Position of chromosomes 18, 19, 21 and 22 in 3D-preserved interphase nuclei of human and gorilla and white hand gibbon

<p>Abstract</p> <p>Background</p> <p>Even though comparative nuclear architecture studies in hominoids are sparse, nuclear chromosome architecture was shown to be conserved during hominoid evolution. Thus, it is suspected that yet unknown biological mechanisms must underlie this observation.</p> <p>Results</p> <p>Here for the first time a combination of multicolor banding (MCB) and three-dimensional analysis of interphase cells was used to characterize the position and orientation of human chromosomes #18, #19, #21 and #22 and their homologues in primate B-lymphocytic cells. In general, our data is in concordance with previous studies. The position of the four studied human chromosomes and their homologues were conserved during primate evolution. However, comparison of interphase architecture in human B-lymphocytic cells and sperm revealed differences of localization of acrocentric chromosomes. The latter might be related to the fact that the nucleolus organizing region is not active in sperm.</p> <p>Conclusion</p> <p>Studies in different tissue types may characterize more – potentially biologically relevant differences in nuclear architecture.</p

Chromosome distribution in human sperm – a 3D multicolor banding-study

<p>Abstract</p> <p>Background</p> <p>Nuclear architecture studies in human sperm are sparse. By now performed ones were practically all done on flattened nuclei. Thus, studies close at the <it>in vivo </it>state of sperm, i.e. on three-dimensionally conserved interphase cells, are lacking by now. Only the position of 14 chromosomes in human sperm was studied.</p> <p>Results</p> <p>Here for the first time a combination of multicolor banding (MCB) and three-dimensional analysis of interphase cells was used to characterize the position and orientation of all human chromosomes in sperm cells of a healthy donor. The interphase nuclei of human sperm are organized in a non-random way, driven by the gene density and chromosome size.</p> <p>Conclusion</p> <p>Here we present the first comprehensive results on the nuclear architecture of normal human sperm. Future studies in this tissue type, e.g. also in male patients with unexplained fertility problems, may characterize yet unknown mechanisms of infertility.</p

Ion Energy Measurements in Plasma Immersion Ion Implantation

This thesis investigates ion energy distributions (IEDs) during plasma immersion ion implantation (PIII). PIII is a surface modification technique where an object is placed in a plasma and pulse biased with large negative voltages. The energy distribution of implanted ions is important in determining the extent of surface modifications. IED measurements were made during PIII using a pulse biased retarding field energy analyser (RFEA) in a capacitive RF plasma. Experimental results were compared with those obtained from a two dimensional numerical simulation to help explain the origins of features in the IEDs. Time resolved IED measurements were made during PIII of metal and insulator materials and investigated the effects of the use of a metal mesh over the surface and the effects of insulator surface charging. When the pulse was applied to the RFEA, the ion flux rapidly increased above the pulse-off value and then slowly decreased during the pulse. The ion density during the pulse decreased below values measured when no pulse was applied to the RFEA. This indicates that the depletion of ions by the pulsed RFEA is greater than the generation of ions in the plasma. IEDs measured during pulse biasing showed a peak close to the maximum sheath potential energy and a spread of ions with energies between zero and the maximum ion energy. Simulations showed that the peak is produced by ions from the sheath edge directly above the RFEA inlet and that the spread of ions is produced by ions which collide in the sheath and/or arrive at the RFEA with trajectories not perpendicular to the RFEA front surface. The RFEA discriminates ions based only on the component of their velocity perpendicular to the RFEA front surface. To minimise the effects of surface charging during PIII of an insulator, a metal mesh can be placed over the insulator and pulse biased together with the object. Measurements were made with metal mesh cylinders fixed to the metal RFEA front surface. The use of a mesh gave a larger ion flux compared to the use of no mesh. The larger ion flux is attributed to the larger plasma-sheath surface area around the mesh. The measured IEDs showed a low, medium and high energy peak. Simulation results show that the high energy peak is produced by ions from the sheath above the mesh top. The low energy peak is produced by ions trapped by the space charge potential hump which forms inside the mesh. The medium energy peak is produced by ions from the sheath above the mesh corners. Simulations showed that the IED is dependent on measurement position under the mesh. To investigate the effects of insulator surface charging during PIII, IED measurements were made through an orifice cut into a Mylar insulator on the RFEA front surface. With no mesh, during the pulse, an increasing number of lower energy ions were measured. Simulation results show that this is due to the increase in the curvature of the sheath over the orifice region as the insulator potential increases due to surface charging. The surface charging observed at the insulator would reduce the average energy of ions implanted into the insulator during the pulse. Compared to the case with no mesh, the use of a mesh increases the total ion flux and the ion flux during the early stages of the pulse but does not eliminate surface charging. During the pulse, compared to the no mesh case, a larger number of lower energy ions are measured. Simulation results show that this is caused by the potential in the mesh region which affects the trajectories of ions from the sheaths above the mesh top and corners and results in more ions being measured with trajectories less than ninety degrees to the RFEA front surface

In Vivo Emergence of UL56 C325Y Cytomegalovirus Resistance to Letermovir in a Patient with Acute Myeloid Leukemia after Hematopoietic Cell Transplantation

CMV associated tissue-invasive disease is associated with a considerable risk of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Recently, the terminase inhibitor letermovir (LMV) has been approved for prophylaxis of CMV infection in HSCT. We hereby report a 60-year-old female experiencing CMV reactivation after HSCT in a CMV seronegative donor-constellation. Due to ongoing elevated CMV viral load and drug-associated myelosuppression, which prevented ganciclovir therapy, treatment was replaced by foscarnet. Due to nephrotoxicity, foscarnet was switched to LMV. The patient developed skin GvHD and prednisolone was started. Subsequently, CMV viremia worsened despite LMV therapy. Genotyping revealed the mutation C325Y of the CMV UL56 terminase being associated with high-level resistance against LMV. Prolonged uncontrolled low-level viremia due to prednisolone treatment may have favored the selection of drug-resistant CMV. Despite the excellent toxicity profile of LMV, physicians should be aware of risk factors for the emergence of resistance

A Mosquito Bite with Devastating Complications in an Immunocompromised Patient

Infectious complications such as invasive aspergillosis or infection with Stenotrophomonas maltophilia (SM) in immunocompromised patients are associated with a high mortality rate. Our report concerns a 40-year-old male newly diagnosed very severe aplastic anemia (vSAA) who in consequence of a mosquito bite was suffering from skin lesion and consecutive soft tissue phlegmon subsequent to the administration of antithymocyte globulin; a full-thickness autologous meshed skin graft successfully performed to cover skin ulcera after allogeneic stem cell transplantation (SCT). This unusual case illustrates the importance of appropriate diagnosis, anti-infective therapy and close interdisciplinary diagnostic algorithms to minimalize side effects and the selection of resistant strains and to improve patients’ outcome