6 Citations
To ensure safe long-term use topical products should be investigated to understand how they interact with the resident skin microbiota to mitigate potential risk Sunscreens are essential for protecting skin from UV damage but their effects on skin-resident microbes have not been well characterized We examined the impact of two sunscreen formulations containing titanium dioxide or zinc oxide on both cultured skin bacteria and the skin microbiomes of human volunteers No loss of viability was observed after a h exposure to either sunscreen in cultures of Staphylococcus epidermidis Staphylococcus capitis Staphylococcus hominis Micrococcus luteus and Corynebacterium tuberculostearicum The effects of ... More
To ensure safe, long-term use, topical products should be investigated to understand how they interact with the resident skin microbiota to mitigate potential risk. Sunscreens are essential for protecting skin from UV damage, but their effects on skin-resident microbes have not been well characterized. We examined the impact of two sunscreen formulations (containing titanium dioxide or zinc oxide) on both cultured skin bacteria and the skin microbiomes of human volunteers. No loss of viability was observed after a 2 h exposure to either sunscreen in cultures of Staphylococcus epidermidis, Staphylococcus capitis, Staphylococcus hominis, Micrococcus luteus, and Corynebacterium tuberculostearicum. The effects of the sunscreens were then studied across the skin microbiomes of 20 human participants. Skin swabs were collected before application and at 1, 6, and 24 h afterward. DNA was extracted and sequenced at the 16S rRNA V4 region, and sequences were denoised and taxonomically assigned using the nf-core/ampliseq pipeline. Across all time points, alpha diversity (Shannon index, Friedman test) and beta diversity (permutational multivariate analysis of variance) remained stable, with no significant differences in beta dispersion. Differential abundance analysis revealed minor fluctuations in some low-abundance genera, identified as likely transient due to their low prevalence, but overall resident community composition was not significantly altered. These findings suggest that short-term sunscreen application does not disrupt the skin microbiome, supporting their safe use from a microbial standpoint. Outcomes from both in vitro and in vivo experimentation point to the compositional resilience of the skin microbiota to sunscreens. Less
Physical activity improves health yet the molecular mechanisms remain partially understood This study presents a high-resolution time-resolved atlas profiling proteins across plasma saliva and urine from healthy adults post-acute exercise Exercise regulated over proteins revealing distinct fluid-specific temporal dynamics By integrating fluid-specific exercise signatures with tissue and disease atlases we delineated the contribution of tissues and associations to various diseases Network analysis across body fluids elucidated coordinated remodeling in the extracellular matrix and immune activation orchestrating exercise-induced networks Many exercise-responsive plasma proteins were robust across age sex and exercise modalities indicating a conserved systemic signature Integration with genetic data established ... More
Physical activity improves health, yet the molecular mechanisms remain partially understood.
This study presents a high-resolution, time-resolved atlas profiling 10,127 proteins across
plasma, saliva, and urine from healthy adults post-acute exercise. Exercise regulated over
3,000 proteins, revealing distinct, fluid-specific temporal dynamics. By integrating fluid-specific
exercise signatures with tissue and disease atlases, we delineated the contribution of tissues
and associations to various diseases. Network analysis across body fluids elucidated
coordinated remodeling in the extracellular matrix and immune activation orchestrating
exercise-induced networks. Many exercise-responsive plasma proteins were robust across
age, sex, and exercise modalities, indicating a conserved systemic signature. Integration with
genetic data established exercise-regulated proteins as modulators of metabolic traits and
identified over 200 targeted by approved drugs, highlighting their impact on disease-relevant
pathways. This comprehensive atlas, available as an open-access resource
https://cbmr.ku.dk/research/research-groups/deshmukh-group/shiny-apps/, advances our
molecular insight into exercise adaptations and enables exerkine discovery, biomarker
development, and pharmacological exercise-mimetic strategies. Less
This study presents a high-resolution, time-resolved atlas profiling 10,127 proteins across
plasma, saliva, and urine from healthy adults post-acute exercise. Exercise regulated over
3,000 proteins, revealing distinct, fluid-specific temporal dynamics. By integrating fluid-specific
exercise signatures with tissue and disease atlases, we delineated the contribution of tissues
and associations to various diseases. Network analysis across body fluids elucidated
coordinated remodeling in the extracellular matrix and immune activation orchestrating
exercise-induced networks. Many exercise-responsive plasma proteins were robust across
age, sex, and exercise modalities, indicating a conserved systemic signature. Integration with
genetic data established exercise-regulated proteins as modulators of metabolic traits and
identified over 200 targeted by approved drugs, highlighting their impact on disease-relevant
pathways. This comprehensive atlas, available as an open-access resource
https://cbmr.ku.dk/research/research-groups/deshmukh-group/shiny-apps/, advances our
molecular insight into exercise adaptations and enables exerkine discovery, biomarker
development, and pharmacological exercise-mimetic strategies. Less
The Olink Explore platform enables high-throughput protein biomarker discovery through Proximity Extension Assay PEA technology combined with Next Generation Sequencing NGS on Illumina instruments This approach allows for the simultaneous measurement of thousands of human plasma proteins with minimal sample volumes The Explore library offers approximately protein assays while the smaller Explore -plex panels cater to more targeted studies The platform excels in detecting low-abundance proteins such as cytokines and chemokines and is particularly effective for challenging sample types like cerebrospinal fluid CSF where protein content is typically low In this chapter we emphasize critical dry-lab considerations including CSF handling ... More
The Olink® Explore platform enables high-throughput protein biomarker discovery through Proximity Extension Assay (PEA) technology combined with Next Generation Sequencing (NGS) on Illumina instruments. This approach allows for the simultaneous measurement of thousands of human plasma proteins with minimal sample volumes. The Explore 3072 library offers approximately 3000 protein assays, while the smaller Explore 384-plex panels cater to more targeted studies. The platform excels in detecting low-abundance proteins, such as cytokines and chemokines, and is particularly effective for challenging sample types like cerebrospinal fluid (CSF), where protein content is typically low. In this chapter, we emphasize critical dry-lab considerations, including CSF handling, study design, sample size determination, instrumentation requirements, and post-experiment data management. Proper planning and execution of these factors are essential for optimizing performance and ensuring reliable outcomes when using Olink®'s platform. Less
While contemporary short-read single cell RNA-sequencing allows to decipher tissue composition discrimination between transcript isoforms remains challenging Here we propose single cell long-read isoform sequencing scLIS-seq and highlight its performance on Jurkat and HEK T cells in direct comparison to Smart-seq xpress SS X scLIS-seq demonstrates sensitive gene and transcript detection with high correlation compared to SS X and detects at least isoforms of over genes while of the reads supported novel isoforms Direct comparison of the scLIS-seq isoforms to SS X-reconstructed isoforms demonstrated scLIS-seq s superiority Overall scLIS-seq provides a powerful scRNA-seq strategy enabling long-read transcriptome analysis and isoform ... More
While contemporary short-read single cell RNA-sequencing allows to decipher tissue composition, discrimination between transcript isoforms remains challenging. Here, we propose single cell long-read isoform sequencing (scLIS-seq), and highlight its performance on Jurkat and HEK293T cells in direct comparison to Smart-seq3xpress (SS3X). scLIS-seq demonstrates sensitive gene and transcript detection with high correlation compared to SS3X and detects at least 10 isoforms of over 2600 genes, while 17.1–21.6% of the reads supported novel isoforms. Direct comparison of the scLIS-seq isoforms to SS3X-reconstructed isoforms demonstrated scLIS-seq’s superiority. Overall, scLIS-seq provides a powerful scRNA-seq strategy, enabling long-read transcriptome analysis and isoform detection. Less
High-throughput experimentation HTE is a critical tool in modern pharmaceutical discovery and development The ability to perform multiple parallel experiments in miniaturized plate-based formats has revolutionized how chemical reactions are optimized HTE has been especially enabling for catalytic reactions where the complexity of factors influencing the outcome makes the HTE approach especially suitable We detail AstraZeneca s -year journey with HTE from early beginnings to a global community of HTE specialists that are critical to the delivery of our complex portfolio with reduced environmental impact With an emphasis on catalytic reactions we provide relevant case study examples from across discovery ... More
High-throughput experimentation (HTE) is a critical tool in modern pharmaceutical discovery and development. The ability to perform multiple parallel experiments in miniaturized plate-based formats has revolutionized how chemical reactions are optimized. HTE has been especially enabling for catalytic reactions, where the complexity of factors influencing the outcome makes the HTE approach especially suitable. We detail AstraZeneca’s 20-year journey with HTE, from early beginnings to a global community of HTE specialists that are critical to the delivery of our complex portfolio with reduced environmental impact. With an emphasis on catalytic reactions, we provide relevant case study examples from across discovery and development, discuss current technology, data science and workflows, and provide insights into where we see future advances in HTE. Less
Transglutaminases TGases are a family of calcium-dependent enzymes primarily known for their ability to cross-link proteins Transglutaminase TG is one isozyme in this family whose role is multifaceted TG can act not only as a typical transamidase through its catalytic core but also as a G-protein via its GTP binding site These two discrete activities are tightly regulated by both environmental stimuli and redox reactions Ubiquitously expressed in humans TG has been implicated in numerous disease pathologies that require extensive investigation The catalytic activity of TG can be monitored through various mechanisms including hydrolysis transamidation or cleavage of isopeptide bonds ... More
Transglutaminases (TGases) are a family of calcium-dependent enzymes primarily known for their ability to cross-link proteins. Transglutaminase 2 (TG2) is one isozyme in this family whose role is multifaceted. TG2 can act not only as a typical transamidase through its catalytic core but also as a G-protein via its GTP binding site. These two discrete activities are tightly regulated by both environmental stimuli and redox reactions. Ubiquitously expressed in humans, TG2 has been implicated in numerous disease pathologies that require extensive investigation. The catalytic activity of TG2 can be monitored through various mechanisms, including hydrolysis, transamidation, or cleavage of isopeptide bonds. Activity assays are required to monitor the activity of this isozyme not only for studying its transamidation reaction but also for validation of therapeutics designed to abolish this activity. Herein, we present the design, synthesis, and evaluation of a new TG2 activity substrate based on a previously optimized inhibitor scaffold. The substrate APH7 exhibits excellent affinity, selectivity, and reactivity with TG2 (KM = 3.0 μM). Furthermore, its application also allowed the discovery of unique hysteresis at play within the catalytic activity and inhibition reactivity of TG2. Less