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Schriftenreihe
Sonstige beteiligte Institutionen
- Fraunhofer-Institut für Silicatforschung ISC (5)
- Helmholtz Institute for RNA-based Infection Research (HIRI) (5)
- Technische Hochschule Nürnberg Georg Simon Ohm (3)
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- Universitätsklinikum Münster (2)
ResearcherID
- B-1911-2015 (1)
- B-4606-2017 (1)
- C-2593-2016 (1)
- D-1250-2010 (1)
- I-5818-2014 (1)
- J-8841-2015 (1)
- M-1240-2017 (1)
- N-2030-2015 (1)
- N-3741-2015 (1)
EU-Project number / Contract (GA) number
- 311781 (1)
- 320377 (1)
- EU (FP7/ 2007-2013) (1)
This dissertation contributes to the empirical analysis of economic development. The continuing poverty in many Sub-Saharan-African countries as well as the declining trend in growth in the advanced economies that was initiated around the turn of the millennium raises a number of new questions which have received little attention in recent empirical studies. Is culture a decisive factor for economic development? Do larger financial markets trigger positive stimuli with regard to incomes, or is the recent increase in their size in advanced economies detrimental to economic growth? What causes secular stagnation, i.e. the reduction in growth rates of the advanced economies observable over the past 20 years? What is the role of inequality in the growth process, and how do governmental attempts to equalize the income distribution affect economic development? And finally: Is the process of democratization accompanied by an increase in living standards? These are the central questions of this doctoral thesis.
To facilitate the empirical analysis of the determinants of economic growth, this dissertation introduces a new method to compute classifications in the field of social sciences. The approach is based on mathematical algorithms of machine learning and pattern recognition. Whereas the construction of indices typically relies on arbitrary assumptions regarding the aggregation strategy of the underlying attributes, utilization of Support Vector Machines transfers the question of how to aggregate the individual components into a non-linear optimization problem.
Following a brief overview of the theoretical models of economic growth provided in the first chapter, the second chapter illustrates the importance of culture in explaining the differences in incomes across the globe. In particular, if inhabitants have a lower average degree of risk-aversion, the implementation of new technology proceeds much faster compared with countries with a lower tendency towards risk. However, this effect depends on the legal and political framework of the countries, their average level of education, and their stage of development.
The initial wealth of individuals is often not sufficient to cover the cost of investments in both education and new technologies. By providing loans, a developed financial sector may help to overcome this shortage. However, the investigations in the third chapter show that this mechanism is dependent on the development levels of the economies. In poor countries, growth of the financial sector leads to better education and higher investment levels. This effect diminishes along the development process, as intermediary activity is increasingly replaced by speculative transactions. Particularly in times of low technological innovation, an increasing financial sector has a negative impact on economic development. In fact, the world economy is currently in a phase of this kind. Since the turn of the millennium, growth rates in the advanced economies have experienced a multi-national decline, leading to an intense debate about "secular stagnation" initiated at the beginning of 2015. The fourth chapter deals with this phenomenon and shows that the growth potentials of new technologies have been gradually declining since the beginning of the 2000s.
If incomes are unequally distributed, some individuals can invest less in education and technological innovations, which is why the fifth chapter identifies an overall negative effect of inequality on growth. This influence, however, depends on the development level of countries. While the negative effect is strongly pronounced in poor economies with a low degree of equality of opportunity, this influence disappears during the development process. Accordingly, redistributive polices of governments exert a growth-promoting effect in developing countries, while in advanced economies, the fostering of equal opportunities is much more decisive.
The sixth chapter analyzes the growth effect of the political environment and shows that the ambiguity of earlier studies is mainly due to unsophisticated measurement of the degree of democratization. To solve this problem, the chapter introduces a new method based on mathematical algorithms of machine learning and pattern recognition. While the approach can be used for various classification problems in the field of social sciences, in this dissertation it is applied for the problem of democracy measurement. Based on different country examples, the chapter shows that the resulting SVMDI is superior to other indices in modeling the level of democracy. The subsequent empirical analysis emphasizes a significantly positive growth effect of democracy measured via SVMDI.
We investigate transport measurements on all II-VI semiconductor resonant tunneling diodes (RTDs). Being very versatile, the dilute magnetic semiconductor (DMS) system (Zn,Be,Mn,Cd)Se is a perfect testbed for various spintronic device designs, as it allows for separate control of electrical and magnetic properties. In contrast to the ferromagnetic semiconductor (Ga,Mn)As, doping ZnSe with Mn impurities does not alter the electrical properties of the semiconductor, as the magnetic dopant is isoelectric in the ZnSe host.
A comprehensive approach for currency crises theories stressing the role of the anchor country
(2008)
The approach is based on the finding that new generations of currency crises theories always had developed ex post after popular currency crises. Discussing the main theories of currency crises shows their disparity: The First Generation of currency crises models argues based on the assumption of a chronic budget deficit that is being monetized by the domestic central bank. The result is a trade-off between an expansionary monetary policy that is focused on the internal economic balance and a fixed exchange rate which is depending on the rules of interest parity and purchasing power parity. This imbalance inevitably results in a currency crisis. Altogether, this theory argues with a disrupted external balance on the foreign exchange market. Second Generation currency crises models on the other side focus on the internal macroeconomic balance. The stability of a fixed exchange rate is depending on the economic benefit of the exchange rate system in relation to the social costs of maintaining it. As soon as social costs are increasing and showing up in deteriorating fundamentals, this leads to a speculative attack on the fixed exchange rate system. The term Third Generation of currency crises finally summarizes a variety of currency crises theories. These are also arguing psychologically to explain phenomena as contagion and spill-over effects to rationalize crises detached from the fundamental situation. Apart from the apparent inconsistency of the main theories of currency crises, a further observation is that these explanations focus on the crisis country only while international monetary transmission effects are left out of consideration. These however are a central parameter for the stability of fixed exchange rate systems, in exchange rate theory as well as in empirical observations. Altogether, these findings provide the motivation for developing a theoretical approach which integrates the main elements of the different generations of currency crises theories and which integrates international monetary transmission. Therefore a macroeconomic approach is chosen applying the concept of the Monetary Conditions Index (MCI), a linear combination of the real interest rate and the real exchange rate. This index firstly is extended for international monetary influences and called MCIfix. MCIfix illustrates the monetary conditions required for the stability of a fixed exchange rate system. The central assumption of this concept is that the uncovered interest parity is maintained. The main conclusion is that the MCIfix only depends on exogenous parameters. In a second step, the analysis integrates the monetary policy requirements for achieving an internal macroeconomic stability. By minimizing a loss function of social welfare, a MCI is derived which pictures the economically optimal monetary policy MCIopt. Instability in a fixed exchange rate system occurs as soon as the monetary conditions for an internal and external balance are deviating. For discussing macroeconomic imbalances, the central parameters determining the MCIfix (and therefore the relation of MCIfix to MCIopt) are discussed: the real interest rate of the anchor country, the real effective exchange rate and a risk premium. Applying this theory framework, four constellations are discussed where MCIfix and MCIopt fall apart in order to show the central bank’s possibilities for reacting and the consequences of that behaviour. The discussion shows that the integrative approach manages to incorporate the central elements of traditional currency crises theories and that it includes international monetary transmission instead of reducing the discussion on an inconsistent domestic monetary policy. The theory framework for fixed exchange rates is finally applied in four case studies: the currency crises in Argentina, the crisis in the Czech Republic, the Asian currency crisis and the crisis of the European Monetary System. The case studies show that the developed monetary framework achieves integration of different generations of crises theories and that the monetary policy of the anchor country plays a decisive role in destabilising fixed exchange rate systems.
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.
The greatest problems faced during the 21st century is climate change which is a big threat to food security due to increasing number of people. The increase in extreme weather events, such as drought and heat, makes it difficult to cultivate conventional crops that are not stress tolerant. As a result, increasing irrigation of arable land leads to additional salinization of soils with plant-toxic sodium and chloride ions. Knowledge about the adaptation strategies of salt-tolerant plants to salt stress as well as detailed knowledge about the control of transpiration water loss of these plants are therefore important to guarantee productive agriculture in the future. In the present study, I have characterized salt sensitive and salt tolerant plant species at physiological, phenotypic and transcriptomic level under short (1x salt) and long-time (3x) saline growth conditions. Two approaches used for long-time saline growth conditions (i.e increasing saline conditions (3x salt) and constant high saline conditions (3x 200 mM salt) were successfully developed in the natural plant growth medium i.e soil. Salt sensitive plants, A. thaliana, were able to survive and successfully set seeds at the toxic concentrations on the increasing saline growth mediums, with minor changes in the phenotype. However, under constant high saline conditions they could not survive. This was due to keeping low potassium, and high salt ions (sodium and chloride) in the photosynthetic tissue i.e leaf. Similarly, high potassium and low salt ions in salt tolerant T. salsuginea on both saline environments were the key for survival of this plant species. Being salt tolerant, T. salsuginea always kept high potassium levels and low sodium (during 1x) and chloride levels (during both 1x and 3x) in the leaf tissue.
A strict control over transpirational water loss via stomata (formed by pair of guard cells) is important to maintain plant water balance. Aperture size of the stomata is regulated by the turgidity of the guard cells. More turgid the guard cells, bigger the apertures are and hence more transpiration. Under osmotic stress, the water loss is reduced which was evident in the salt sensitive A. thaliana plants under both short and long-time saline growth conditions. As the osmotic stress was only increased during long time saline growth conditions in T. salsuginea therefore, water loss was also decreased only under these saline conditions. Environmental CO2 assimilation also takes place via stomata in plants which then is used for photosynthesis. Stomatal apertures also influence CO2 assimilation. As the light absorbing photosynthetic pigments were more affected in A. thaliana, therefore photosynthetic activity of the whole plant was also reduced. Similarly, both short and long-time saline growth conditions also reduced the effective quantum yield of A. thaliana guard cells. Growth of the plant is dependent on energy which comes from photosynthesis. Reduced environmental CO2 assimilation would affect photosynthesis and hence growth, which was clearly observed in A. thaliana guard cells under long-time saline growth conditions.
Major differences in both guard cells types were observed in their chloride and potassium levels. Energy Dispersive X-Ray Analysis (EDXA) suggested strict control of chloride accumulation in T. salsuginea guard cells as the levels remain unchanged under all conditions. Similarly, use of sodium in place of potassium for osmotic adjustments seems to be dependent on Na+/K+ rations in both guard cell types. Increased salt ions and reduced potassium levels in A. thaliana guard cells posed negative effect on photochemistry which in turn increased ROS metabolism and reduced energy related pathways at transcriptomic level in this plant species. Moreover, photosynthesis was strongly affected in A. thaliana guard cells both at transcriptomic and physiological levels. Similarly, global phytohormones induced changes were more evident in A. thaliana guard cells especially on 3x salt medium. Among all phytohormones, genes under the control of auxin were more differentially expressed in A. thaliana guard cells which suggests wide changes in growth and development in this plant species under salinity.
Phytohormone, ABA is vital for closing the stomata under abiotic stress conditions. Increased levels of ABA during saline conditions led to efflux of potassium and counter anions (chloride, malate, nitrate) from the guard cells which caused the outward flow of water and hence reduction in turgor pressure. Reduced turgor pressure led to reduced water loss and CO2 assimilation especially in A. thaliana. Guard cells of both plant species synthesized ABA during saline conditions which was reflected from transcriptomic data and ABA quantification in the guard cells. ABA induced signaling in both plant species varied at the ABA receptor (PYL/PYR) levels where totally contrasting responses were observed. PYL2, PYL8 and PYL9 were specific to A. thaliana, furthermore, PYL2 was found to be differentially expressed only under 3x salt growth conditions thus suggesting its role during long term salt stress in this plant species. Protein phosphatases, which negatively regulate ABA signaling on one hand and act as ABA sensor on the other hand were found to be more differentially expressed in A. thaliana than T. salsuginea guard cells, which suggests their diverse role in both plant species under saline conditions. Differential expression of more ABA signaling players in long time saline conditions was prominent which could be because of darkness, as it is well known that rapid closure of stomata under dark conditions require ABA signaling. Moreover, representation of these components in dark also suggests that plants become more sensitive to dark under saline conditions which is also evident from the transpiration rates.
Altogether, increased salt ions in A. thaliana guard cells and leaves led to pigment degradation and ABA induced reduction in transpiration which in turn influenced its growth. In contrast, T. salsuginea is the salt excluder and therefore keeps low levels of salt ions especially the chloride both in leaves and guard cells which mildly affects its growth. Guard cells of A. thaliana encounter severe energy problems at physiological and transcriptomic level. Main differences in the ABA signalling between both plant species were observed at the ABA receptor level.
The superconducting properties of complex materials like the recently discovered iron-pnictides or strontium-ruthenate are often governed by multi-orbital effects. In order to unravel the superconductivity of those materials, we develop a multi-orbital implementation of the functional renormalization group and study the pairing states of several characteristic material systems. Starting with the iron-pnictides, we find competing spin-fluctuation channels that become attractive if the superconducting gap changes sign between the nested portions of the Fermi surface. Depending on material details like doping or pnictogen height, these spin fluctuations then give rise to $s_{\pm}$-wave pairing with or without gap nodes and, in some cases, also change the symmetry to $d$-wave. Near the transition from nodal $s_{\pm}$-wave to $d$-wave pairing, we predict the occurrence of a time-reversal symmetry-broken $(s+id)$-pairing state which avoids gap nodes and is therefore energetically favored. We further study the electronic instabilities of doped graphene, another fascinating material which has recently become accessible and which can effectively be regarded as multi-orbital system. Here, the hexagonal lattice structure assures the degeneracy of two $d$-wave pairing channels, and the system then realizes a chiral $(d+id)$-pairing state in a wide doping range around van-Hove filling. In addition, we also find spin-triplet pairing as well as an exotic spin-density wave phase which both become leading if the long-ranged hopping or interaction parameters are slightly modified, for example, by choosing different substrate materials. Finally, we consider the superconducting state of strontium-ruthenate, a possible candidate for chiral spin-triplet pairing with fascinating properties like the existence of half-quantum vortices obeying non-Abelian statistics. Using a microscopic three orbital description including spin-orbit coupling, we demonstrate that ferromagnetic fluctuations are still sufficient to induce this $\bs{\hat{z}}(p_x\pm ip_y)$-pairing state. The resulting superconducting gap reveals strong anisotropies on the $d_{xy}$-dominated Fermi-surface pocket and nearly vanishes on the other remaining two pockets.
A closer look at long-established drugs: enantioselective protein binding and stability studies
(2023)
The aim of this work was to investigate older, established drugs. The extent of the protein binding of chiral ephedra alkaloids to AGP and of ketamine to albumin was determined. Since enantiomers of these drugs are individual available, the focus was on possible enantioselective binding and structural moieties involved in the binding.
Previously published work suggested that ephedrine and pseudoephedrine can bind stereoselectively to proteins other than albumin in serum. For the determination of the extent of protein binding, the established ultrafiltration with subsequent chiral CE analysis was used. To determine the influence of basicity on binding, the drugs methylephedrine and norephedrine were also analyzed. Drug binding to AGP increased with increasing basicity as follows: norephedrine < methylephedrine < ephedrine < pseudoephedrine. pKaff was determined both graphically using the Klotz plot and mathematical indicating a low affinity of the ephedra alkaloids to AGP. Using STD-NMR spectroscopy experiments the aromatic protons and the C-CH3 side chain were shown to be most strongly involved in binding, which could be confirmed by molecular docking experiments in more detail. For all drugs, van der Waals-, π π , cationic interactions, hydrogen bonds, and a formation of a salt bridge were observed. The individual enantiomers showed no significant differences and thus the binding of ephedra alkaloids to AGP is not significant.
In contrast to the ephedra alkaloids, the possible enantioselective binding to albumin was investigated for R and S ketamine. Again, ultrafiltration followed by CE analysis was performed. The binding of ketamine to one main binding site could be identified. A non-linear fit was used for the determination of pKaff. Using the NMR methods STD-NMR, waterLOGSY-NMR, and CPMG-NMRspectroscopy: the aromatic protons as well as the protons of the NCH3 methyl group showed the largest signal intensity changes, while the cyclohexanone protons showed the smallest changes. pKaff was also determined by the change in the chemical shift at different drug-protein ratios. These obtained values confirm the values obtained from ultrafiltration. Based on this, ketamine is classified as a low-affinity ligand to albumin. There were no significant differences between the individual enantiomers and thus the binding of ketamine to albumin is not a stereoselective process.
Using statistical design of experiments an efficient chiral CE method for determining the extent of protein binding of R and S ketamine to albumin was developed and validated according to ICH Q2 (R1) guideline.
The stability of ketamine was also investigated because a yellowish discoloration of an aqueous solution of ketamine developed under heat. XRPD investigations showed the same crystal structure for all batches examined. An untargeted screening using LC HRMS as well as LC UV measurements showed no degradation of ketamine or the presence of impurities in stress and non-stressed ketamine solutions, confirming the stability of ketamine under the stress conditions investigated. The lower the quality of the water used in the stress tests, the more intense the yellow discoloration occurred. The impurity or the mechanism that causes the yellow discoloration could not be identified.
This thesis provides an edition and commentary of a manuscript discovered by Michael Stolberg in the archives of the central library in Zurich under the title “Mon aprendisage à l'Hôtel Dieu de Paris 1704.” (My apprenticeship at the Hôtel-Dieu de Paris 1704). The manuscript contains records of a midwifery student at the Hôtel-Dieu de Paris, an old hospital famous among others for its education in midwifery in the maternity ward. We read about managing different births, recipes for common remedies, direct questions answered by the maîtresse sage-femme, the leading midwife at the Hôtel-Dieu de Paris and more.
Although other accounts exist of the maternity ward at the Hôtel-Dieu de Paris, \(Mon\) \(Aprendisage\) is the first and only account from a midwife’s perspective that gives more than just instructions on obstetrical techniques. It takes us into the day-to-day experience of a woman as she progressed through her training at the Hôtel-Dieu.
Plexus injury often occurs after motor vehicle accidents and results in lifelong disability with severe neuropathic pain. Surgical treatment can partially restore motor functions, but sensory loss and neuropathic pain persist. Regenerative medicine concepts, such as cell replacement therapies for restoring dorsal root ganglia (DRG) function, set high expectations. However, up to now, it is unclear which DRG cell types are affected by nerve injury and can be targeted in regenerative medicine approaches.
This study followed the hypothesis that satellite glial cells (SGCs) might be a suitable endogenous cell source for regenerative medicine concepts in the DRG. SGCs originate from the same neural crest-derived cell lineage as sensory neurons, making them attractive for neural repair strategies in the peripheral nervous system. Our hypothesis was investigated on three levels of experimentation. First, we asked whether adult SGCs have the potential of sensory neuron precursors and can be reprogrammed into sensory neurons in vitro. We found that adult mouse DRG harbor SGC-like cells that can still dedifferentiate into progenitor-like cells. Surprisingly, expression of the early developmental transcription factors Neurog1 and Neurog2 was sufficient to induce neuronal and glial cell phenotypes. In the presence of nerve growth factor, induced neurons developed a nociceptor-like phenotype expressing functional nociceptor markers, such as the ion channels TrpA1, TrpV1 and NaV1.9. In a second set of experiments, we used a rat model for peripheral nerve injury to look for changes in the DRG cell composition. Using an unbiased deep learning-based approach for cell analysis, we found that cellular plasticity responses after nerve injury activate SGCs in the whole DRG. However, neither injury-induced neuronal death nor gliosis was observed. Finally, we asked whether a severe nerve injury changed the cell composition in the human DRG. For this, a cohort of 13 patients with brachial plexus injury was investigated. Surprisingly, in about half of all patients, the injury-affected DRG showed no characteristic DRG tissue. The complete entity of neurons, satellite cells, and axons was lost and fully replaced by mesodermal/connective tissue. In the other half of the patients, the basic cellular entity of the DRG was well preserved. Objective deep learning-based analysis of large-scale bioimages of the “intact” DRG showed no loss of neurons and no signs of gliosis.
This study suggests that concepts for regenerative medicine for restoring DRG function need at least two translational research directions: reafferentation of existing DRG units or full replacement of the entire multicellular DRG structure. For DRG replacement, SGCs of the adult DRG are an attractive endogenous cell source, as the multicellular DRG units could possibly be rebuilt by transdifferentiating neural crest-derived sensory progenitor cells into peripheral sensory neurons and glial cells using Neurog1 and Neurog2.
Clostridioides difficile is a bacterial species well known for its ability to cause C. difficile
infection (also known as CDI). The investigation of the role of this species in the human
gut has been so far dominated by a disease-centred perspective, focused on studying
C. difficile in relation to its associated disease.
In this context, the first aim of this thesis was to combine publicly available
metagenomic data to analyse the microbial composition of stool samples from patients
diagnosed with CDI, with a particular focus on identifying a CDI-specific microbial
signature.
However, similarly to many other bacterial species inhabiting the human gut, C.
difficile association with disease is not valid in absolute terms, as C. difficile can be
found also among healthy subjects. Further aims of this thesis were to 1) identify
potential C. difficile reservoirs by screening a wide range of habitats, hosts, body sites
and age groups, and characterize the biotic context associated with C. difficile
presence, and 2) investigate C. difficile within-species diversity and its toxigenic
potential across different age groups.
The first part of the thesis starts with the description of the concepts and
definitions used to identify bacterial species and within-species diversity, and then
proceeds to provide an overview of the bacterial species at the centre of my
investigation, C. difficile. The first Chapter includes a detailed description of the
discovery, biology and physiology of this clinically relevant species, followed by an
overview of the diagnostic protocols used in the clinical setting to diagnose CDI.
The second part of the thesis describes the methodology used to investigate
the questions mentioned above, while the third part presents the results of such
investigative effort. I first show that C. difficile could be found in only a fraction of the
CDI samples and that simultaneous colonization of multiple enteropathogenic species
able to cause CDI-like clinical manifestations is more common than previously
thought, raising concerns about CDI overdiagnosis. I then show that the CDIassociated
gut microbiome is characterized by a specific microbial signature,
distinguishable from the community composition associated with non-CDI diarrhea.
Beyond the nosocomial and CDI context, I show that while rarely found in adults, C.
difficile is a common member of the infant gut microbiome, where its presence is
associated with multiple indicators typical of a desirable healthy microbiome
development.
In addition, I describe C. difficile extensive carriage among asymptomatic
subjects, of all age groups and a potentially novel clade of C. difficile identified
exclusively among infants.
Finally, I discuss the limitations, challenges and future perspectives of my
investigation.