in forest habitat andvice versa was always lower than that of seeds of coastal populations indune habitats or of forest populations in forest habitat, leading to strong reproductive isolation as a result of immigrant inviability. Genomic analyses using SNP markers further revealed that coastal dune populations diverged only about 50 generations ago from inland populations, went through a significant bottleneck and were most likely the result of a single colonization event. The sampled dune populations also showed very little genetic differentiation and no apparent spatial genetic structure was observed. Overall these results are consistent with a process of genetic divergence after a single very recent colonization event followed by extensive gene flow among populations. From a taxonomic point of view coastal dune populations of E. helleborine should not be treated as a separate species, but rather as an ecotype

Monitoring birds, reptiles and butterflies in the St Katherine Protectorate, Egypt

Fifty-two bird species were recorded during transect and point count surveys of wadis in the St Katherine Protectorate in the mountainous southern region of the Sinai, Egypt. Two species are new to Egypt: Rock Nuthatch (Sitta neumeyer) and Rock Sparrow (Petronia petronia). There were several other notable species: migrants such as Arabian Warbler (Sylvia leucomelaena) and Upcher’s warbler (Hippolais languida); and residents such as Verreaux’s Eagle (Aquila verreauxi), Hume’s Tawny Owl (Strix butleri) and Striated Scops Owl (Otus brucei).Estimates of bird density and descriptions of each wadi are given. Species diversity of wadis within the Ring dyke geological feature bounding the central mountain plateau was not significantly different from wadis outside. Species composition and numbers of individuals varied according to the distribution of water sources, natural trees and Bedouin gardens especially in fruit. These features appear to be particularly important as staging posts for migrants. Numbers ofsome birds increased around tourist areas. Observations of seven species of reptile and ten species of butterfly including endemics arealso presented. Recorded numbers of all groups depended heavily on the time of day

Interpretatie en discussie

The Unification of the Mediterranean World (400 BC - 400 AD