The respiratory tract is particularly vulnerable to infections from various pathogens, often leading to severe illnesses. Co-infections involving multiple pathogens are commonly observed in respiratory diseases, although their underlying mechanisms remain poorly understood. Lung epithelial cells play a crucial role in the body’s defense and are primary targets for many pathogens, which exploit them for attachment and entry. This study investigates the molecular mechanism underlying co-infections of human enterovirus D68 (HEV-D68) and bacteria (Group A Streptococcus and Streptococcus pneumoniae) in lung epithelial cells. Cell viability and gene expression changes were assessed over a 24-hour period. The results revealed significant cytopathic effect and distinct gene expression patterns. HEV-D68 infection alone induced stronger upregulation of mucin genes (MUC2, MUC5AC) and immune markers (TNFα and p38) compared to co-infections. In contrast, co-infections led to downregulation of sialic acid biosynthesis genes (CMAS, GNE, NANS), suggesting impaired receptor restoration and altered host-pathogen dynamics. These findings contribute to a deeper understanding of epithelial responses and highlight potential therapeutic targets.

The sustainability of commercial aquaculture production depends critically on prioritizing fish welfare management. Besides monitoring welfare parameters such as fish behaviour and water quality, fish stress level can also provide a reliable measure of the welfare status of farmed fish. Cortisol and 5 of its metabolites (5β-THF, cortisone, 5β-DHE, 5β-THE, β-cortolone) were previously identified by the authors as suitable stress biomarkers of farmed Atlantic salmon. Based on this knowledge, the present study aimed to investigate the time-related dynamics of these metabolites in plasma, skin mucus, bile and faeces over a 72 h- period. The objective was to determine the optimal sampling time for each matrix and to understand the clearance pathway of these metabolites following stress. An experiment was carried out using a total of 90 Atlantic salmon with an average weight of 438 (±132) g. The average sea temperature was 6.9 °C during the experimental period. A control group of 10 fish was first collected before the remaining 80 fish were submitted to a stress of netting and subsequent relocation into two separate cages. From each of these two stress groups, 10 fish were sampled at 1h, 2h, 4h, 6h and 12h, 24h, 48h, 72h after the stress event respectively. The concentrations of cortisol and its metabolites were measured at each of the sampling timepoint. The results demonstrated that plasma cortisol metabolites reached the highest concentration 4h after stress and remained elevated despite the slight decrease for the remaining timepoints. The peak level was observed at 12h post stress in skin mucus and 24h in bile and faeces. The findings suggest that these timepoints are the optimal for sampling Atlantic salmon post-smolt following stressful events in acute stress studies. Furthermore, the results reveal that analysing cortisol and its metabolites, both in free and conjugated forms, rather than free cortisol provides greater flexibility as their concentrations are less affected by sampling procedure. This study confirms the appropriateness of skin mucus and faeces as less-invasive sample matrices for fish stress evaluation and provides a basis for further developing low invasive tools for monitoring the welfare of farmed salmonid.

Stress assessment is crucial in aquaculture to ensure and improve the health and well-being of production animals including fish. The primary objective of this study was to utilize the assessment of fecal cortisol metabolites (FCMs) as a low-invasive stress determination method for farmed Atlantic salmon (Salmo salar L.) and to suggest an appropriate sampling timeframe for this measurement. Blood, mid-intestinal contents, and feces samples were collected before, during, and at 2 and 20 h after a stress-inducing event, namely, net cleaning. Plasma cortisol (PC) and its metabolite levels in the mid-intestinal contents (MICMs) and FCMs were assessed by an enzyme-linked immunosorbent assay (ELISA). The research reveals a distinctive temporal profile, with a sequential elevation in levels of PC, MICMs and FCMs in response to the effects of net cleaning. Peak FCMs levels were observed approximately 20 h after net cleaning and were significantly higher than peak PC levels (P < 0.05). The findings suggest that FCMs are a promising indicator for acute stress assessment. To enhance the understanding and improve the applicability of FCMs as stress indicators in fish farming practices the critical challenges regarding feces sampling and FCMs analyses are further discussed. Future research aimed at developing practical protocols and industry standards will emphasize method validation and include a greater number of sampling points as well as an expanded experimental period. This study signifies a crucial step toward understanding the role of FCMs as a reliable stress indicator in fish. It underscores the importance of accounting for the delayed and extended sampling patterns when assessing stress in aquatic settings. Moreover, it offers a less invasive and more labor-efficient approach for monitoring the overall health and welfare of salmonids than PC analysis, thereby promoting sustainability in this vital industry.

Monitoring stress levels of farmed Atlantic salmon (Salmo salar) is important to ensure fish welfare and optimize farm operations. Feces could be a promising matrix for assessing stress responses in fish, based on their properties of low-invasive sampling and allowing repeated sampling over time. Meanwhile, elevated levels of cortisol metabolites (CMs) in feces indicate the increases in plasma cortisol levels (PLA) after exposure to acute stress. However, the dynamics of fecal CMs following acute stress in Atlantic salmon remain unclear. In this study, a confinement stress involving chasing and crowding was conducted to investigate the responses of gastrointestinal CMs to an acute stressor in Atlantic salmon. The post-smolts, with an average weight of 155.21 g, were sampled before and at 30 min, 1.5, 6, 12, 18, 24, 36, and 48 h after the onset of stress. Blood and gastrointestinal contents from the stomach, proximal intestine, and distal intestine of each fish were collected and subsequently analyzed, using competitive enzyme-linked immunosorbent assay (ELISA). The results demonstrated that the pre-stress level of PLA was low (4.28 ± 6.13 ng/ml) and reached a peak within 30 min following stress. The levels of CMs in gastrointestinal contents from stomach (SCMs), proximal intestine (PCMs), and distal intestine (DCMs) in pre-stress group were 0.82 ± 0.50, 18.31 ± 6.14 and 16.04 ± 6.69 ng/g, respectively. Gastrointestinal CMs increased significantly within 30 min and the peak levels of SCMs (3.51 ± 3.75 ng/g), PCMs (68.19 ± 23.71 ng/g) and DCMs (65.67 ± 23.37 ng/g) were found at 1.5 h post-stress. The significant increases in PCMs and DCMs post-stress validate the biological relevance of measuring intestinal CMs for assessing acute stress responses in Atlantic salmon. No significant difference was noted between PCMs and DCMs across all samples, suggesting that intestinal contents can serve as a suitable matrix compared with feces when measuring the responses of CMs to acute stress. The time lag between the peak of PLA levels and their reflection in the intestinal contents exceeded 1 h, indicating that using intestinal contents as a matrix to assess stress levels in fish can extend and delay the sampling window. This study highlights valuable guidance for determining the optimal times to utilize intestinal contents for measuring stress responses, providing further insights into the dynamics of fecal CM following acute stress.

The common cold is the most frequent viral infectious disease of the upper respiratory tract with different intensities based on the serotype and the characteristics of the virus. Numerous human rhinoviruses have been identified and classified. Human rhinovirus 87 (HRV87), also known as enterovirus D68 (EV-D68), is one of the common viruses causing respiratory infections. In this study, a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay was developed, optimized, and validated for the detection of EV-D68. Method development also covers specificity, sensitivity, efficiency, and inter-and-intra-assay variations. Overall, this one-step qPCR assay will permit quantitative assessments of human enterovirus D68 RNA. • Enterovirus D68 is a reemerging viral agent causing respiratory infection. • RT-qPCR assay developed for detection of human enterovirus D68. • In this article validation to secure reproducibility is done according to MIQE guidelines.

In today's education landscape, the convergence of sustainable internationalization and digital proficiency is of heightened importance, particularly within sectors marked by extensive globalization, exemplified by biomedical laboratory science (BLS). The presence of foreign health and social workers in Norwegian hospitals accentuates the urgency of effective cross-cultural communication. The aftermath of the 2020 Coronavirus Pandemic further underscores the imperative of innovation, efficiency, and internationalization in medical laboratory science education. Addressing the challenges in current BLS education, this paper proposes a transformative approach that uses virtual or simulated environments to seamlessly bridge educational and workplace contexts. Through simulations, serious games, and virtual reality, educators can provide authentic, up-to-date learning experiences with heightened engagement. From physics to engineering, various disciplines already harness simulation-based learning for skill development. Within medical education, simulations advance diagnostic and technical competencies. This paper introduces a Unity3D-powered virtual biomedical lab, offering immersive technical process learning that augments understanding of workflows and equipment operations, promising to reshape biomedical laboratory science education profoundly.

Farmed Atlantic salmon (Salmo salar L.) are subject to a variety of stressors throughout production. Elevations of cortisol level in the blood are one of the major endocrine primary stress responses in vertebrates and are widely used as stress indicator. However, blood sampling is invasive and stressful procedures. Cortisol instantly released into the blood at sampling can easily interfere with the initial stress response of interest. Fecal corticoid metabolites (FCM) have been suggested for a less invasive assessment of stress in fish. In the present study, we evaluated stress responses by using plasma cortisol and FCM as stress indicators in Atlantic salmon. Atlantic salmon (with average weight 42 g) were exposed to 3 different stressors: 1) parr-smolt transformation; 2) infestation with salmon lice (Lepeophtheirus salmonis) for two-weeks; 3) infection with infectious salmon anaemia virus (ISAV) for four weeks. The results demonstrated that FCM levels correlated well with the plasma cortisol levels at single-point sampling during long-term stress (p < 0.05). Significant increases of both plasma cortisol and FCM were found two weeks after initiated 24 h light. Each tank was sampled twice, with around 40-min interval. The chasing during the first sampling was used as an acute stressor. The effects of sampling procedures on plasma cortisol and FCM levels are compared. Blood and feces were analyzed by an Enzyme-Linked Immunosorbent Assay (ELISA). Plasma cortisol and FCM levels increased within 40 min after fish perceived an acute stressor when the average weight of fish was below 100 g. Attenuated cortisol stress responses to acute stress were found after fish experiencing long-term stress. Collectively, FCM reflects changes in plasma cortisol and can be an alternative to analysis of plasma cortisol in Atlantic salmon, complementing evidence of using FCM as stress indicators for monitoring and improving fish welfare. The results highlight that standard sampling procedures and good experimental designs should be established to ensure robust and repeatable results in the study of stress based on the FCM measurement. Future study will investigate representative timepoints for FCM sampling, with particular attention to the types of stress and sizes of the fish.

We assessed effects of two-step debonding strategies in calf rearing systems with different types of prolonged cow-calf contact (CCC) on stress responses, health and performance of dairy cows and calves. Forty-eight Holstein Friesian cow-calf pairs had either: 1) full contact including suckling, where contact was reduced before weaning via fence-line separation at day 49 (FC-FS) (n = 10); 2) full contact, where contact was reduced at day 56 by fitting calves with a nose-flap (FC-NF) (n = 10); 3) partial contact (calves were housed in a pen adjacent to the cow area allowing physical contact on initiative of the dam but no suckling), where contact was reduced before weaning by moving the calf box from the wall to prevent physical contact at day 49 (PC-BW) (n = 6); 4) partial contact, where contact was reduced the week after weaning by moving the calf box away from the wall at day 63 (PC-AW) (n = 12); 5) no contact (calves were removed from dam directly after birth and housed in a calf barn), calves were weaned at day 56 (NC) (n = 10). Between weeks 7-10, we assessed physiological stress parameters, weight gain, and the health status of calves, plus general activity patterns based on accelerometer sensor data of cow-calf pairs before, during and after the debonding interventions. Additionally, calves were subjected to four consecutive behavioural tests (i.e. open field, novel object, voluntary human approach and involuntary human approach test) prior to permanent separation at day 70 and their behavioural responses were assessed via video recordings to assess fearfulness. Machine-harvested milk yields of cows were evaluated during weeks 6-12. Data were analyzed with (generalized) linear mixed models. Throughout the debonding period, FCNF calves had an impaired growth rate (P = 0.02). In weeks 6-9, FC-FS and FC-NF cows had lower machineharvested milk yields than PC-BW, PC-AW, and NC cows (P <= 0.01). We found no differences in responsiveness of calves to behavioural tests, except that NC calves exhibited more solitary play events compared to PC and FC calves in the novel object test (P = 0.002). Overall, our results imply that calves with partial CCC showed low stress responses to debonding, whereas abrupt weaning with a nose-flap during full contact seemed most stressful. Machine-harvested milk yield of FC cows seemed to recover once calves were weaned. More research into strategies to improve the process of debonding is warranted.

Objective:To investigate the therapeutic effect of post-auricular subperiosteal injection of methylprednisolone combined with ginkgo biloba injection and mouse nerve growth factor in sudden deafness with type 2 diabetesmellitus. To understand the effect of post-auricular subperiosteal injection of methylprednisolone on type 2 diabetesmellitus complicated with sudden deafness and its effect on blood-glucose level, and to explore a more effective and safe method for treating this special group of sudden deafness. Method: Total 84 patients suffered from type 2 diabetesmellitus with sudden deafness and treated in Shaanxi Provincial People's Hospital from March 2017 to June 2018 were randomly divided into experimental group(post-auricular subperiosteal injection of methylprednisolone+ginkgo biloba injection, mouse nerve growth factor)(n=48) and a control group(ginkgo biloba injection, mouse nerve growth factor)(n=36). Each group was divided into high frequency, low frequency and flat and total deafness group. Then to compare the clinical efficacy of the two groups and the difference of the fluctuation of blood glucose and HbA1c before treatment and 2 hours after treatment. Result:①The effective rate of treatment in the experimental group was 79.17%, higher than that in the control group(58.33%), P<0.05. The results indicated that the effect of post-auricular subperiosteal injection of methylprednisolone combined with ginkgo biloba injection and mouse nerve growth factor was effective in sudden deafness with type 2 diabetesmellitus. ②There was no significant difference in the fluctuation of blood glucose and HbA1c before treatment and 2 hours after treatment in the experimental group, and it indicated that this treatment can effectively avoid systemic side effects of steroid and ensure the safety of the treatment. Conclusion:Post-auricular subperiosteal injection of methylprednisolone combined with ginkgo biloba injection and mouse nerve growth factor is effective in patients with sudden deafness with type 2 diabetesmellitus, furthermore, blood glucose will not be affected by the using of steroid, and it will aviod systemic hormonal side effects.

Objective: To investigate the clinical value of the seven-item Eustachian Tube Dysfunction Questionnaire(ETDQ-7) in evaluating Eustachian tube dysfunction before and after treatment.Method: A retrospective analysis of 50 patients with Eustachian tube dysfunction diagnosed. All the patients were given chymotrypsin 4 000 IU and dexamethasone injection 5 mg by blowing through the Eustachian tube under nasal endoscopic guidance once daily for 3-6 consecutive days. At the same time, azelastine hydrochloride nasal spray and budesonide nasal spray were applied, 2 sprays each time, 2 times a day; oral Olongma drops, 3 ml each time, 3 times a day. ETDQ-7 was completed before and after treatment, and the results of ear endoscopy, pure tone audiometry, acoustic impedance test, and Eustachian tube function test were analyzed comprehensively. Result: The ETDQ-7 score(15.6±7.1) after treatment was significantly higher than that before treatment(23.1±6.5) points (P<0.05), and the difference was statistically significant. After treatment, all patients felt that aural fullness, tinnitus or discomfort, hearing loss and other symptoms were relieved. The tympanic membrane was observed to be better than before treatment. The tympanic effusion and tympanic membrane invagination were improved, which was in line with the change of ETDQ-7 score. Conclusion: ETDQ-7 has a good clinical value in the evaluation of Eustachian tube dysfunction before and after treatment. It is a reproducible and effective method for evaluating Eustachian tube dysfunction(ETD).

Pancreas disease (PD) is one of the most serious infectious diseases of salmon caused by salmonid alphavirus (SAV), and can be transmitted over distance in marine environments. Vaccination has already proven to be an important management tool for prevention and control of infectious diseases in profitable aquaculture. Currently, the inactivated whole-virus vaccine against PD is commercially available in Norway, however, its effectiveness in the field remains limited studied; lifetime protection has not been proven yet. In recent years, significant advances in molecular biology have led to the emergence of subunit vaccines. E2 protein is an envelope protein of SAV in Norway and supposed to be the carrier of neutralizing epitopes. Thus, E2 protein represents a potential candidate target for subunit vaccine-based immunotherapy against SAV. The aim of this study is to determine the natural infection induced humoral response against E2 protein in farmed salmon. Atlantic salmon reared in sea cage culture at the north western part of Norway was used in this study. Blood samples were collected monthly from March 2015 to Feb 2016. Diagnosis of SAV infection was based on the transcription-polymerase chain reaction PCR results and symptom on fishes. The serological reactivity was determined by an enzyme-linked immunosorbent assay (ELISA). A recombinant E2 protein was used as target antigen, and a recombinant ubiquitin protein was used as negative control in this study. A western blot (WB) assay was applied for the verification of specific binding. The serologic results demonstrated that no E2 specific antibody was identified in the plasma collected from March to August 2015. During August and September 2015, there was an outbreak of PD in the sea cage. In the heart tissues collected in August, the infection of SAV2 was documented by PCR assay. A significant elevated percentage of peripheral neutrophils were demonstrated during this period, which declined to the normal level afterwards. In plasma from salmon collected in September, one-month post outbreak SAV infection, a significant increase in serum antibodies against E2 protein was detected. Two months after infection, the detected antibody frequency remains 7 out of 10 samples, and the level of antibodies became relatively stable until February 2016 before slaughtering. The frequency of Antibody against E2 protein was nearly equal to the detected SAV2 infection rate. The specific bindings of salmon antibodies to the E2 protein were confirmed by the WB assay. These results demonstrate a natural infection of SAV2 induced humoral responses against E2 protein, which indicates that E2 protein can be a promising target for vaccine and diagnosis design. Furthermore, the antibodies from SAV2 infected salmon could react with SAV3, which indicates the potential cross protection of SAV3 whole virus vaccine. Further study is required to investigate into the actual protective effect of the humoral responses and to determine the targeted epitopes on E2 protein, and their correlation with fish survival. This will provide valuable information for the treatment of SAV caused salmon pancreas disease in the future.

Fish welfare is an important issue for growth of the aquaculture industry. Stress responses represent animal's natural reactions to challenging conditions and could be used as a welfare indicator. Cortisol level is relevant to fish welfare condition, and is a readily measured component of the primary stress response system. Generally, cortisol is measured by blood sampling. However, fish blood cortisol level could be instantly influenced by handling-stress at sampling. Fecal corticoid metabolites (FCM) are a mixture of several different metabolites with a wide range of polarities. Thus, feces could be promising alternative less handling-sensitive and non-invasive biological matrices for cortisol evaluation in Atlantic salmon. In this study we developed non-invasive method for determination of fecal corticoid metabolites in farmed Atlantic salmon (Saimo salar L) using enzyme-linked immunosorbent assay (ELISA).It was demonstrated that salmon FCM extracted from salmon feces is insoluble in non-polar solvents like diethyl ether, but well soluble in polar solvents like methanol. The proper extraction ratio could be one ml 100% methanol for 100 mu L, of the liquid part of salmon feces or 100 mg of the solid part. The FCM directly detected in unextracted liquid part of feces correlated well with the FCM extracted from both liquid and solid part of the corresponding samples, without significant difference. Thus, it is feasible to measure FCM directly in the liquid part of salmon feces without any extraction procedure.Then, we applied this assay for FCM analysis in the group of salmon that experienced salmon pancreas disease (PD) and amoebic gill disease (AGD). We demonstrated 1) both plasma cortisol and FCM increased significantly during the outbreak of inflammatory disease (P < 0.01). Plasma cortisol level was elevated from 28 +/- 40 ng/ml to 164.4 +/- 62.5 ng/ml, FCM from 14.4 +/- 13.2 ng/ml to 170.7 +/- 89.7 ng/ml 2) 'Growth and starvation has no significant impact on either cortisol or FCM level. 3) FCM correlated well with plasma cortisol level (P < 0.01). Furthermore, there seems more individual variation in plasma cortisol levels than in FCM levels.These results suggest FCM could be directly analyzed in liquid part of salmon feces without extraction. This directly detected FCM level could represent the total fecal FCM level and plasma cortisol level. This simple and non-invasive method makes FCM a proper indicator for salmon welfare. (C) 2017 Elsevier Ltd. All rights reserved.

This paper presents a novel green and cost-effective ballast water treatment system which will utilize waste heat from propulsion machinery for the destruction of microorganisms in the ballast water in a relatively short time. The high temperature recovered from propulsion machinery combined with the rapid destruction of microorganisms will make the new system more effective than the current similar Ballast Water Management Systems. The research will involve a combination of biological laboratory experiments, numerical simulations, and full scale machinery testing. The project has a potential to lead to the development of methods and knowledge for efficient energy utilization, effective destruction of microorganisms, and reliable methods for sampling and testing of water quality. The latest results obtained demonstrate that the proposed idea works efficiently and effectively, while offering a satisfactory verification with on-site biological experiments.

Brominated flame retardants (BFRs) are ubiquitous industrial chemicals likely to persistently exist in the environment, bioaccumulate in food chains, and even may cause adverse health effects in human. Borgundfjorden fjord system, an important spawning ground for the Norwegian coastal cod (Gadus morhua) stock, was contaminated by significant levels of pollutants such as BFRs, due to the local previous industrial activities. In this study, we demonstrated high level of the BFRs polybrominated biphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) in cod liver and gonad samples from Borgundfjorden using mass spectroscopy (MS) detectors by Norwegian National Institute of Nutrition and Seafood Research (NIFES). Acute embryo toxicity test was further conducted using fertilized cod eggs. The eggs were short-term exposed to serial dilutions of five BFRs mixtures, BDE-47, or PCB mixture Aroclor 1254. At a concentration 10 times that detected in cod liver, the mixture of the five BFRs significantly reduced the embryo survival rate (p <; 0.01). Correspondingly, at 224 μg/L, which was around 10 times of that detected in cod liver, BDE-47 exhibited obvious cod embryo toxicity (p <; 0.01). As a positive control, Aroclor 1254 significantly reduced the embryo survival rate at 400 and 1600 μg/L (p <;0.001). This experiment has laid the foundation for further research on environmentally hazardous impact on the reproductive capacity of aquatic organisms, which will directly influence the fish stocks growing potential and thereby the Norwegian fishery activity.

Cancer-testis antigens belonging to the MAGE family of genes, such as MAGEC2, are commonly and specifically expressed in Multiple Myeloma (MM) and are associated with a more aggressive clinical course and chemotherapy resistance. MAGEC2 is thought to be an excellent candidate for cancer immunotherapy; however, the biological role of MAGEC2 in MM has remained unclear. We investigated the biological role of MAGEC2 in myeloma cells determining the effect of MAGEC2 knockdown on proliferation and apoptosis. Loss of MAGEC2 resulted in reduced proliferation, viability, and anchorage-independent growth of myeloma cells irrespective of the functional status of TP53 (p53). The anti-proliferative effect of MAGEC2 silencing was due to a decrease of cells in the S phase, cell cycle delay at both G0/G1 and/or G2/M, and an increase in the sub-G0/G1 diploid population related to apoptotic cell death. Importantly, overexpression of short hairpin (sh)RNA-refractory MAGEC2 rescued the anti-proliferative effect of mRNA knockdown and protected cells from apoptotic cell death. Our findings support a TP53-independent role of MAGEC2 in promoting the survival of myeloma cells suggesting that MAGEC2-specific immunotherapies have the potential to eradicate the most malignant cells within the myeloma tumour bulk leading to durable clinical responses.

Multiple myeloma (MM) is the malignancy with the most frequent expression of the highly immunogenic cancer–testis antigens (CTA), and we have performed the first analysis of longitudinal expression, immunological properties, and fine specificity of CTA-specific antibody responses in MM.

Ballast water contains a variety of organisms including bacteria, viruses and the adult and larval stages of the many marine and coastal plants and animals. As such, it poses serious ecological, economic and health problems and has serious negative effects on the global environment. This paper presents a new efficient ballast water analysis and heat treatment system using waste heat recovery system on ships. The project demonstrates laboratory methods to verify killing efficiency of microorganisms in sea water exposed to heat treatment over a short period of time. Heating times were varied in a range from 20 seconds to 3 minutes. The microorganisms were measured using a flow cytometry instrument and fluorescence microscopy to detect living and dead organisms in untreated and treated water. Based on the biological analysis, a related heat treatment simulation was carried out to confirm the control method.

1 Department of Internal Medicine II, Oncology/Hematology/Bone Marrow Transplantation with the Section Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany 2 University Cancer Center Hamburg (Hubertus Wald Tumorzentrum), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany 3 Division of Clinical Pharmacology, Department of Internal Medicine, Ludwig-Maximilian University, 80336 Munich, Germany 4 Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany 5 Institute for Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany 6 Institute for Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany