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Beckmann, J.

Publications and source records attributed to Beckmann, J..

9 recordsLinked to original sources

InterScale reveals multi-scale cellular interaction programs in spatial transcriptomics

Tissue homeostasis and disease emerge from cell-cell interactions operating across spatial scales: from autocrine and juxtacrine signals within micrometers to paracrine gradients coordinating responses across tissues. While these can be read out from spatial transcriptomics, existing computational methods capture either local adjacency-based or long-range dependencies, but rarely both within a single framework. We introduce InterScale, a graph-transformer approach that jointly models local and global cellular interactions from spatial transcriptomics data. By integrating a Graph Convolutional Network as a local component with a global transformer encoder, InterScale learns multi-scale representations of cellular communication. A downstream workflow enables scale-resolved interpretation of interactions from gene to tissue level. Applied to Sonic Hedgehog morphogen patterning in neural organoids, InterScale resolves spatially restricted neuronal differentiation programs and broader progenitor regulatory states along the morphogen gradient. In a human pancreatic dataset contrasting healthy and type 1 diabetic tissue, it reveals disease-associated spatial reorganization and tissue remodeling. InterScales modular architecture supports diverse spatial transcriptomics platforms and provides a scalable, unbiased, and biologically interpretable framework for studying cellular interactions across scales.

bioinformatics↗

Virome of Culex nigripalpus at an Alabama aquaculture site reveals diverse insect-specific viruses and the impact of dual bioinformatic pipelines

Mosquitoes are important cosmopolitan insect vectors that threaten humans and host a variety of diseases. Catfish production from Alabama fisheries supports the development of favorable habitats that benefit fish, birds, and insects. Our study found that Culex nigripalpus was a major vector associated with catfish ponds. As Culex nigripalpus harbors medically important viruses like St. Louis encephalitis, studies often focus on these without exploring the full virus diversity. To address this, we performed an RNA-Seq analysis on Culex nigripalpus and compared bioinformatic methodologies, testing two approaches. In the first method (reference-based assembly), the characterized genome of Culex quinquefasciatus was used with a mapping cutoff, and assembled contigs were annotated with megablast against the NCBI nucleotide database. In a second method, reads were assembled de novo, and the contigs were annotated with a BLAST against the NCBI viral genomic database. In addition, the cross-validation of the contigs generated by the two methods was conducted to identify the common and unique viral contigs, adding support for identification. RNA-Seq analysis identified fifteen different viruses. Both methods identified three common viruses, Merida virus isolate Cx. nigripalpus1 (PQ963471), Hubei mosquito virus 5 isolate Cx. nigripalpus2 (PQ963472), and Zhejiang mosquito virus isolate Cx. nigripalpus3 (PQ963484). The first method also identified ten unique viruses, and the second method generated two unique viruses. Selected viruses were independently validated by RT-PCR amplification of viral genomic regions. Overall, our data suggest that different approaches to bioinformatic analysis complement each other and improve viral genome recovery from metatranscriptomic datasets.

microbiology↗

Patterns of sleeping site use of Guinea baboon parties (Papio papio)

Sleeping site use in primates is thought to be influenced by multiple factors, including resource availability and competition, predation risk, and the risk of parasitic infection. While previous research has highlighted the importance of these factors, few studies have examined sleeping site use among multiple groups of non-territorial species with overlapping home ranges. Here, we investigated the sleeping site use of Guinea baboons (Papio papio) in Simenti, Senegal. We used locational data for four years of several baboon parties sharing the same range. We assessed the distribution of sleeping sites within the local habitat mosaic, the proximity of sleeping sites to those of co-occurring parties and the impact of food availability and predator presence at the landscape level on the distance between parties sleeping sites on the same night. We further investigated patterns of sleeping site use of parties across time. We found that the vast majority of sleeping sites were in the gallery forest along the perennial Gambia River, likely due to the availability of tall trees. Guinea baboons slept in close spatial proximity (>50m) to at least one other party regardless of food availability and predator presence. Patterns of sleeping site use showed no evidence of predator or parasite avoidance. Thus, Guinea baboons in Simenti likely use the abundantly available sleeping sites opportunistically rather than being driven by intergroup competition or strategies for predator avoidance or reduction of the risk of parasite infection.

ecology↗

Ocular Disease Prevalence in California Sea Lions In Human Care: Freshwater Versus Saltwater Housing

California sea lions (Zalophus californianus), are susceptible to various ocular diseases, with some literature suggesting a heightened risk for those kept in freshwater pools as opposed to saltwater. Given the potential implications of housing conditions on animal health, we wanted to analyze the ocular health of two distinct groups of sea lions kept at Nuremberg Zoo, one housed in freshwater and the other in saltwater. Data extracted from the animals medical records over a ten-year period were used to compare the incidence of eye conditions and other medical conditions observed. The results revealed no significant difference in the overall prevalence of eye diseases between the two environments. However, a distinct seasonal pattern was noted: sea lions kept in freshwater exhibited a peak in eye disorders during the summer months, while those in saltwater displayed a more uniform distribution of the occurrence of ocular diseases throughout the year. These findings suggest that sun exposure and water quality are potentially more influential factors in the development of ocular diseases in pinnipeds than salinity or UV radiation. Further studies are necessary to elucidate the underlying mechanisms and optimize care practices for these marine mammals. Simple SummaryThis study investigated the ocular health of California sea lions (Zalophus californianus) at Nuremberg Zoo, comparing those housed in freshwater pools to those in saltwater. An analysis of medical records over ten years showed no significant difference in the overall prevalence of eye diseases between the two groups. However, sea lions in freshwater experienced a peak of eye disorders in the summer, while those in saltwater had a more consistent occurrence throughout the year. These results imply that factors such as sun exposure and water quality may play a more crucial in ocular disease development than salinity or UV radiation. The study highlights the need for further research to understand these dynamics and improve care for marine mammals.

zoology↗

Patterns of landscape partitioning indicate low levels of resource competition among neighbouring Guinea baboon(Papio papio) parties

BackgroundAccess to critical resources, including food, water, or shelter, significantly determines individual fitness. As these resources are limited in most habitats, animals may employ strategies of landscape partitioning to mitigate the impact of direct resource competition. Territoriality may be regarded as an aggressive form of landscape partitioning but in non-territorial species, other forms exist. Animals living in groups with greater flexibility in their association patterns, such as multilevel societies with fission-fusion dynamics, may adjust their grouping and space use patterns to short-term variations in ecological conditions such as food availability, predation pressure, or the presence of conspecific groups. This flexibility may allow them to balance the costs of competition while reaping the benefits of better predator detection and defence. MethodsWe explored patterns of landscape partitioning among neighbouring Guinea baboon (Papio papio) parties in the Niokolo-Koba National Park, Senegal. Guinea baboons live in a multilevel society in which parties predictably form higher-level associations ("gangs"). We used four years of locational data from individuals equipped with GPS collars to estimate annual home ranges, home range overlap, and minimum distances between parties. We examined whether food availability and predator presence levels affected the cohesion between parties in 2022. ResultsWe found substantial home range and core area overlap among parties (33 to 100%). We found no effect of food availability or predator presence on the distance to the closest neighbouring party; the minimum distance between parties was less than 100 m on average. ConclusionsOur results suggest a low level of feeding competition between our study parties. Whether this is a general feature of Guinea baboons or particular to the situation in the Niokolo-Koba National Park remains to be investigated.

ecology↗

Increased female competition for males with enhanced foraging skills in Guinea baboons

Recognizing skillful group members is crucial for making optimal social choices. Whether and how nonhuman animals attribute skill to others is still debated. Using a lever-operated food box, we enhanced the foraging skill of a single male (the specialist) in one zoo housed and two wild groups of Guinea baboon (Papio papio). We measured group members behav-ioral responses before, during, and after our manipulation to reveal whether they focused on the outcome of the males actions or changed their assessment of his long-term value. During the manipulation, females in the specialists unit, but not the wider group, competed over ac-cess to the specialist - increasing their grooming of him tenfold and aggression near him four-fold. Both behaviors were predicted by the amount each female ate from the food box and re-turned to baseline within two weeks of its removal. This behavioral pattern supports an out-come-based assessment where females responded to male-provided benefits (utility) rather than attributing competence (value). TeaserGuinea baboon females monopolize males in relation to their current perceived utility.

animal behavior and cognition↗

Xylazine co-self-administration suppresses fentanyl consumption during self-administration and induces a unique sex-specific withdrawal syndrome that is not altered by naloxone in rats

Prescription and illicit opioid use are a public health crisis, with the landscape shifting to fentanyl use. Since fentanyl is 100-fold more potent than morphine, its use is associated with a higher risk of fatal overdose that can be remediated through naloxone (Narcan) administration. However, recent reports indicate that xylazine, an anesthetic, is increasingly detected in accidental fentanyl overdose deaths. Anecdotal reports suggest that xylazine may prolong the fentanyl "high", alter the onset of fentanyl withdrawal, and increase resistance to naloxone-induced reversal of overdose. To date no preclinical studies have evaluated the impacts of xylazine on fentanyl self-administration (SA; 2.5 g/kg/infusion) or withdrawal to our knowledge. We established a rat model of xylazine/fentanyl co-SA and withdrawal and evaluated outcomes as a function of biological sex. When administered alone, chronic xylazine (2.5 mg/kg, IP) induced unique sex-specific withdrawal symptomatology whereby females showed delayed onset of signs and a possible enhancement of sensitivity to the motor-suppressing effects of xylazine. Xylazine reduced fentanyl consumption both male and female rats regardless of whether it was experimenter-administered or added to the intravenous fentanyl product (0.05. 0.10, and 0.5 mg/kg/infusion) when compared to fentanyl SA alone. Interestingly, this effect was dose-dependent when self-administered intravenously. Naloxone (0.1 mg/kg, SC) did not increase somatic signs of fentanyl withdrawal, regardless of the inclusion of xylazine in the fentanyl infusion in either sex; however, somatic signs of withdrawal were higher across timepoints in females after xylazine/fentanyl co-SA regardless of naloxone exposure as compared to females following fentanyl SA alone. Together, these results indicate that xylazine/fentanyl co-SA dose-dependently suppressed fentanyl intake in both sexes, and induced a unique withdrawal syndrome in females which was not altered by acute naloxone treatment.

animal behavior and cognition↗

Primary Omicron infection elicits weak antibody response but robust cellularimmunity in children

Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We determined immune responses following Omicron BA.1/2 infection in children aged 6-14 years and related this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicited a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicited increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primed for robust antibody responses following Omicron infection but these remained primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses were robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown.

immunology↗

Genomic Analyses of SLAMF7 CAR-T Cells Manufactured by Sleeping Beauty Transposon Gene Transfer for Immunotherapy of Multiple Myeloma

Widespread treatment of human diseases with gene therapies necessitates the development of gene transfer vectors that integrate genetic information effectively, safely and economically. Accordingly, significant efforts have been devoted to engineer novel tools that i) achieve high-level stable gene transfer at low toxicity to the host cell; ii) induce low levels of genotoxicity and possess a safe integration profile with a high proportion of integrations into safe genomic locations; and iii) are associated with acceptable cost per treatment and scalable/exportable vector production to serve large numbers of patients. The Sleeping Beauty (SB) transposon has been transformed into a vector system that is fulfilling these requirements.\n\nIn the CARAMBA project, we use SB transposition to genetically modify T cells with a chimeric antigen receptor (CAR) specific for the SLAMF7 antigen, that is uniformly and highly expressed on malignant plasma cells in multiple myeloma. We have demonstrated that SLAMF7 CAR-T cells confer specific and very potent anti-myeloma reactivity in pre-clinical models, and are therefore preparing a Phase I/IIa clinical trial of adoptive immunotherapy with autologous, patient-derived SLAMF7-CAR T cells in multiple myeloma (EudraCT Nr. 2019-001264-30/CARAMBA-1).\n\nHere we report on the characterization of genomic safety attributes in SLAMF7 CAR-T cells that we prepared in three clinical-grade manufacturing campaigns under good manufacturing practice (GMP), using T cells that we obtained from three healthy donor volunteers. In the SLAMF7 CAR-T cell product, we determined the average transposon copy number, the genomic insertion profile, and presence of residual SB100X transposase. The data show that the SLAMF7 CAR transposon had been inserted into the T cell genome with the close-to-random distribution pattern that is typical for SB, and with an average transposon copy number ranging between 6 and 12 per T cell. No residual SB100X transposase could be detected by Western blotting in the infusion products. With these attributes, the SLAMF7 CAR-T products satisfy criteria set forth by competent regulatory authorities in order to justify administration of SLAMF7 CAR-T cells to humans in the context of a clinical trial. These data set the stage for the CARAMBA clinical trial, that will be the first in the European Union to use virus-free SB transposition for CAR-T engineering.\n\nDisclosuresThis project is receiving funding from the European Unions Horizon 2020 research and innovation programme under grant agreement No 754658 (CARAMBA).

bioengineering↗