Refine
Year of publication
Document Type
- Journal article (1422)
- Doctoral Thesis (799)
- Conference Proceeding (26)
- Book article / Book chapter (18)
- Review (16)
- Preprint (13)
- Book (5)
- Report (3)
- Master Thesis (2)
- Other (1)
Language
- English (1927)
- German (377)
- Multiple languages (2)
Keywords
- Biochemie (81)
- Taufliege (69)
- Drosophila (51)
- Physiologische Chemie (50)
- Genexpression (36)
- Biologie (34)
- Drosophila melanogaster (33)
- evolution (30)
- Biene (29)
- Maus (29)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (2306) (remove)
Sonstige beteiligte Institutionen
- Institut für Tierökologie und Tropenbiologie (2)
- Mildred-Scheel-Nachwuchszentrum (2)
- Ökologische Station Fabrikschleichach (2)
- Albert-Ludwigs-Universität Freiburg (1)
- Boehringer Ingelheim Pharma GmbH & Co. KG (1)
- Boston Children's Hospital (1)
- Center for Computational and Theoretical Biology (CCTB), Universität Würzburg (1)
- Chemical Biology Laboratory, National Cancer Institue, Frederick (USA) (1)
- Core Unit Systemmedizin (1)
- DNA Analytics Core Facility, Biocenter, University of Wuerzburg, Wuerzburg, Germany (1)
ResearcherID
- D-1221-2009 (1)
- J-8841-2015 (1)
- N-2030-2015 (1)
Breed predispositions to canine digital neoplasms are well known. However, there is currently no statistical analysis identifying the least affected breeds. To this end, 2912 canine amputated digits submitted from 2014–2019 to the Laboklin GmbH & Co. KG for routine diagnostics were statistically analyzed. The study population consisted of 155 different breeds (most common: 634 Mongrels, 411 Schnauzers, 197 Labrador Retrievers, 93 Golden Retrievers). Non-neoplastic processes were present in 1246 (43%), tumor-like lesions in 138 (5%), and neoplasms in 1528 cases (52%). Benign tumors (n = 335) were characterized by 217 subungual keratoacanthomas, 36 histiocytomas, 35 plasmacytomas, 16 papillomas, 12 melanocytomas, 9 sebaceous gland tumors, 6 lipomas, and 4 bone tumors. Malignant neoplasms (n = 1193) included 758 squamous cell carcinomas (SCC), 196 malignant melanomas (MM), 76 soft tissue sarcomas, 52 mast cell tumors, 37 non-specified sarcomas, 29 anaplastic neoplasms, 24 carcinomas, 20 bone tumors, and 1 histiocytic sarcoma. Predisposed breeds for SCC included the Schnauzer (log OR = 2.61), Briard (log OR = 1.78), Rottweiler (log OR = 1.54), Poodle (log OR = 1.40), and Dachshund (log OR = 1.30). Jack Russell Terriers (log OR = −2.95) were significantly less affected by SCC than Mongrels. Acral MM were significantly more frequent in Rottweilers (log OR = 1.88) and Labrador Retrievers (log OR = 1.09). In contrast, Dachshunds (log OR = −2.17), Jack Russell Terriers (log OR = −1.88), and Rhodesian Ridgebacks (log OR = −1.88) were rarely affected. This contrasted with the well-known predisposition of Dachshunds and Rhodesian Ridgebacks to oral and cutaneous melanocytic neoplasms. Further studies are needed to explain the underlying reasons for breed predisposition or “resistance” to the development of specific acral tumors and/or other sites.
A viral infection involves entry and replication of viral nucleic acid in a host organism, subsequently leading to biochemical and structural alterations in the host cell. In the case of SARS-CoV-2 viral infection, over-activation of the host immune system may lead to lung damage. Albeit the regeneration and fibrotic repair processes being the two protective host responses, prolonged injury may lead to excessive fibrosis, a pathological state that can result in lung collapse. In this review, we discuss regeneration and fibrosis processes in response to SARS-CoV-2 and provide our viewpoint on the triggering of alveolar regeneration in coronavirus disease 2019 (COVID-19) patients.
In vitro rearing of honeybee larvae is an established method that enables exact control and monitoring of developmental factors and allows controlled application of pesticides or pathogens. However, only a few studies have investigated how the rearing method itself affects the behavior of the resulting adult honeybees. We raised honeybees in vitro according to a standardized protocol: marking the emerging honeybees individually and inserting them into established colonies. Subsequently, we investigated the behavioral performance of nurse bees and foragers and quantified the physiological factors underlying the social organization. Adult honeybees raised in vitro differed from naturally reared honeybees in their probability of performing social tasks. Further, in vitro-reared bees foraged for a shorter duration in their life and performed fewer foraging trips. Nursing behavior appeared to be unaffected by rearing condition. Weight was also unaffected by rearing condition. Interestingly, juvenile hormone titers, which normally increase strongly around the time when a honeybee becomes a forager, were significantly lower in three- and four-week-old in vitro bees. The effects of the rearing environment on individual sucrose responsiveness and lipid levels were rather minor. These data suggest that larval rearing conditions can affect the task performance and physiology of adult bees despite equal weight, pointing to an important role of the colony environment for these factors. Our observations of behavior and metabolic pathways offer important novel insight into how the rearing environment affects adult honeybees.
Summary
Bees, like many other organisms, evolved an endogenous circadian clock, which enables them to foresee daily environmental changes and exactly time foraging flights to periods of floral resource availability. The social lifestyle of a honey bee colony has been shown to influence circadian behavior in nurse bees, which do not exhibit rhythmic behavior when they are nursing. On the other hand, forager bees display strong circadian rhythms. Solitary bees, like the mason bee, do not nurse their offspring and do not live in hive communities, but face the same daily environmental changes as honey bees. Besides their lifestyle mason and honey bees differ in their development and life history, because mason bees overwinter after eclosion as adults in their cocoons until they emerge in spring. Honey bees do not undergo diapause and have a relatively short development of a few weeks until they emerge. In my thesis, I present a comparison of the circadian clock of social honey bees (Apis mellifera) and solitary mason bees (Osmia bicornis and Osmia cornuta) on the neuroanatomical level and behavioral output level.
I firstly characterized in detail the localization of the circadian clock in the bee brain via the expression pattern of two clock components, namely the clock protein PERIOD (PER) and the neuropeptide Pigment Dispersing Factor (PDF), in the brain of honey bee and mason bee. PER is localized in lateral neuron clusters (which we called lateral neurons 1 and 2: LN1 and LN2) and dorsal neuron clusters (we called dorsal lateral neurons and dorsal neurons: DLN, DN), many glia cells and photoreceptor cells. This expression pattern is similar to the one in other insect species and indicates a common ground plan of clock cells among insects. In the LN2 neuron cluster with cell bodies located in the lateral brain, PER is co-expressed with PDF. These cells build a complex arborization network throughout the brain and provide the perfect structure to convey time information to brain centers, where complex behavior, e.g. sun-compass orientation and time memory, is controlled. The PDF arborizations centralize in a dense network (we named it anterio-lobular PDF hub: ALO) which is located in front of the lobula. In other insects, this fiber center is associated with the medulla (accessory medulla: AME). Few PDF cells build the ALO already in very early larval development and the cell number and complexity of the network grows throughout honey bee development. Thereby, dorsal regions are innervated first by PDF fibers and, in late larval development, the fibers grow laterally to the optic lobe and central brain. The overall expression pattern of PER and PDF are similar in adult social and solitary bees, but I found a few differences in the PDF network density in the posterior protocerebrum and the lamina, which may be associated with evolution of sociality in bees.
Secondly, I monitored activity rhythms, for which I developed and established a device to monitor locomotor activity rhythms of individual honey bees with contact to a mini colony in the laboratory. This revealed new aspects of social synchronization and survival of young bees with indirect social contact to the mini colony (no trophalaxis was possible). For mason bees, I established a method to monitor emergence and locomotor activity rhythms and I could show that circadian emergence rhythms are entrainable by daily temperature cycles. Furthermore, I present the first locomotor activity rhythms of solitary bees, which show strong circadian rhythms in their behavior right after emergence. Honey bees needed several days to develop circadian locomotor rhythms in my experiments. I hypothesized that honey bees do not emerge with a fully matured circadian system in the hive, while solitary bees, without the protection of a colony, would need a fully matured circadian clock right away after emergence. Several indices in published work and preliminary studies support my hypothesis and future studies on PDF expression in different developmental stages in solitary bees may provide hard evidence.
Commuting to work: Nucleolar long non-coding RNA control ribosome biogenesis from near and far
(2021)
Gene expression is an essential process for cellular growth, proliferation, and differentiation. The transcription of protein-coding genes and non-coding loci depends on RNA polymerases. Interestingly, numerous loci encode long non-coding (lnc)RNA transcripts that are transcribed by RNA polymerase II (RNAPII) and fine-tune the RNA metabolism. The nucleolus is a prime example of how different lncRNA species concomitantly regulate gene expression by facilitating the production and processing of ribosomal (r)RNA for ribosome biogenesis. Here, we summarise the current findings on how RNAPII influences nucleolar structure and function. We describe how RNAPII-dependent lncRNA can both promote nucleolar integrity and inhibit ribosomal (r)RNA synthesis by modulating the availability of rRNA synthesis factors in trans. Surprisingly, some lncRNA transcripts can directly originate from nucleolar loci and function in cis. The nucleolar intergenic spacer (IGS), for example, encodes nucleolar transcripts that counteract spurious rRNA synthesis in unperturbed cells. In response to DNA damage, RNAPII-dependent lncRNA originates directly at broken ribosomal (r)DNA loci and is processed into small ncRNA, possibly to modulate DNA repair. Thus, lncRNA-mediated regulation of nucleolar biology occurs by several modes of action and is more direct than anticipated, pointing to an intimate crosstalk of RNA metabolic events.
Background
Wilms tumor (WT) is the most common renal tumor in childhood. Among others, MYCN copy number gain and MYCN P44L and MAX R60Q mutations have been identified in WT. MYCN encodes a transcription factor that requires dimerization with MAX to activate transcription of numerous target genes. MYCN gain has been associated with adverse prognosis in different childhood tumors including WT. The MYCN P44L and MAX R60Q mutations, located in either the transactivating or basic helix-loop-helix domain, respectively, are predicted to be damaging by different pathogenicity prediction tools, but the functional consequences remain to be characterized.
Methods
We screened a large cohort of unselected WTs for MYCN and MAX alterations. Wild-type and mutant protein function were characterized biochemically, and we analyzed the N-MYC protein interactome by mass spectrometric analysis of N-MYC containing protein complexes.
Results
Mutation screening revealed mutation frequencies of 3% for MYCN P44L and 0.9% for MAX R60Q that are associated with a higher risk of relapse. Biochemical characterization identified a reduced transcriptional activation potential for MAX R60Q, while the MYCN P44L mutation did not change activation potential or protein stability. The protein interactome of N-MYC-P44L was likewise not altered as shown by mass spectrometric analyses of purified N-MYC complexes. Nevertheless, we could identify a number of novel N-MYC partner proteins, e.g. PEG10, YEATS2, FOXK1, CBLL1 and MCRS1, whose expression is correlated with MYCN in WT samples and several of these are known for their own oncogenic potential.
Conclusions
The strongly elevated risk of relapse associated with mutant MYCN and MAX or elevated MYCN expression corroborates their role in WT oncogenesis. Together with the newly identified co-expressed interactors they expand the range of potential biomarkers for WT stratification and targeting, especially for high-risk WT.
Serine/threonine kinase PknB and its corresponding phosphatase Stp are important regulators of many cell functions in the pathogen S. aureus. Genome-scale gene expression data of S. aureus strain NewHG (sigB\(^+\)) elucidated their effect on physiological functions. Moreover, metabolic modelling from these data inferred metabolic adaptations. We compared wild-type to deletion strains lacking pknB, stp or both. Ser/Thr phosphorylation of target proteins by PknB switched amino acid catabolism off and gluconeogenesis on to provide the cell with sufficient components. We revealed a significant impact of PknB and Stp on peptidoglycan, nucleotide and aromatic amino acid synthesis, as well as catabolism involving aspartate transaminase. Moreover, pyrimidine synthesis was dramatically impaired by stp deletion but only slightly by functional loss of PknB. In double knockouts, higher activity concerned genes involved in peptidoglycan, purine and aromatic amino acid synthesis from glucose but lower activity of pyrimidine synthesis from glucose compared to the wild type. A second transcriptome dataset from S. aureus NCTC 8325 (sigB\(^−\)) validated the predictions. For this metabolic adaptation, PknB was found to interact with CdaA and the yvcK/glmR regulon. The involved GlmR structure and the GlmS riboswitch were modelled. Furthermore, PknB phosphorylation lowered the expression of many virulence factors, and the study shed light on S. aureus infection processes.
We observed substantial differences in predicted Major Histocompatibility Complex II (MHCII) epitope presentation of SARS-CoV-2 proteins for different populations but only minor differences in predicted MHCI epitope presentation. A comparison of this predicted epitope MHC-coverage revealed for the early phase of infection spread (till day 15 after reaching 128 observed infection cases) highly significant negative correlations with the case fatality rate. Specifically, this was observed in different populations for MHC class II presentation of the viral spike protein (p-value: 0.0733 for linear regression), the envelope protein (p-value: 0.023), and the membrane protein (p-value: 0.00053), indicating that the high case fatality rates of COVID-19 observed in some countries seem to be related with poor MHC class II presentation and hence weak adaptive immune response against these viral envelope proteins. Our results highlight the general importance of the SARS-CoV-2 structural proteins in immunological control in early infection spread looking at a global census in various countries and taking case fatality rate into account. Other factors such as health system and control measures become more important after the early spread. Our study should encourage further studies on MHCII alleles as potential risk factors in COVID-19 including assessment of local populations and specific allele distributions.
Effects of climate change‐induced events on forest ecosystem dynamics of composition, function and structure call for increased long‐term, interdisciplinary and integrated research on biodiversity indicators, in particular within strictly protected areas with extensive non‐intervention zones. The long‐established concept of forest supersites generally relies on long‐term funds from national agencies and goes beyond the logistic and financial capabilities of state‐ or region‐wide protected area administrations, universities and research institutes.
We introduce the concept of data pools as a smaller‐scale, user‐driven and reasonable alternative to co‐develop remote sensing and forest ecosystem science to validated products, biodiversity indicators and management plans. We demonstrate this concept with the Bohemian Forest Ecosystem Data Pool, which has been established as an interdisciplinary, international data pool within the strictly protected Bavarian Forest and Šumava National Parks and currently comprises 10 active partners. We demonstrate how the structure and impact of the data pool differs from comparable cases.
We assessed the international influence and visibility of the data pool with the help of a systematic literature search and a brief analysis of the results. Results primarily suggest an increase in the impact and visibility of published material during the life span of the data pool, with highest visibilities achieved by research conducted on leaf traits, vegetation phenology and 3D‐based forest inventory.
We conclude that the data pool results in an efficient contribution to the concept of global biodiversity observatory by evolving towards a training platform, functioning as a pool of data and algorithms, directly communicating with management for implementation and providing test fields for feasibility studies on earth observation missions.
Climate plants are critical to prevent global warming as all efforts to save carbon dioxide are too slow and climate disasters on the rise. For best carbon dioxide harvesting we compare algae, trees and crop plants and use metagenomic analysis of environmental samples. We compare different pathways, carbon harvesting potentials of different plants as well as synthetic modifications including carbon dioxide flux balance analysis. For implementation, agriculture and modern forestry are important.
Tree species diversity is important to maintain saproxylic beetle diversity in managed forests. Yet, knowledge about the conservational importance of single tree species and implications for forest management and conservation practices are lacking.
We exposed freshly cut branch‐bundles of 42 tree species, representing tree species native and non‐native to Europe, under sun‐exposed and shaded conditions for 1 year. Afterwards, communities of saproxylic beetles were reared ex situ for 2 years. We tested for the impact of tree species and sun exposure on alpha‐, beta‐, and gamma‐diversity as well as composition of saproxylic beetle communities. Furthermore, the number of colonised tree species by each saproxylic beetle species was determined.
Tree species had a lower impact on saproxylic beetle communities compared to sun exposure. The diversity of saproxylic beetles varied strongly among tree species, with highest alpha‐ and gamma‐diversity found in Quercus petraea. Red‐listed saproxylic beetle species occurred ubiquitously among tree species. We found distinct differences in the community composition of broadleaved and coniferous tree species, native and non‐native tree species as well as sun‐exposed and shaded deadwood.
Our study enhances the understanding of the importance of previously understudied and non‐native tree species for the diversity of saproxylic beetles. To improve conservation practices for saproxylic beetles and especially red‐listed species, we suggest a stronger incorporation of tree species diversity and sun exposure of into forest management strategies, including the enrichment of deadwood from native and with a specific focus on locally rare or silviculturally less important tree species.
Plant traits mediate the effects of climate on phytophagous beetle diversity on Mt. Kilimanjaro
(2021)
Patterns of insect diversity along elevational gradients are well described in ecology. However, it remains little tested how variation in the quantity, quality, and diversity of food resources influence these patterns. Here we analyzed the direct and indirect effects of climate, food quantity (estimated by net primary productivity), quality (variation in the specific leaf area index, leaf nitrogen to phosphorus and leaf carbon to nitrogen ratio), and food diversity (diversity of leaf traits) on the species richness of phytophagous beetles along the broad elevation and land use gradients of Mt. Kilimanjaro, Tanzania. We sampled beetles at 65 study sites located in both natural and anthropogenic habitats, ranging from 866 to 4,550 m asl. We used path analysis to unravel the direct and indirect effects of predictor variables on species richness. In total, 3,154 phytophagous beetles representing 19 families and 304 morphospecies were collected. We found that the species richness of phytophagous beetles was bimodally distributed along the elevation gradient with peaks at the lowest (˜866 m asl) and upper mid-elevations (˜3,200 m asl) and sharply declined at higher elevations. Path analysis revealed temperature- and climate-driven changes in primary productivity and leaf trait diversity to be the best predictors of changes in the species richness of phytophagous beetles. Species richness increased with increases in mean annual temperature, primary productivity, and with increases in the diversity of leaf traits of local ecosystems. Our study demonstrates that, apart from temperature, the quantity and diversity of food resources play a major role in shaping diversity gradients of phytophagous insects. Drivers of global change, leading to a change of leaf traits and causing reductions in plant diversity and productivity, may consequently reduce the diversity of herbivore assemblages.
Cyanine dyes are exceptionally useful probes for a range of fluorescence-based applications, but their photon output can be limited by trans-to-cis photoisomerization. We recently demonstrated that appending a ring system to the pentamethine cyanine ring system improves the quantum yield and extends the fluorescence lifetime. Here, we report an optimized synthesis of persulfonated variants that enable efficient labeling of nucleic acids and proteins. We demonstrate that a bifunctional sulfonated tertiary amide significantly improves the optical properties of the resulting bioconjugates. These new conformationally restricted cyanines are compared to the parent cyanine derivatives in a range of contexts. These include their use in the plasmonic hotspot of a DNA-nanoantenna, in single-molecule Förster-resonance energy transfer (FRET) applications, far-red fluorescence-lifetime imaging microscopy (FLIM), and single-molecule localization microscopy (SMLM). These efforts define contexts in which eliminating cyanine isomerization provides meaningful benefits to imaging performance.
Sex determination (SD) is a highly diverse and complex mechanism. In vertebrates, one of the first morphological differences between the sexes is the timing of initiation of the first meiosis, where its initiation occurs first in female and later in male. Thus, SD is intimately related to the responsiveness of the germ cells to undergo meiosis in a sex-specific manner. In some vertebrates, it has been reported that the timing for meiosis entry would be under control of retinoic acid (RA), through activation of Stra8. In this study, we used a fish model species for sex determination and lacking the stra8 gene, the Japanese medaka (Oryzias latipes), to investigate the connection between RA and the sex determination pathway. Exogenous RA treatments act as a stress factor inhibiting germ cell differentiation probably by activation of dmrt1a and amh. Disruption of the RA degrading enzyme gene cyp26a1 induced precocious meiosis and oogenesis in embryos/hatchlings of female and even some males. Transcriptome analyzes of cyp26a1–/–adult gonads revealed upregulation of genes related to germ cell differentiation and meiosis, in both ovaries and testes. Our findings show that germ cells respond to RA in a stra8 independent model species. The responsiveness to RA is conferred by sex-related genes, restricting its action to the sex differentiation period in both sexes.
Input‐driven, modern agriculture is commonly associated with large‐scale threats to biodiversity, the disruption of ecosystem services and long‐term risks to food security and human health. A switch to more sustainable yet highly productive farming practices seems unavoidable. However, an integrative evaluation of targeted management schemes at field and landscape scales is currently lacking. Furthermore, the often‐disproportionate influence of soil conditions and agrochemicals on yields may mask the benefits of biodiversity‐driven ecosystem services.
Here, we used a real‐world ecosystem approach to identify sustainable management practices for enhanced functional biodiversity and yield on 28 temperate wheat fields. Using path analysis, we assessed direct and indirect links between soil, crop and landscape management with natural enemies and pests, as well as follow‐on effects on yield quantity and quality. A paired‐field design with a crossed insecticide‐fertilizer experiment allowed us to control for the relative influence of soil characteristics and agrochemical inputs.
We demonstrate that biodiversity‐enhancing management options such as reduced tillage, crop rotation diversity and small field size can enhance natural enemies without relying on agrochemical inputs. Similarly, we show that in this system controlling pests and weeds by agrochemical means is less relevant than expected for final crop productivity.
Synthesis and applications. Our study highlights soil, crop and landscape management practices that can enhance beneficial biodiversity while reducing agrochemical usage and negative environmental impacts of conventional agriculture. The diversification of cropping systems and conservation tillage are practical measures most farmers can implement without productivity losses. Combining local measures with improved landscape management may also strengthen the sustainability and resilience of cropping systems in light of future global change.
Although macroecology is a well‐established field, much remains to be learned about the large‐scale variation of fungal traits. We conducted a global analysis of mean fruit body size of 59 geographical regions worldwide, comprising 5340 fungal species exploring the response of fruit body size to latitude, resource availability and temperature. The results showed a hump‐shaped relationship between mean fruit body size and distance to the equator. Areas with large fruit bodies were characterised by a high seasonality and an intermediate mean temperature. The responses of mutualistic species and saprotrophs were similar. These findings support the resource availability hypothesis, predicting large fruit bodies due to a seasonal resource surplus, and the thermoregulation hypothesis, according to which small fruit bodies offer a strategy to avoid heat and cold stress and therefore occur at temperature extremes. Fruit body size may thus be an adaptive trait driving the large‐scale distribution of fungal species.
Fungus-farming within galleries in the xylem of trees has evolved independently in at least twelve lineages of weevils (Curculionidae: Scolytinae, Platypodinae) and one lineage of ship-timber beetles (Lymexylidae). Jointly these are termed ambrosia beetles because they actively cultivate nutritional “ambrosia fungi” as their main source of food. The beetles are obligately dependent on their ambrosia fungi as they provide them a broad range of essential nutrients ensuring their survival in an extremely nutrient-poor environment. While xylem is rich in carbon (C) and hydrogen (H), various elements essential for fungal and beetle growth, such as nitrogen (N), phosphorus (P), sulfur (S), potassium (K), calcium (Ca), magnesium (Mg), and manganese (Mn) are extremely low in concentration. Currently it remains untested how both ambrosia beetles and their fungi meet their nutritional requirements in this habitat. Here, we aimed to determine for the first time if galleries of ambrosia beetles are generally enriched with elements that are rare in uncolonized xylem tissue and whether these nutrients are translocated to the galleries from the xylem by the fungal associates. To do so, we examined natural galleries of three ambrosia beetle species from three independently evolved farming lineages, Xyleborinus saxesenii (Scolytinae: Xyleborini), Trypodendron lineatum (Scolytinae: Xyloterini) and Elateroides dermestoides (Lymexylidae), that cultivate unrelated ambrosia fungi in the ascomycete orders Ophiostomatales, Microascales, and Saccharomycetales, respectively. Several elements, in particular Ca, N, P, K, Mg, Mn, and S, were present in high concentrations within the beetles’ galleries but available in only very low concentrations in the surrounding xylem. The concentration of elements was generally highest with X. saxesenii, followed by T. lineatum and E. dermestoides, which positively correlates with the degree of sociality and productivity of brood per gallery. We propose that the ambrosia fungal mutualists are translocating essential elements through their hyphae from the xylem to fruiting structures they form on gallery walls. Moreover, the extremely strong enrichment observed suggests recycling of these elements from the feces of the insects, where bacteria and yeasts might play a role.
The aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.006) and NF-H (p = 0.0002) levels after TBI were significantly higher than those in cardiovascular controls. Immunohistochemical staining against MBP and against NF-H was performed on cortical and subcortical samples from also biochemically investigated cases (5 TBI cases/5 controls). Compared to the controls, the TBI cases showed a visually reduced staining reaction against MBP or repeatedly ruptured neurofilaments against NF-H. Immunocytochemical tests showed MBP-positive phagocytizing macrophages in CSF with a survival time of > 24 h. In addition, numerous TMEM119-positive microglia could be detected with different degrees of staining intensity in the CSF of trauma cases. As a result, we were able to document that elevated levels of MBP and NF-H in the CSF should be considered as useful neuroinjury biomarkers of traumatic brain injury.
The Glycosylphosphatidylinositol Anchor: A Linchpin for Cell Surface Versatility of Trypanosomatids
(2021)
The use of glycosylphosphatidylinositol (GPI) to anchor proteins to the cell surface is widespread among eukaryotes. The GPI-anchor is covalently attached to the C-terminus of a protein and mediates the protein’s attachment to the outer leaflet of the lipid bilayer. GPI-anchored proteins have a wide range of functions, including acting as receptors, transporters, and adhesion molecules. In unicellular eukaryotic parasites, abundantly expressed GPI-anchored proteins are major virulence factors, which support infection and survival within distinct host environments. While, for example, the variant surface glycoprotein (VSG) is the major component of the cell surface of the bloodstream form of African trypanosomes, procyclin is the most abundant protein of the procyclic form which is found in the invertebrate host, the tsetse fly vector. Trypanosoma cruzi, on the other hand, expresses a variety of GPI-anchored molecules on their cell surface, such as mucins, that interact with their hosts. The latter is also true for Leishmania, which use GPI anchors to display, amongst others, lipophosphoglycans on their surface. Clearly, GPI-anchoring is a common feature in trypanosomatids and the fact that it has been maintained throughout eukaryote evolution indicates its adaptive value. Here, we explore and discuss GPI anchors as universal evolutionary building blocks that support the great variety of surface molecules of trypanosomatids.
Persistence has evolved as a potent survival strategy to overcome adverse environmental conditions. This capability is common to almost all bacteria, including all human bacterial pathogens and likely connected to chronic infections caused by some of these pathogens. Although the majority of a bacterial cell population will be killed by the particular stressors, like antibiotics, oxygen and nitrogen radicals, nutrient starvation and others, a varying subpopulation (termed persisters) will withstand the stress situation and will be able to revive once the stress is removed. Several factors and pathways have been identified in the past that apparently favor the formation of persistence, such as various toxin/antitoxin modules or stringent response together with the alarmone (p)ppGpp. However, persistence can occur stochastically in few cells even of stress-free bacterial populations. Growth of these cells could then be induced by the stress conditions. In this review, we focus on the persister formation of human intracellular bacterial pathogens, some of which belong to the most successful persister producers but lack some or even all of the assumed persistence-triggering factors and pathways. We propose a mechanism for the persister formation of these bacterial pathogens which is based on their specific intracellular bipartite metabolism. We postulate that this mode of metabolism ultimately leads, under certain starvation conditions, to the stalling of DNA replication initiation which may be causative for the persister state.