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Schulz, K.

Publications and source records attributed to Schulz, K..

7 recordsLinked to original sources

Buffaloed in Brandenburg: Germany's first Brush with Foot-and-Mouth Disease after four Decades of Freedom

Foot-and-mouth disease (FMD) virus is one of the most feared and most consequential pathogens of livestock worldwide. It can be spread rapidly by the transboundary movement of animals, animal products and byproducts. In January 2025, Germany detected its first FMD outbreak since 1988 in extensively reared water buffalo on a small farm in the state of Brandenburg, directly outside Berlin, the federal capital. Immediate control measures including a standstill for movements of susceptible animals and pre-emptive culling were implemented by the veterinary authorities. Whole-genome sequencing identified the virus as serotype O, topotype ME-SA, lineage SA-2018 and revealed extensive recombination, but cross-neutralization assays suggested good heterologous protection by an O/PanAsia-2 vaccine strain. Epidemiological back-calculation placed the time of virus introduction in late December 2024. Although the entry route remains unresolved, human-associated introduction is most likely. Network analysis revealed minimal farm connectivity, and simulations predicted low potential for onward transmission, which is consistent with the outbreak being ultimately restricted to a single herd. This event underscores the constant and unpredictable risk of introduction of the virus. Early detection through increased awareness and comprehensive differential diagnostics as well as the international collaboration of veterinary services, laboratories and experts are essential in the face of the global presence of FMD.

microbiology↗

Cell-type specific astrocyte activation is driven by cortical top-down modulation

Cortical projections to cortical and subcortical targets provide top-down modulation that shapes neuronal performance, including gain control and excitation-inhibition balance. However, the contribution of astrocytes to this process remains poorly understood. In the olfactory bulb, the first relay station of odor information processing, bottom-up input is transmitted from olfactory sensory neurons to mitral/tufted (M/T) cells, which project to the olfactory cortex. Context- and state-dependent top-down modulation arises from feedback projections originating in the anterior piriform cortex (aPC) that target granule cells (GCs). We examined how astrocytes respond to bottom-up and top-down neuronal activity using confocal Ca{superscript 2} imaging, cell-type-specific optogenetics, electrical stimulation, and single-cell electrophysiology. We found that Ca{superscript 2} signals in astrocytes are selectively triggered by action potential-dependent ATP release from GCs while M/T cells failed to elicit significant astrocytic responses. Although synaptic input from M/T cells depolarized GCs, it was insufficient to induce action potential firing and subsequent astrocyte activation. By contrast, glutamatergic top-down input from the aPC evoked sustained GC firing, leading to ATP-dependent Ca{superscript 2} signaling in astrocytes. Our results reveal an unappreciated level of complexity in neuron-astrocyte communication, highlighting its cell-type specificity as well as its context- and state-dependence.

neuroscience↗

Proteomic Remodeling During Tumor Cell-Induced Platelet Aggregation Unveils Metastatic Drivers in Colorectal Cancer

BackgroundColorectal cancer (CRC) is frequently associated with metastasis, resulting in high mortality rates. Platelets are known to play a crucial role in the metastatic cascade influencing tumor microenvironment remodeling, promoting cell transformation, facilitating metastatic niche formation, and shielding circulating tumor cells from immune surveillance. However, platelet proteomic alterations during tumor cell-induced platelet aggregation (TCIPA) remain largely unexplored. This study aims to characterize the proteomic profile of TCIPA in CRC using an in vitro model that recapitulates key aspects of CRC metastasis. MethodsTCIPA was assessed via light transmission aggregometry using an in vitro model incorporating paired primary and metastatic cell cultures. Stable Isotope Labeling with Amino Acids in Cell culture (SILAC) allowed for the discrimination of healthy platelet and tumor cell proteomes prior to and following TCIPA. Data-independent acquisition mass spectrometry was employed to analyze intra- and extracellular tumor and platelet proteomes. Comparative proteomic profiling was performed using a range of bioinformatic analyses, including clustering, differential expression, and Gene Set Enrichment Analyses (GSEA). ResultsComparison of the baseline proteome profiles of the CRC cell lines SW480 and SW620 identified 263 significant differentially expressed proteins (FDR [≤] 0.05, log2FC [≥] 1). The GSEA demonstrated enrichment of the epithelial-mesenchymal transition (FDR: 5.617 x 10-5) gene set in SW480 cells. While SW480 exhibited rapid TCIPA, SW620 did not consistently interact with healthy platelets. Following TCIPA, 34 tumor proteins showed differential expression compared to their naive status (without platelet-exposure). Notably, 17 of these proteins were significantly associated with CRC progression, particularly in the promotion of EMT, metastasis, tumor cell survival, proliferation, and metabolic reprogramming. ConclusionsThis study successfully characterized the proteomic profiles of platelets, platelet secretomes, and colorectal tumor cells following TCIPA-induced activation. The findings highlight the significant role of several tumor proteins and their metabolic effects in colorectal cancer progression, particularly with regard to metastasis.

cancer biology↗

Local selection shaped the diversity of European maize landraces

The introduction of populations to novel environments can lead to a loss of genetic diversity and the accumulation of deleterious mutations due to selection and demographic changes. We investigate how the recent introduction of maize to Europe shaped the genetic diversity and differentiation of European traditional maize populations and quantify the impact of its recent range expansion and consecutive breeding on the accumulation of genetic load. We use genome-wide genetic markers of almost 2,000 individuals from 38 landraces, 155 elite breeding lines and a large set of doubled haploid lines derived from two landraces to find extensive population structure within European maize, with landraces being highly differentiated even over short geographic distances. Yet, diversity change does not follow the continuous pattern of range expansions. Landraces maintain high genetic diversity that is distinct between populations and does not decrease along the possible expansion routes. Signals of positive selection in European landraces that overlap with selection in Asian maize suggest convergent selection during maize introductions. At the same time, environmental factors partially explain genetic differences across Europe. Consistent with the maintenance of high diversity, we find no evidence of genetic load accumulating along the maize introduction route in European maize. However, modern breeding likely purged highly deleterious alleles but accumulated genetic load in elite germplasm. Our results reconstruct the history of maize in Europe and show that landraces have maintained high genetic diversity that could reduce genetic load in the European maize breeding pools.

evolutionary biology↗

Microgliosis, astrogliosis and loss of aquaporin-4 polarity in frontal cortex of COVID-19 patients

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), causing human coronavirus disease 2019 (COVID-19), not only affects the respiratory tract, but also impacts other organs including the brain. A considerable number of COVID-19 patients develop neuropsychiatric symptoms that may linger for weeks and months and contribute to "long-COVID". While the neurological symptoms of COVID-19 are well described, the cellular mechanisms of neurologic disorders attributed to the infection are still enigmatic. Here, we studied the effect of an infection with SARS-CoV-2 on the structure and expression of marker proteins of astrocytes and microglial cells in the frontal cortex of patients who died from COVID-19 in comparison to non-COVID-19 controls. Most of COVID-19 patients had microglial cells with retracted processes and rounded and enlarged cell bodies in both gray and white matter, as visualized by anti-Iba1 staining and confocal fluorescence microscopy. In addition, gray matter astrocytes in COVID-19 patients were frequently labeled by intense anti-GFAP staining, whereas in non-COVID-19 controls, most gray matter astrocytes expressed little GFAP. The most striking difference between astrocytes in COVID-19 patients and controls was found by anti-aquaporin-4 (AQP4) staining. In COVID-19 patients, a large number of gray matter astrocytes showed an increase in AQP4. In addition, AQP4 polarity was lost and AQP4 covered the entire cell, including the cell body and all cell processes, while in controls, AQP4 immunostaining was mainly detected in endfeet around blood vessels and did not visualize the cell body. In summary, our data suggest neuroinflammation upon SARS-CoV-2 infection including microgliosis and astrogliosis, including loss of AQP4 polarity.

neuroscience↗

L-SCRaMbLE creates large-scale genome rearrangements in synthetic Sc2.0 chromosomes

Optimization of the metabolic flux through heterologous pathways to improve bioproduction or utilization of alternative substrates requires both fine-tuning of non-native gene expression levels and improvement of the host genome. The SCRaMbLE system incorporated into synthetic Sc2.0 yeast strains enables a rapid approach to rearrange the genome of Saccharomyces cerevisiae in order to create optimized chassis. Here, we show that the light-inducible Cre recombinase L-SCRaMbLE can efficiently generate diverse recombination events when applied to Sc2.0 strains containing a linear or circular synthetic chromosome III. We present an efficient and straightforward workflow for the identification of complex rearranged synthetic chromosomes from SCRaMbLEd isolates without selection pressure. The screening method is based on novel genotyping primers, the loxPsym tags, which indicate not only deletions but also inversions and translocations. Long-read Nanopore sequencing is used to decode the selected genotypes and shows in conjunction with flow cytometry that large-scale karyotype alterations can be a consequence of SCRaMbLE.

synthetic biology↗

The involvement of type IV pili and phytochrome in gliding motility, lateral motility and phototaxis of the cyanobacterium Phormidium lacuna

Phormidium lacuna, a filamentous cyanobacterium without heterocysts, can be transformed by natural transformation. These filaments are motile on agar and other surfaces and display rapid lateral movements in liquid culture. Furthermore, they exhibit phototactic response under vertical illumination in Petri dishes. We generated mutants in which a KanR resistance cassette was integrated in the phytochrome gene cphA and in various genes of the type IV pilin apparatus. pilM, pilN, pilQ and pilT mutants were defective in all three responses, indicating that type IV pili are involved in all three kinds of motility. Rapid movements of wild type in liquid culture requires an extracellular matrix with type IV pili as central player. pilB mutants are only partially blocked in their responses. pilB is the proposed ATPase for expelling of the filament. In the mutant, this function could be overtaken by an alternative protein, like pilT, which regularly mediates retraction of pili. The cphA mutant revealed a significantly reduced phototactic response towards red light. We assume that together with other photoreceptors, CphA regulates the phototactic response by down regulation of surface attachment.

microbiology↗