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The limited sensitivity of circulating tumor cell (CTC) detection in pancreatic adenocarcinoma (PDAC) stems from their extremely low concentration in the whole circulating blood, necessitating enhanced detection methodologies. This study sought to amplify assay-sensitivity by employing diagnostic leukapheresis (DLA) to screen large blood volumes. Sixty patients were subjected to DLA, with a median processed blood volume of ~ 2.8 L and approximately 5% of the resulting DLA-product analyzed using CellSearch (CS). Notably, DLA significantly increased CS-CTC detection to 44% in M0-patients and 74% in M1-patients, yielding a 60-fold increase in CS-CTC enumeration. DLA also provided sufficient CS-CTCs for genomic profiling, thereby delivering additional genomic information compared to tissue biopsy samples. DLA CS-CTCs exhibited a pronounced negative prognostic impact on overall survival (OS), evidenced by a reduction in OS from 28.6 to 8.5 months (univariate: p = 0.002; multivariable: p = 0.043). Additionally, a marked enhancement in sensitivity was achieved (by around 3-4-times) compared to peripheral blood (PB) samples, with positive predictive values for OS being preserved at around 90%. Prognostic relevance of CS-CTCs in PDAC was further validated in PB-samples from 228 PDAC patients, consolidating the established association between CTC-presence and reduced OS (8.5 vs. 19.0 months, p < 0.001). In conclusion, DLA-derived CS-CTCs may serve as a viable tool for identifying high-risk PDAC-patients and aiding the optimization of multimodal treatment strategies. Moreover, DLA enables comprehensive diagnostic profiling by providing ample CTC material, reinforcing its utility as a reliable liquid-biopsy approach. This high-volume liquid-biopsy strategy presents a potential pathway for enhancing clinical management in this malignancy.

Zusammenfssung Wir beschreiben Möglichkeiten auf dem Gebiet der molekularen Artidentifizierung sowie den Nutzen einer differenziellen Genexpression zur Altersbestimmung von Puppen und des Diapausestatus von Larven forensisch relevanter Schmeißfliegenarten.

Background Even though the COVID-19 vaccination roll-out in general can be considered as one of the most successful public health campaigns in the history of medicine, general vaccination hesitancy has remained an issue of concern throughout the world. We add to a deeper understanding of vaccination hesitancy by identifying what drives primary vaccination and booster uptake, as well as adherence to simple preventive measures such as physical distancing by investigating the role of Dark Triad personality traits, i.e. Machiavellianism, narcissism, and psychopathy. Methods We investigate data from Germany and the United Kingdom from the European Covid Survey which was collected from 23 December 2021 to 10 January 2022. Logit regressions and random effects regressions were performed to study the effect of dark personality traits on COVID-19-related prevention. Results We find a statistically significant association between Dark Triad personality traits and prevention efforts, primary vaccinations, and booster uptake against COVID-19. Specifically, individuals scoring high in psychopathy are associated with a lower likelihood of having received primary immunization. The marginal effect amounts to 3.31%-points. High narcissistic personality traits are correlated with a substantially higher likelihood (4.52%-points) to refuse booster shots after having received the primary vaccinations. Dark Triad personality traits may be relevant factors associated with vaccine-related decision-making. In addition, individuals with higher psychopathic tendencies report significantly lower engagement in other simple preventive behavior, while higher scores in narcissism are associated with higher reported adherence to simple preventive measures. Conclusions Our findings highlight the crucial role that personality plays in pandemic-related prevention. Policymakers, health professionals, and those in charge of health messaging may take these factors into account when devising communication strategies to improve the vaccination uptake and adherence to preventive behaviors. Future pandemics and public health crises would benefit from targeted, nuanced approaches to public health messaging to promote greater public adherence and public health.

Expression of all Yersinia pathogenicity factors encoded on the virulence plasmid, including the yop effector and the ysc type III secretion genes, is controlled by the transcriptional activator LcrF in response to temperature. Here, we show that a protein- and RNA-dependent hierarchy of thermosensors induce LcrF synthesis at body temperature. Thermally regulated transcription of lcrF is modest and mediated by the thermo-sensitive modulator YmoA, which represses transcription from a single promoter located far upstream of the yscW-lcrF operon at moderate temperatures. The transcriptional response is complemented by a second layer of temperature-control induced by a unique cis-acting RNA element located within the intergenic region of the yscW-lcrF transcript. Structure probing demonstrated that this region forms a secondary structure composed of two stemloops at 25°C. The second hairpin sequesters the lcrF ribosomal binding site by a stretch of four uracils. Opening of this structure was favored at 37°C and permitted ribosome binding at host body temperature. Our study further provides experimental evidence for the biological relevance of an RNA thermometer in an animal model. Following oral infections in mice, we found that two different Y. pseudotuberculosis patient isolates expressing a stabilized thermometer variant were strongly reduced in their ability to disseminate into the Peyer's patches, liver and spleen and have fully lost their lethality. Intriguingly, Yersinia strains with a destabilized version of the thermosensor were attenuated or exhibited a similar, but not a higher mortality. This illustrates that the RNA thermometer is the decisive control element providing just the appropriate amounts of LcrF protein for optimal infection efficiency.

Academic language is frequently assumed to be especially challenging for students from families of low socioeconomic status (SES) and even more so for language-minority students. Due to their often especially disadvantaged position regarding socioeconomic background and exposure to the language of instruction, language minority students are considered to suffer from a double disadvantage when processing complex academic language. To test this assumption, the present study investigated the relationships between various academic language features and differential item functioning (DIF) in a reading comprehension test for language-minority students on the one hand and German monolingual students from low-SES families on the other hand. The analyses are based on data of 19,108 fourth-grade students who took part in the reading comprehension test of the German National Assessment Study in elementary school. Our findings indicate that both lexical and grammatical features of academic language correlate with DIF disfavoring language-minority students, with especially pronounced effects for long and complex words and average sentence length. For German monolingual students from low-SES families, fewer features were associated with DIF, and the correlations were generally smaller than for language-minority students. Findings are discussed in relation to the assumed double disadvantage of language-minority students in the comprehension of academic language.

Colonization of the intestinal tract and dissemination into deeper tissues by the enteric pathogen Yersinia pseudotuberculosis demands expression of a special set of virulence factors important for the initiation and the persistence of the infection. In this study we demonstrate that many virulence-associated functions are coregulated with the carbohydrate metabolism. This link is mediated by the carbon storage regulator (Csr) system, including the regulatory RNAs CsrB and CsrC, and the cAMP receptor protein (Crp), which both control virulence gene expression in response to the nutrient composition of the medium. Here, we show that Crp regulates the synthesis of both Csr RNAs in an opposite manner. A loss of the crp gene resulted in a strong upregulation of CsrB synthesis, whereas CsrC levels were strongly reduced leading to downregulation of the virulence regulator RovA. Switching of the Csr RNA involves Crp-mediated repression of the response regulator UvrY which activates csrB transcription. To elucidate the regulatory links between virulence and carbon metabolism, we performed comparative metabolome, transcriptome, and phenotypic microarray analyses and found that Crp promotes oxidative catabolism of many different carbon sources, whereas fermentative patterns of metabolism are favored when crp is deleted. Mouse infection experiments further demonstrated that Crp is pivotal for a successful Y. pseudotuberculosis infection. In summary, placement of the Csr system and important virulence factors under control of Crp enables this pathogen to link its nutritional status to virulence in order to optimize biological fitness and infection efficiency through the infectious life cycle.

Commercial praline shells made from dark chocolate were filled with a mixture of invert sugar syrup, wine distillate and sucrose, which was adjusted to a viscosity of approximately 4 Pa·s by addition of pregelatinized starch. The pralines which also contained malt extract were subjected to storage at 20 and 24 °C. The liquefaction rate induced by enzymes of the malt extract depended on ethanol (0–15% w/w) and moisture content (approximately 30%) of the filling, and on storage temperature. The decay of apparent viscosity immediately after adding malt extract was delayed when ethanol was present in the filling, implying that viscosity stability after mixing and during subsequent processing is improved. Softening of the praline shells and fat bloom formation also depended on the ethanol concentration of the filling. A cross-comparison with praline shells which were filled with pure invert sugar syrup implies that the enzymes of the malt extract do not exhibit a negative influence on praline shell firmness. Electron micrographs give evidence that ethanol in contact with chocolate causes structural damage which results in a partial solubilization of praline shells.

The Sandfish (Scincidae: Scincus Scincus) Is a Lizard Capable of Moving through Desert Sand in a Swimming-Like Fashion. the Epidermis of this Lizard Shows a High Resistance against Abrasion Together with a Low Friction to Sand as an Adaption to a Subterranean Life below the Desert's Surface, Outperforming even Steel. the Low Friction Is Mainly Caused by Chemical Composition of the Scales, which Consist of Glycosylated β-Keratins. in this Study, the Friction, the Micro-Structure, the Glycosylation of the β-Keratin Proteins and β-Keratin Coding DNA of the Sandfish in Comparison to other Reptilian Species Was Investigated, Mainly with the Closely Related Berber Skink (Scincidae: Eumeces Schneideri) and another Sand Swimming Species, the Not Closer Related Shovel-Snouted Lizard (Lacertidae: Meroles Anchietae). Glycosylated β-Keratins of the Sandfish, Visualized with Different Lectins Resulted in O-Linked Glycans through PNA Employed as Carbohydrate Marker. Furthermore, the Glycosylation of β-Keratins in Various Squamatean Species Was Investigated and All Species Tested Were Found Positive; however, it Seems Like both Sand Swimming Species Examined Have a much Stronger Glycosylation of their β-Keratins. in Order to Prove this Finding through a Genetic Foundation, DNA of a β-Keratin Coding Gene of the Sandfish Was Sequenced and Compared with a Homologue Gene of Eumeces Schneideri. by Comparison of the Protein Sequence, a Higher Abundance of O-Glycosylation Sites Was Found in the Sandfish (enabled through the Amino Acids Serine and Threonine), Giving Molecular Support for a Higher Glycosylation of the β-Keratins in this Species.

Language competencies are crucial for success in the German educational system. The findings from the IQB-Ländervergleich 2011 (federal states comparison test of national educational standards) for elementary schools once again show that students from immigrant families are less proficient in German than their peers from native families. Special support for reading and second language acquisition is therefore needed. [PUBLICATION ABSTRACT]

The Sandfish (Scincidae: Scincus Scincus) Is a Lizard Capable of Moving through Desert Sand in a Swimming-Like Fashion. the Epidermis of this Lizard Shows a High Resistance against Abrasion Together with a Low Friction to Sand as an Adaption to a Subterranean Life below the Desert’s Surface, Outperforming even Steel. the Low Friction Is Mainly Caused by Chemical Composition of the Scales, which Consist of Glycosylated β-Keratins. in this Study, the Friction, the Micro-Structure, the Glycosylation of the β-Keratin Proteins and β-Keratin Coding DNA of the Sandfish in Comparison to other Reptilian Species Was Investigated, Mainly with the Closely Related Berber Skink (Scincidae: Eumeces Schneideri) and another Sand Swimming Species, the Not Closer Related Shovel-Snouted Lizard (Lacertidae: Meroles Anchietae). Glycosylated β-Keratins of the Sandfish, Visualized with Different Lectins Resulted in O-Linked Glycans through PNA Employed as Carbohydrate Marker. Furthermore, the Glycosylation of β-Keratins in Various Squamatean Species Was Investigated and All Species Tested Were Found Positive; however, it Seems Like both Sand Swimming Species Examined Have a much Stronger Glycosylation of their β-Keratins. in Order to Prove this Finding through a Genetic Foundation, DNA of a β-Keratin Coding Gene of the Sandfish Was Sequenced and Compared with a Homologue Gene of Eumeces Schneideri. by Comparison of the Protein Sequence, a Higher Abundance of O-Glycosylation Sites Was Found in the Sandfish (enabled through the Amino Acids Serine and Threonine), Giving Molecular Support for a Higher Glycosylation of the β-Keratins in this Species.