Biology subjects

Jacobsen, J.

Publications and source records attributed to Jacobsen, J..

6 recordsLinked to original sources

bioRxiv2026

Layer-by-Layer Polymeric Films: A Novel Approach to Buccal GLP-1 Delivery

Buccal delivery offers a promising alternative to oral drug administration by enabling direct systemic absorption and avoiding first-pass metabolism. Multilayer polymeric films represent a promising strategy for the sequential delivery of drug and absorption enhancer in the oral cavity. Here, dual- and triple-layer films were fabricated via slot-die coating, incorporating a GLP-1 receptor agonist (GLP-1-RA) and the penetration enhancer sodium glycodeoxycholate (GDC). These were co-loaded in dual-layer films or compartmentalized in triple-layer films. Scanning electron microscopy and optical coherence tomography confirmed well-defined, distinct layers with thicknesses suitable for buccal administration (339 {+/-} 10.24 {micro}m and 487 {+/-} 36.5 {micro}m for dual- and triple-layer films, respectively). Both designs exhibited good mucoadhesion and mucosal compatibility, and preserved the secondary structure of GLP-1-RA. In vitro release studies showed rapid diffusion of GDC and GLP-1-RA from dual-layer films, whereas triple-layer films enabled sustained, sequential release of GDC and GLP-1-RA. Ex vivo porcine buccal mucosa studies showed higher GLP-1-RA and GDC flux from triple-layer films compared to dual-layer films. The films also did not compromise epithelial integrity, in contrast to the direct application of GLP-1-RA and GDC, which caused significant epithelial disruption. These results demonstrate that multilayer film architecture and spatial layering can be harnessed to control release kinetics, maximize peptide penetration, and minimize tissue stress, offering a versatile platform for safe and effective peptide delivery. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/700335v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@76858borg.highwire.dtl.DTLVardef@1397e74org.highwire.dtl.DTLVardef@19d1841org.highwire.dtl.DTLVardef@a369c5_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

The "value perspectives of nature" scale: A validated scale to measure plural value perspectives of future nature from a transformative angle.

Sustainability transformations critically depend on understanding, assessing and monitoring the plural values of nature held across societies. However, while conceptual frameworks increasingly acknowledge a plurality of values, empirical indicators to reliably assess these multiple value types and their sub-dimensions remain scarce. We introduce the Plural Values of Nature (PVN) scale, integrating intrinsic, instrumental, and relational values into one multi-dimensional scale. This psychometric scale consists of 11 items and is designed to capture both distinctiveness and overlap of values. Using a seven-step process that includes qualitative and cognitive interviews, expert evaluations, and quantitative pre-testing and validation the scale is refined and validated across five European countries (representative sample; n = 1028). The validation study shows moderate to high internal consistency, reliability, and validity of the scale across all countries. Based on the development and validation of the PVN, we discuss methodological and conceptual issues and unpack the plurality of values of nature. Initial results show that considering the plurality of values is important to understand peoples attitudes towards e.g., nature restoration: People that endorse multiple values show more positive attitudes towards nature restoration than people endorsing only one specific value type (either instrumental, intrinsic, or relational values), with people endorsing all three value types simultaneously showing the highest support for such policies. As a concise survey-based social indicator, the PVN scale can be used to take stock of the plural values that societies hold regarding the future development of nature and to monitor potential shifts over time.

scientific communication and education↗

bioRxiv2020

DreamAI: algorithm for the imputation of proteomics data

Deep proteomics profiling using labeled LC-MS/MS experiments has been proven to be powerful to study complex diseases. However, due to the dynamic nature of the discovery mass spectrometry, the generated data contain a substantial fraction of missing values. This poses great challenges for data analyses, as many tools, especially those for high dimensional data, cannot deal with missing values directly. To address this problem, the NCI-CPTAC Proteogenomics DREAM Challenge was carried out to develop effective imputation algorithms for labeled LC-MS/MS proteomics data through crowd learning. The final resulting algorithm, DreamAI, is based on an ensemble of six different imputation methods. The imputation accuracy of DreamAI, as measured by Pearson correlation, is about 15%-50% greater than existing tools among less abundant proteins, which are more vulnerable to be missed in proteomics data sets. This new tool notably enhances data analysis capabilities in proteomics research.

bioinformatics↗

bioRxiv2020

Multi-Omic Analysis Reveals Cannabidiol Disruption of Cholesterol Homeostasis in Human Cell Lines

The non-psychoactive cannabinoid, cannabidiol (CBD), is FDA-approved for treatment of two drug-resistant epileptic disorders, and is seeing increased use among the general public, yet the mechanisms that underlie its therapeutic effects and side-effect profiles remain unclear. Here, we report a systems-level analysis of CBD action in human cell lines using temporal multi-omic profiling. FRET-based biosensor screening revealed that CBD treatment resulted in a sharp rise in cytosolic calcium, and activation of AMPK and ERK kinases in human keratinocyte and neuroblastoma cell lines. CBD treatment led to alterations in the abundance of metabolites, mRNA transcripts, and proteins consistent with activation of cholesterol biosynthesis, transport and storage. We found that CBD rapidly incorporated into cellular membranes and altered cholesterol chemical activity, suggesting direct perturbation of cholesterol-dependent membrane properties. CBD treatment induced apoptosis in a dose-dependent manner in multiple human cell lines, which was rescued by inhibition of cholesterol synthesis, and potentiated by compounds that disrupt cholesterol trafficking and storage. Our data point to a pharmacological interaction of CBD with cholesterol homeostasis pathways, with potential implications in its therapeutic use.

systems biology↗

bioRxiv2019

Rapid discovery of drug target engagement by isothermal shift assay

Identifying protein targets directly bound by drug molecules within living systems remains challenging. Here we present the isothermal shift assay, iTSA, for rapid identification of drug targets. Compared with thermal proteome profiling, a prevailing method for target engagement, iTSA offers a simplified workflow, 4-fold higher throughput, and multiplexed experimental designs with higher replication. We demonstrate application of iTSA to identify targets for several kinase inhibitors in lysates and living cells.

pharmacology and toxicology↗

bioRxiv2016

The Monarch Initiative: Insights across species reveal human disease mechanisms

The principles of genetics apply across the whole tree of life: on a cellular level, we share mechanisms with species from which we diverged millions or even billions of years ago. We can exploit this common ancestry at the level of sequences, but also in terms of observable outcomes (phenotypes), to learn more about health and disease for humans and all other species. Applying the range of available knowledge to solve challenging disease problems requires unified data relating genomics, phenotypes, and disease; it also requires computational tools that leverage these multimodal data to inform interpretations by geneticists and to suggest experiments. However, the distribution and heterogeneity of databases is a major impediment: databases tend to focus either on a single data type across species, or on single species across data types. Although each database provides rich, high-quality information, no single one provides unified data that is comprehensive across species, biological scales, and data types. Without a big-picture view of the data, many questions in genetics are difficult or impossible to answer. The Monarch Initiative (https://monarchinitiative.org) is an international consortium dedicated to providing computational tools that leverage a computational representation of phenotypic data for genotype-phenotype analysis, genomic diagnostics, and precision medicine on the basis of a large-scale platform of multimodal data that is deeply integrated across species and covering broad areas of disease.

evolutionary biology↗