Biology subjects

Johansson, C.

Publications and source records attributed to Johansson, C..

10 recordsLinked to original sources

bioRxiv2026

Aerodynamic performance appears to have shaped the evolution of flight-feather microstructures

Flight feather structures - shaft, barbs, and barbules - have transformed through evolution. Although size, shape and orientation of these structures likely influence the aerodynamic performance of the feathers, their impact remains unclear. Here we investigated the feather structures influence on flow and aerodynamic performance, using computational fluid dynamic modelling, by modifying the morphology of a section of a Jackdaw (Corvus monedula) flight feather. We show that the flow over the leading vane is a key factor, and that changing the barb-to-shaft angle from its natural state as well as the trailing vane barb angle, reduces performance, which could explain evolutionary changes from early Paraves species. All in all, our results suggest that current feather composition may be close to a local maximum for both aerodynamic efficiency and stability/flow predictability, suggesting evolution of feather structures have been driven by aerodynamic performance, which should have implications for designing bio-inspired technologies.

zoology↗

bioRxiv2026

Wing pitch timing and wing elevation modulate forces and body pitch in forward flapping flight

Aerodynamic performance in flying animals can be controlled not only by changes in wing shape and size, but also by changes in wing motion. In flapping wings, the two wings interact aerodynamically, where the interaction depends on wingbeat phase, wing proximity, and wing attitude. Although, observations of free-flying animals show wings are relatively close during forward flight, how these interactions influence force production remain unclear. Here we used a robotic flapping wing and quantitative flow measurements to test the effect of wing interactions while varying mean wing elevation and pitch timing during upstroke-downstroke transitions. We show that both force magnitude and direction depend strongly on these parameters and their interaction. The fitted response models showed that high wing position combined with early pitching maximized vertical force, whereas low-to-mid wing position with synchronized-to-late pitching increased thrust. Efficiency metrics were highest near mid-to-high wing position combined with late pitching. In addition, we found that transition phases strongly affected thrust generation and produced substantial body pitch torques. These findings demonstrate that small kinematic adjustments can markedly alter aerodynamic performance and be used for tailless flight control. This offers mechanistic explanations for observed animal wing motions and novel strategies for controlling flapping drones.

zoology↗

bioRxiv2025

The Rise and Fall of SARM1 Base-Exchange Inhibitors

The sterile alpha and TIR motif containing 1 (SARM1) enzyme is a key driver of axonal degeneration in response to injury, making it an attractive target for treating chemotherapy-induced peripheral neuropathy (CIPN) and other nervous system diseases. In this study, we identified and optimised a new class of base-exchange inhibitors (BEXi) targeting SARM1 and explored their molecular interactions and conformational effects using cryo-EM, HDX-MS and SAXS. Although BEXi produced robust inhibition across all biochemical and cellular assay formats, application at sub-inhibitory concentrations consistently led to paradoxical SARM1 activation, and in neuronal assays, accelerated neurite degeneration. Further analysis showed that BEXi only delayed, rather than prevented, neurite degeneration when applied to primary neuronal cells, even at exceedingly high inhibitor concentrations. These results prompted us to discontinue BEXi development in favour of alternative strategies, underscoring the complexity of SARM1 as a therapeutic target and the need for comprehensive, mechanistically informed screening cascades.

neuroscience↗

bioRxiv2025

Integrating Cell Painting and Thermal Proteome Profiling for Inference of Targets and Mechanism of Action

Understanding the mechanism of action (MoA) of bioactive compounds is a central challenge in drug discovery and chemical biology. In this article, we propose a strategy for integrating morphological data with proteomics to provide deeper insights into the MoA of compounds. We combine the rich phenotypic profiles of Cell Painting (CP) with the unbiased protein target detection of Thermal Proteome Profiling (TPP), and construct protein-protein interaction networks based on potential targets identified using both assays. We evaluate our method on public TPP data sets for the five compounds (+)-JQ1, I-BET151, Vemurafenib, Crizotinib and Panobinostat, together with Cell Painting data for 5270 drugs on U2OS cells. We show that the combined approach could accurately identify known MoAs for four out of five compounds. This work highlights the value of multimodal profiling for chemical biology and opens new avenues for data-driven discovery of therapeutic mechanisms.

bioinformatics↗

bioRxiv2024

Type I interferons induced upon respiratory viral infection impair lung metastatic initiation

Invasive breast cancer accounts for 7% of all cancer-related deaths, with the lungs being a common site of metastases. At the same time, lower respiratory tract infections are a common cause of morbidity and mortality worldwide. Acute viral respiratory infections induce transitional changes in the lung; however, the impact of these changes on metastasis initiation and cancer progression remains unclear. Using primary murine MMTV-PyMT breast cancer cells in an experimental lung metastasis model, we show that changes induced by respiratory syncytial virus (RSV) infection impair tumor cell seeding and early establishment in the lung, resulting in lower number of metastatic nodules. Furthermore, we demonstrate that this reduction of metastases is due to alterations in the lung environment mediated by type I interferons (IFNs) that are produced in response to RSV infection. Consistent with that notion, intranasal administration of recombinant IFN- recapitulates the anti-tumor effect of RSV infection. Type I IFNs change the lung cellular composition and induce an Interferon Stimulated Gene (ISG) driven response, creating an alveolar environment that is less supportive of tumor cell growth. Indeed, epithelial cells from mice infected with RSV or intranasally exposed to IFN-, are less supportive of tumor cell growth ex vivo. Altogether, our results suggest that type I IFNs induced by infection with some respiratory viruses perturb the lungs and consequently interfere with the ability of tumor cells to successfully initiate metastatic colonization. SignificanceWomen diagnosed with metastatic breast cancer have a low survival rate. The lungs are a common metastatic site and are constantly exposed to viral pathogens, such as coronavirus, RSV and influenza virus. Thus, breast cancer and respiratory virus infection are likely to co-occur, but their interplay remains unclear. We show that type I interferons (IFNs), induced upon viral infection impair metastatic cancer cell seeding of mouse lungs. This is potentially via an effect of IFNs on lung epithelial cells, which become less supportive of early tumor cell proliferation. These findings indicate that viral infections and type I IFNs can alter the lung environment and impair implantation of metastatic cells, which could be explored to improve future cancer treatments.

immunology↗

bioRxiv2024

Feather aerodynamics suggest importance of lift and flow predictability over drag minimization

Partly overlapping feathers form a large part of birds wing surfaces, but in many species the outermost feathers split, making each feather function as an independent wing. These feathers are complex structures that evolved to fulfil both aerodynamic and structural functions. Yet relatively little is known about how the profile shape and microstructures of feathers impact aerodynamic performance. Here we determined, using fluid dynamic modelling, the aerodynamic capabilities of a section of the primary flight feather forming the leading edge of the split wing tip of a Jackdaw (Corvus monedula). Our findings demonstrate that the feather section exhibits a relatively high performance, with lift comparable to manmade aerofoils, however, there is a drag penalty associated with the feather shaft. The models vortex shedding behaviour shows low amplitude temporal fluctuations in lift, compared to manmade aerofoils. Notably, the aerodynamic pitch torque around the shaft varies with angle of attack. This, when combined with the built-in pitch-up twist of the feather implies a passive pitch control mechanism for the feather. Taken together, our findings suggest evolutionary adaptations of the flow around the feather, which could be of interest when designing micro-air vehicles and wind turbines. O_TBL View this table: org.highwire.dtl.DTLVardef@658851org.highwire.dtl.DTLVardef@1d8a3fforg.highwire.dtl.DTLVardef@1f6e34dorg.highwire.dtl.DTLVardef@1c4e085org.highwire.dtl.DTLVardef@7065b3_HPS_FORMAT_FIGEXP M_TBL C_TBL

zoology↗

bioRxiv2023

TLR7 activation at epithelial barriers promotes emergency myelopoiesis and lung anti-viral immunity

Monocytes are heterogeneous innate effector leukocytes generated in the bone marrow and released into circulation in a CCR2-dependent manner. During infection or inflammation myelopoiesis is modulated to rapidly meet demand for more effector cells. Danger signals from peripheral tissues can influence this process. Herein we demonstrate that repetitive TLR7 stimulation via the epithelial barriers drove a potent emergency bone marrow monocyte response. This process was unique to TLR7 activation and occurred independently of the canonical CCR2 and CX3CR1 axes or prototypical cytokines. The monocytes egressing the bone marrow had an immature Ly6C-high profile and differentiated into vascular Ly6C-low monocytes and tissue macrophages in multiple organs. They displayed a blunted cytokine response to further TLR7 stimulation and reduced lung viral load after RSV and influenza virus infection. These data provide insights into the emergency myelopoiesis likely to occur in response to the encounter of single-stranded RNA viruses at barrier sites.

immunology↗

bioRxiv2021

Evaluation of the speed, accuracy and precision of the QuickMIC rapid antibiotic susceptibility testing assay in a clinical setting

The rapidly changing landscape of antimicrobial resistance poses a challenge for empirical antibiotic therapy in severely ill patients and highlights the need for fast antibiotic susceptibility diagnostics to guide treatment. Traditional methods for antibiotic susceptibility testing (AST) of bacteria such as broth microdilution (BMD) or the disc diffusion method (DDM) are comparatively slow and show high variability. Rapid AST methods under development often trade speed for resolution, sometimes only measuring responses at a single antibiotic concentration. QuickMIC is a recently developed lab-on-a-chip system for rapid AST. Here we evaluate the performance of the QuickMIC method with regard to speed, precision and accuracy in comparison to traditional diagnostic methods. 151 blood cultures of clinical Gram-negative isolates with a high frequency of drug resistance were tested with the QuickMIC system and compared with BMD for 12 antibiotics. To investigate sample turnaround time and functionality in a clinical setting, another 41 clinical blood culture samples were acquired from the Uppsala University Hospital and analyzed on site in the clinical laboratory with the QuickMIC system, and compared with DDM for 8 antibiotics routinely used in the clinical laboratory. The overall essential agreement between MIC values obtained by QuickMIC and BMD was 83.2%, with an average time to result of 3 h 2 min (SD: 24.8 min) for the QuickMIC method. For the clinical dataset, the categorical agreement was 94.9%, and the total turnaround time as compared to routine diagnostics reduced by 40% (33 h vs. 55 h). Interexperiment variability was low (average SD: 44.6% from target MIC) compared to the acceptable standard of {+/-}1 log2 unit (i.e. -50% to +100% deviation from target MIC) in BMD. We conclude that the QuickMIC method can provide rapid and accurate AST, and may be especially valuable in settings with high resistance rates and for antibiotics where wildtype and resistant MIC distributions are close or overlapping.

microbiology↗

bioRxiv2021

The Prolyl-tRNA Synthetase Inhibitor Halofuginone Inhibits SARS-CoV-2 Infection

Summary ParagraphWe identify the prolyl-tRNA synthetase (PRS) inhibitor halofuginone1, a compound in clinical trials for anti-fibrotic and anti-inflammatory applications2, as a potent inhibitor of SARS-CoV-2 infection and replication. The interaction of SARS-CoV-2 spike protein with cell surface heparan sulfate (HS) promotes viral entry3. We find that halofuginone reduces HS biosynthesis, thereby reducing spike protein binding, SARS-CoV-2 pseudotyped virus, and authentic SARS-CoV-2 infection. Halofuginone also potently suppresses SARS-CoV-2 replication post-entry and is 1,000-fold more potent than Remdesivir4. Inhibition of HS biosynthesis and SARS-CoV-2 infection depends on specific inhibition of PRS, possibly due to translational suppression of proline-rich proteins. We find that pp1a and pp1ab polyproteins of SARS-CoV-2, as well as several HS proteoglycans, are proline-rich, which may make them particularly vulnerable to halofuginones translational suppression. Halofuginone is orally bioavailable, has been evaluated in a phase I clinical trial in humans and distributes to SARS-CoV-2 target organs, including the lung, making it a near-term clinical trial candidate for the treatment of COVID-19.

microbiology↗

bioRxiv2020

ObLiGaRe doxycycline Inducible (ODIn) Cas9 system driving pre-clinical drug discovery, from design to cancer treatment

The CRISPR-Cas9 system has increased the speed and precision of genetic editing in cells and animals. However, model generation for drug development is still expensive and time-consuming, demanding more target flexibility and faster turnaround times with high reproducibility. We have generated a tightly controlled ObLiGaRe doxycycline inducible SpCas9 (ODInCas9) transgene. Targeted ObLiGaRe resulted in functional integration into both human and mouse cells culminating in the generation of the ODInCas9 mouse. Genomic editing can be performed in cells of various tissue origins without any detectable gene editing in the absence of doxycycline. Somatic in vivo editing can model non-small cell lung cancer (NSCLC) adenocarcinomas, enabling treatment studies to validate the efficacy of candidate drugs. The ODInCas9 mouse can be utilized for robust and tunable genome editing allowing for flexibility, speed and uniformity at reduced cost, leading to high throughput and practical preclinical in vivo therapeutic testing.

genomics↗