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- Frontiers in Psychology (2023) 14:1219915. https://doi.org/10.3389/fpsyg.2023.1219915 (1)
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- Redox Biology (2024) 70:103011. DOI: 10.1016/j.redox.2023.103011 (1)
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Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed.
Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated.
Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.).
Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.
The aim of the book is to ground the logical origins of consciousness in what I have previously called the ‘minimal self’. The idea is that elementary forms of consciousness are logically dependent not, as is commonly assumed, on ownership of an anatomical brain or nervous system, but on the intrinsic reflexivity that defines minimal selfhood. The book seeks to trace the logical pathway by which minimal selfhood gives rise to the possible appearance of consciousness. It is argued that in specific circumstances it thus makes sense to ascribe elementary consciousness to certain predatory single-celled organisms such as amoebae and dinoflagellates as well as to some of the simpler animals. Such an argument involves establishing exactly what those specific circumstances are and determining how elementary consciousness differs in nature and scope from its more complex manifestations.
The control of energy homeostasis is of pivotal importance for all living organisms. In the last years emerged the idea that many stress responses that are apparently unrelated, are actually united by a common increase of the cellular energy demand. Therefore, the so called energy signaling is activated by many kind of stresses and is responsible for the activation of the general stress response. In Arabidopsis thaliana the protein family SnF1- related protein kinases (SnRK1) is involved in the regulation of many physiological processes but is more known for its involvement in the regulation of the energy homeostasis in response to various stresses. To the SnRK1 protein family belong SnRK1.1 (also known as KIN10), SnRK1.2 (KIN11), and SnRK1.3 (KIN12). SnRK1 exerts its function regulating directly the activity of metabolic enzymes or those of key transcription factors (TFs). The only TFs regulated by SnRK1 identified so far is the basic leucine zipper (bZIP) 63. bZIP63 belongs to the C group of bZIPs (C-bZIPs) protein family together with bZIP9, bZIP10, and bZIP25. SnRK1.1 phosphorylates bZIP63 on three amino acids residues, serine (S) 29, S294, and S300. The phosphorylation of tbZIP63 is strongly related to the energy status of the plant, shifting from almost absent during the normal growth to strongly phosphorylated when the plant is exposed to extended dark. bZIPs normally bind the DNA as dimer in order to regulate the expression of their target genes. C-bZIPs preferentially form dimers with S1-bZIPs, constituting the so called C/S1- bZIPs network. The SnRk1 dependent phosphorylation of bZIP63 regulates its activation potential and its dimerization properties. In particular bZIP63 shift its dimerization preferences according to its phosphorylation status. The non-phosphorylated form of bZIP63 dimerize bZIP1, the phosphorylates ones, instead, forms dimer with bZIP1, bZIP11, and bZIP63 its self. Together with bZIP63, S1-bZIPs are important mediator of part of the huge transcriptional reprogramming induced by SnRK1 in response to extended dark. S1-bZIPs regulate, indeed, the expression of 4'000 of the 10'000 SnRK1-regulated genes in response to energy deprivation. In particular S1-bZIPs are very important for the regulation of many genes encoding for enzymes involved in the amino acid metabolism and for their use as alternative energy source. After the exposition for some hours to extended dark, indeed, the plant make use of every energy substrate and amino acids are considered an important energy source together with lipids and proteins. Interestingly, S1- bZIPs regulate the expression of ETFQO. ETFQO is a unique protein that convoglia the electrons provenienti from the branch chain amino acids catabolism into the mitochondrial electron transport chain. The dimer formed between bZIP63 and bZIP2 recruits SnRK1.1 directly on the chromatin of ETFQO promoter. The recruitment of SnRK1 on ETFQO promoter is associated with its acetylation on the lysine 14 of the histone protein 3 (K14H3). This chromatin modification is normally asociated with an euchromatic status of the DNA and therefore with its transcriptional activation. Beside the particular case of the regulation of ETFQO gene, S1-bZIPs are involved in the regulation of many other genes activated in response of different stresses. bZIP1 is for example an important mediator of the salt stress response. In particular bZIP1 regulates the primary C- and N-metabolism. The expression of bZIP1, in response of both salt ans energy stress seems to be regulated by SnRK1, as it is the expression of bZIP53 and bZIP63.
Beside its involvement in the regulation of the energy stress response and salt response, SnRK1 is the primary activators of the lipids metabolism during see germination. SnRK1, indeed, controls the expression of CALEOSINs and OLEOSINs. Those proteins are very important for lipids remobilization from oil droplets. Without their expression seed germination and subsequent establishment do not take place because of the absence of fuel to sustain these highly energy costly processes, which entirely depend on the catabolism of seed storages.
Plant-associated fungi can affect the plants‘ interaction with herbivores and
other microorganisms. For example, many common forage grasses are infected
with Epichloë endophytes. The endophytes systemically colonize the aerial
parts of the plants. They produce bioprotective alkaloids that can negatively
affect insects and livestock feeding on the grasses, and interact with other
fungal species which living from the plants‘ nutrients. Environmental conditions
strongly influence Epichloë endophytes. Endophyte-mediated effects
on herbivores are more pronounced under increased temperatures and the
endophytes may benefit from land use in managed grasslands. Under the
framework of the large-scale German project “Biodiversity Exploratories”, I
investigated whether infection rates and alkaloid concentrations of Epichloë
festucae var. lolii in Lolium perenne (Chapter I) and Epichloë endophytes (E.
uncinata, E. siegelii) in Festuca pratensis (Chapter II) depend on land use and
season. Further I analysed, whether foliar fungal assemblages of L. perenne
are affected by the presence of Epichloë endophytes (Chapter IV).
Almost once a week broadcasts about earthquakes, hurricanes, tsunamis, or forest fires are filling the news. While oneself feels it is hard to watch such news, it is even harder for rescue troops to enter such areas. They need some skills to get a quick overview of the devastated area and find victims. Time is ticking, since the chance for survival shrinks the longer it takes till help is available. To coordinate the teams efficiently, all information needs to be collected at the command center. Therefore, teams investigate the destroyed houses and hollow spaces for victims. Doing so, they never can be sure that the building will not fully collapse while they
are inside. Here, rescue robots are welcome helpers, as they are replaceable and make work more secure. Unfortunately, rescue robots are not usable off-the-shelf, yet.
There is no doubt, that such a robot has to fulfil essential requirements to successfully accomplish a rescue mission. Apart from the mechanical requirements it has to be able to build
a 3D map of the environment. This is essential to navigate through rough terrain and fulfil manipulation tasks (e.g. open doors). To build a map and gather environmental information, robots are equipped with multiple sensors. Since laser scanners produce precise measurements and support a wide scanning range, they are common visual sensors utilized for mapping.
Unfortunately, they produce erroneous measurements when scanning transparent (e.g. glass, transparent plastic) or specular reflective objects (e.g. mirror, shiny metal). It is understood that such objects can be everywhere and a pre-manipulation to prevent their influences is impossible. Using additional sensors also bear risks.
The problem is that these objects are occasionally visible, based on the incident angle of the laser beam, the surface, and the type of object. Hence, for transparent objects, measurements might result from the object surface or objects behind it. For specular reflective objects, measurements might result from the object surface or a mirrored object. These mirrored objects are illustrated behind the surface which is wrong. To obtain a precise map, the surfaces need to
be recognised and mapped reliably. Otherwise, the robot navigates into it and crashes. Further, points behind the surface should be identified and treated based on the object type. Points behind a transparent surface should remain as they represent real objects. In contrast, Points behind a specular reflective surface should be erased. To do so, the object type needs to be classified. Unfortunately, none of the current approaches is capable to fulfil these requirements.
Therefore, the following thesis addresses this problem to detect transparent and specular reflective objects and to identify their influences. To give the reader a start up, the first chapters
describe: the theoretical background concerning propagation of light; sensor systems applied for range measurements; mapping approaches used in this work; and the state-of-the-art concerning detection and identification of transparent and specular reflective objects. Afterwards, the Reflection-Identification-Approach, which is the core of subject thesis is presented. It describes 2D and a 3D implementation to detect and classify such objects. Both are available as ROS-nodes. In the next chapter, various experiments demonstrate the applicability and reliability of these nodes. It proves that transparent and specular reflective objects can be detected and classified. Therefore, a Pre- and Post-Filter module is required in 2D. In 3D, classification is possible solely with the Pre-Filter. This is due to the higher amount of measurements. An
example shows that an updatable mapping module allows the robot navigation to rely on refined maps. Otherwise, two individual maps are build which require a fusion afterwards. Finally, the
last chapter summarizes the results and proposes suggestions for future work.
Various research works and practitioners conclude that media pedagogy should be integrated in teacher education in order to enable future teachers to use media for their lessons effectively and successfully. However, this realization is not necessarily reflected in actual university curricula, as preservice teachers at some places can still finish their studies without ever dealing with media pedagogical issues. To understand, assess and eventually improve the status of media pedagogical teacher education, comprehensive research is required. Against this background, the following article seeks to present a theory-based and empirical overview of the status quo of preservice teachers’ pedagogical media competencies focusing Germany and the USA exemplarily. To form a basis, different models of pedagogical media competencies from both countries will be introduced and the extent to which these competencies have become part of teacher education programs and related studies will be summarised. Afterwards, method and selected results of a study will be described where the skills in question were measured with students from both countries, based on a comprehensive model of pedagogical media competencies that connects German and international research in this field. The international comparative perspective will help broaden the viewpoint and understand differences, but also similarities. These data serve to identify different ways of integrating media pedagogy into teacher training and draw conclusions on the consequences these processes entail for preservice teachers and their pedagogical media competencies.
Background
Epigenetic modifications may play a relevant role in the pathogenesis of human abdominal aortic aneurysm (AAA). The aim of the study was therefore to investigate histone acetylation and expression of corresponding lysine [K] histone acetyltransferases (KATs) in AAA.
Results
A comparative study of AAA tissue samples (n = 37, open surgical intervention) and healthy aortae (n = 12, trauma surgery) was performed using quantitative PCR, immunohistochemistry (IHC), and Western blot. Expression of the KAT families GNAT (KAT2A, KAT2B), p300/CBP (KAT3A, KAT3B), and MYST (KAT5, KAT6A, KAT6B, KAT7, KAT8) was significantly higher in AAA than in controls (P ≤ 0.019). Highest expression was observed for KAT2B, KAT3A, KAT3B, and KAT6B (P ≤ 0.007). Expression of KAT2B significantly correlated with KAT3A, KAT3B, and KAT6B (r = 0.705, 0.564, and 0.528, respectively, P < 0.001), and KAT6B with KAT3A, KAT3B, and KAT6A (r = 0.407, 0.500, and 0.531, respectively, P < 0.05). Localization of highly expressed KAT2B, KAT3B, and KAT6B was further characterized by immunostaining. Significant correlations were observed between KAT2B with endothelial cells (ECs) (r = 0.486, P < 0.01), KAT3B with T cells and macrophages, (r = 0.421 and r = 0.351, respectively, P < 0.05), KAT6A with intramural ECs (r = 0.541, P < 0.001) and with a contractile phenotype of smooth muscle cells (SMCs) (r = 0.425, P < 0.01), and KAT6B with T cells (r = 0.553, P < 0.001). Furthermore, KAT2B was associated with AAA diameter (r = 0.382, P < 0.05), and KAT3B, KAT6A, and KAT6B correlated negatively with blood urea nitrogen (r = −0.403, −0.408, −0.478, P < 0.05). In addtion, acetylation of the histone substrates H3K9, H3K18 and H3K14 was increased in AAA compared to control aortae.
Conclusions
Our results demonstrate that aberrant epigenetic modifications such as changes in the expression of KATs and acetylation of corresponding histones are present in AAA. These findings may provide new insight in the pathomechanism of AAA.
Perylene bisimide hydrogels and lyotropic liquid crystals with temperature-responsive color change
(2016)
The self-assembly of perylene bisimide (PBI) dyes bearing oligo ethylene glycol (OEG) units in water affords responsive functional nanostructures characterized by their lower critical solution temperature (LCST). Tuning of the LCST is realized by a supramolecular approach that relies on two structurally closely related PBI–OEG molecules. The two PBIs socially co-assemble in water and the resulting nanostructures exhibit a single LCST in between the transition temperatures of the aggregates formed by single components. This permits to precisely tune the transition from a hydrogel to a lyotropic liquid crystal state at temperatures between 26 and 51 °C by adjusting the molar fraction of the two PBIs. Owing to concomitant changes in PBI–PBI interactions this phase transition affords a pronounced color change with “fluorescence-on” response that can be utilized as a smart temperature sensory system.
The formation of macromolecular complexes within the crowded environment of cells often requires aid from assembly chaperones. PRMT5 and SMN complexes mediate this task for the assembly of the common core of pre-mRNA processing small nuclear ribonucleoprotein particles (snRNPs). Core formation is initiated by the PRMT5-complex subunit pICln, which pre-arranges the core proteins into spatial positions occupied in the assembled snRNP. The SMN complex then accepts these pICln-bound proteins and unites them with small nuclear RNA (snRNA). Here, we have analyzed how newly synthesized snRNP proteins are channeled into the assembly pathway to evade mis-assembly. We show that they initially remain bound to the ribosome near the polypeptide exit tunnel and dissociate upon association with pICln. Coincident with its release activity, pICln ensures the formation of cognate heterooligomers and their chaperoned guidance into the assembly pathway. Our study identifies the ribosomal quality control hub as a site where chaperone-mediated assembly of macromolecular complexes can be initiated.