Biology subjects

Andersson, J.

Publications and source records attributed to Andersson, J..

14 recordsLinked to original sources

bioRxiv2025

LubriShieldTM - a unique permanent coating for indwelling urinary catheters that impedes surface-associated uropathogens from forming biofilm

Catheter-associated urinary tract infection (CAUTI) is one of the most common healthcare-associated infections and biofilm formation plays a key role in its pathogenesis. Indwelling medical devices introduce ideal pathways inside the body for invading pathogens and feature surfaces conducive to biofilm development. These devices are the root cause of severe clinical infections often recalcitrant to antimicrobials. When bacteria and fungi switch to biofilm mode of growth, they produce a matrix in the form of extracellular polymeric substances (EPS). This creates a unique environment for growing virulent colonizers and persisting cells while also forming a shielding barrier against immune system attacks, antimicrobial agents and mechanical removal by fluid shear forces. To address this challenge, LubriShield TM - a novel permanent coating was invented, and evenly applied to both the internal and external surfaces of indwelling urinary Foley catheters. Without releasing active substances, it effectively prevented pathogens from producing biofilm. The coating was superhydrophilic and incorporated a proprietary anti-fouling ligand, which created a surface that significantly inhibited up to 99% of colonizing uropathogens from forming biofilm for the duration of use without any microbial killing (p< 0.001). The predominant uropathogens, including Gram-positive and Gram-negative as well as Candida albicans, were inhibited from forming biofilm on the LubriShieldTM coated surfaces for up to 14 days in artificial urine medium. After challenging the adhering bacteria in a glass bladder flow model, the coating still significantly reduced biofilm formation by 83% (p<0.001). The growth mode and emergent properties of adhering bacteria on uncoated silicone catheter surfaces were compared with those on LubriShieldTM coated surfaces. RNA-seq analysis revealed that gene expression associated with microbial EPS formation was significantly downregulated on the coated surfaces. Additionally, microorganisms adhering to LubriShieldTM coated catheters were 46% more susceptible to antibiotics compared to those on uncoated silicone catheters (p<0.01).

microbiology↗

bioRxiv2024

5' HOXD Genes Differentially Regulate Gene Expression of Synovial Fibroblasts in Hand Joints

We previously demonstrated that Homeobox (HOX) transcription factors are differentially expressed between joint locations and can accurately assign synovial fibroblasts (SFs) to their correct joint location. We show here that the expression of the 5HOXD transcription factors HOXD10, HOXD11, and HOXD13 in SFs strikingly overlaps with predilection sites for the development of rheumatoid arthritis (RA). Changes in SFs gene expression after silencing 5HOXDs aligned with joint-specific differences of RA SFs. In particular, we identify HOXD13 as regulator or primary cilia function in SFs modulating cell cycle, DNA damage and proteasome activity. Accordingly, we show joint specific differences in primary cilia morphology, DNA damage repair and proteasome activity. We thus propose that HOXD13 and primary cilia play a role in shaping joint-specific SFs functions that might underlie the pathognomic pattern of joint involvement in RA.

cell biology↗

bioRxiv2024

HOXB6 and HOXB8 control immune-cancer cell interactions in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer lacking effective drugs and therefore new treatment targets are needed. Transcriptomic analysis comparing human embryonic and PDAC tissue identified a large overlap of expression profiles suggesting a re-initiation of developmental programs in pancreatic cancer. Specifically, we identified the transcription factors HOXB6 and HOXB8 as potential key regulators in PDAC. Loss of HOXB6 and HOXB8 in pancreatic cancer cells inhibited cell proliferation, induced apoptosis and senescence and enhanced gemcitabine sensitivity. Moreover, reduced HOXB6 and HOXB8 expression in pancreatic and lung adenocarcinoma cell lines affected transcription of immune response pathways which resulted in an increased sensitivity of cancer cells to anti-tumorigenic activities of macrophages suggesting that the HOXB6 and HOXB8 immune regulatory pattern is conserved in different cancer types. Additionally, naive M0 macrophages exposed to HOXB8 deficient PDAC cells were unable to differentiate into tumor associated macrophages, suggesting that HOXB8 promotes the transition of initial anti-tumor macrophage to a tumor-promoting macrophage phenotype in pancreatic cancer. Our findings indicate that HOXB6 and HOXB8 play important roles in regulating cell proliferation, immune response and treatment resistance to promote pancreatic cancer tumorigenesis and could be useful therapeutic targets.

cancer biology↗

bioRxiv2023

E2F transcription factors promote tumorigenicity in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with limited treatment options, illustrating an urgent need to identify new drugable targets in PDACs. Using the similarities between tumor development and normal embryonic development, which is accompanied by rapid cell expansion, we identified embryonic signalling pathways that were reinitiated during tumor formation and expansion. Here, we report that the transcription factors E2F1 and E2F8 are potential key regulators in PDAC. E2F1 and E2F8 RNA expression is mainly localized in proliferating cells in the developing pancreas and in malignant ductal cells in PDAC. Silencing of E2F1 and E2F8 in PANC-1 pancreatic tumor cells inhibited cell proliferation and impaired cell spreading and migration. Moreover, loss of E2F1 also affected cell viability and apoptosis with E2F expression in PDAC tissues correlating with expression of apoptosis and mitosis pathway genes, suggesting that E2F factors promote cell cycle regulation and tumorigenesis in PDAC cells. In conclusion, our findings show that E2F1 and E2F8 transcription factors regulate cell proliferation, survival, and migration during pancreatic carcinogenesis.

cancer biology↗

bioRxiv2023

Platelet-specific TGFβ1 deficiency aggravates atherosclerosis, vascular inflammation, and hypercholesterolemia in mice

Atherosclerosis involves inflammatory and thrombotic mechanisms, to which both platelets and transforming growth factor {beta} (TGF{beta}) contribute. The effect of platelet-derived TGF{beta} on atherosclerosis is, however, unknown and therefore investigated. Murine platelet-selective TGF{beta}-deficiency (plt-TGF{beta}-/-) was created by a Pf4-Cre approach, and an atherosclerotic mouse model was established by functional abrogation of Ldlr and 10-15 weeks of a high-fat diet in plt-TGF{beta}-/- mice and their non-plt-TGF{beta}-/- littermates. En face Oil Red O staining of the aorta showed more atherosclerotic lesion formation in plt-TGF{beta}-/- mice, with significant increases in both lesion size and lesion coverage of the total aortic area. Cryosections of the aortic root confirmed the aggravation of atherogenesis. Platelet-derived TGF{beta} deficiency increased circulating platelets and plasma levels of total cholesterol, LDL-cholesterol, and triglycerides after a 10 or 15 week high-fat diet period. RNA sequencing and proteomic analyses of the aorta showed signs of CD4+ T effector cell and macrophage activation in plt-TGF{beta}-/- mice. In conclusion, platelet-specific TGF{beta} deficiency aggravates atherosclerosis, via increasing arterial inflammation and plasma levels of cholesterol. Our findings demonstrate that platelet-derived TGF{beta} is prominently athero-protective. Key pointsO_LIPlatelet-specific transforming growth factor {beta} (TGF{beta}) deficiency markedly enhances atherosclerosis in a high-fat diet-fed murine model. C_LIO_LIPlatelet TGF{beta} deficiency aggravates hyperlipidemia, with further elevations of total cholesterol, LDL-cholesterol, and triglycerides. C_LI

cell biology↗

bioRxiv2023

Objective QC for diffusion MRI data: artefact detection using normative modelling

Diffusion MRI is a neuroimaging modality used to evaluate brain structure at a microscopic level and can be exploited to map white matter fibre bundles and microstructure in the brain. One common issue is the presence of artefacts, such as acquisition artefacts, physiological artefacts, distortions or image processing-related artefacts. These may lead to problems with other downstream processes and can bias subsequent analyses. In this work we use normative modelling to create a semi-automated pipeline for detecting diffusion imaging artefacts and errors by modelling 24 white matter imaging derived phenotypes from the UK Biobank dataset. The considered features comprised 4 microstructural features (from models with different complexity such as fractional anisotropy and mean diffusivity from a diffusion tensor model and parameters from neurite orientation, dispersion and density models), each within six pre-selected white matter tracts of various sizes and geometrical complexity (corpus callosum, bilateral corticospinal tract and uncinate fasciculus and fornix). Our method was compared to two traditional quality control approaches: a visual quality control protocol performed on 500 subjects and quantitative quality control using metrics derived from image pre-processing. The normative modelling framework proves to be comprehensive and efficient in detecting diffusion imaging artefacts arising from various sources (such as susceptibility induced distortions or motion), as well as outliers resulting from inaccurate processing (such as erroneous spatial registrations). This is an important contribution by virtue of this methods ability to identify the two problem sources (i) image artefacts and (ii) processing errors, which subsequently allows for a better understanding of our data and informs on inclusion/exclusion criteria of participants.

neuroscience↗

bioRxiv2022

Seasonal eDNA-based monitoring of Batrachochytrium dendrobatidis and amphibian species in Norway

Freshwaters represent the most threatened environments with regard to biodiversity loss and therefore there is a need for national monitoring programs to effectively document species distribution and evaluate potential risks for vulnerable species. The monitoring of species for effective management practices is, however, challenged by insufficient data acquisition when using traditional methods. Here we present the application of environmental DNA (eDNA) metabarcoding of amphibians in combination with quantitative PCR assays for an invasive pathogenic chytrid species (Batrachochytrium dendrobatidis-Bd), a potential threat to endemic and endangered amphibian species. Statistical comparison of amphibian species detection using either traditional or eDNA-based approaches showed weak correspondence. By tracking the distribution of Bd over three years, we concluded that the risk for amphibian extinction is low since Bd was only detected at five sites where multiple amphibians were present over the sampled years. Our results show that eDNA-based detection can be used for simultaneous monitoring of amphibian diversity and the presence of amphibian pathogens at the national level in order to assess potential species extinction risks and establish effective management practices. As such our study represents suggestions for a national monitoring program based on eDNA.

ecology↗

bioRxiv2021

Transport receptor occupancy in Nuclear Pore Complex mimics

Nuclear Pore Complexes (NPCs) regulate all molecular transport between the nucleus and the cytoplasm in eukaryotic cells. Intrinsically disordered Phe-Gly nucleoporins (FG Nups) line the central conduit of NPCs to impart a selective barrier where large proteins are excluded unless bound to a transport receptor (karyopherin; Kap). Here, we assess Kap-centric NPC models, which postulate that Kaps participate in establishing the selective barrier. We combine biomimetic nanopores, formed by tethering Nsp1 to the inner wall of a solid-state nanopore, with coarse-grained modeling to show that yeast Kap95 exhibits two populations in Nsp1-coated pores: one population that is transported across the pore in milliseconds, and a second population that is stably assembled within the FG mesh of the pore. Ionic current measurements show a conductance decrease for increasing Kap concentrations and noise data indicate an increase in rigidity of the FG-mesh. Modeling reveals an accumulation of Kap95 near the pore wall, yielding a conductance decrease. We find that Kaps only mildly affect the conformation of the Nsp1 mesh and that, even at high concentrations, Kaps only bind at most 8% of the FG-motifs in the nanopore, indicating that Kap95 occupancy is limited by steric constraints rather than by depletion of available FG-motifs. Our data provide an alternative explanation of the origin of bimodal NPC binding of Kaps, where a stable population of Kaps binds avidly to the NPC periphery, while fast transport proceeds via a central FG-rich channel through lower affinity interactions between Kaps and the cohesive domains of Nsp1.

biophysics↗

bioRxiv2020

Multimodal imaging brain markers in early adolescence are linked with a physically active lifestyle

The World Health Organization (WHO) promotes physical exercise and a healthy lifestyle as means to improve youth development. However, relationships between physical lifestyle and brain development are not fully understood. Here, we asked whether a brain - physical latent mode of covariation underpins the relationship between physical activity, fitness, and physical health measures with multimodal neuroimaging markers. In 50 12-year old school pupils (26 females), we acquired multimodal whole-brain MRI, characterizing brain structure, microstructure, function, myelin content, and blood perfusion. We also acquired physical variables measuring objective fitness levels, 7-days physical activity, body-mass index, heart rate, and blood pressure. Using canonical correlation analysis we unravel a latent mode of brain - physical covariation, independent of demographics, school, or socioeconomic status. We show that MRI metrics with greater involvement in this mode also showed spatially extended patterns across the brain. Specifically, global patterns of greater grey matter perfusion, volume, cortical surface area, greater white matter extra-neurite density, and resting state networks activity, covaried positively with measures reflecting a physically active phenotype (high fit, low sedentary individuals). Showing that a physically active lifestyle is linked with systems-level brain MRI metrics, these results suggest widespread associations relating to several biological processes. These results support the notion of close brain-body relationships and underline the importance of investigating modifiable lifestyle factors not only for physical health but also for brain health early in adolescence. Significance statementAn active lifestyle is key for healthy development. In this work, we answer the following question: How do brain neuroimaging markers relate with young adolescents level of physical activity, fitness, and physical health? Combining advanced whole-brain multimodal MRI metrics with computational approaches, we show a robust relationship between physically active lifestyles and spatially extended, multimodal brain imaging derived phenotypes. Suggesting a wider effect on brain neuroimaging metrics than previously thought, this work underlies the importance of studying physical lifestyle, as well as other brain - body relationships in an effort to foster brain health at this crucial stage in development.

neuroscience↗

bioRxiv2020

Variable environments select for short lifespan

The role of environmental variation in the evolution of lifespan is contested. Classic theory predicts that variable environments favour the evolution of long life, but recent theoretical work suggests that environmental variation can instead select for shorter lifespan when the changes are rapid relative to generation time. Here, we used experimental evolution to study how lifespan evolves in response to temperature variation. Genetically diverse populations of the outcrossing nematode Caenorhabditis remanei, were exposed to a novel, stressful temperature for 30 generations, under stable, gradually warming or fluctuating thermal regimes. We found the evolution of shorter lifespan in populations exposed to environments that fluctuated within the individuals lifetime, compared to populations evolving in stable warm temperature. While climate warming is predicted to increase environmental stochasticity, our results show that fast temperature cycles can rapidly select for short lifespan.

evolutionary biology↗

bioRxiv2020

The Developing Human Connectome Project: typical and disrupted functional connectivity across the perinatal period

The Developing Human Connectome Project (dHCP) is an Open Science project which provides the first large sample of neonatal functional MRI (fMRI) data with high temporal and spatial resolution. This data enables mapping of intrinsic functional connectivity between spatially distributed brain regions under normal and adverse perinatal circumstances, offering a framework to study the ontogeny of large-scale brain organisation in humans. Here, we characterise in unprecedented detail the maturation and integrity of resting-state networks (RSNs) at normal term age in 337 infants (including 65 born preterm). First, we applied group independent component analysis (ICA) to define 11 RSNs in term-born infants scanned at 43.5-44.5 weeks postmenstrual age (PMA). Adult-like topography was observed in RSNs encompassing primary sensorimotor, visual and auditory cortices. Among six higher-order, association RSNs, analogues of the adult networks for language and ocular control were identified, but a complete default mode network precursor was not. Next, we regressed the subject-level datasets from an independent cohort of infants scanned at 37-43.5 weeks PMA against the group-level RSNs to test for the effects of age, sex and preterm birth. Brain mapping in term-born infants revealed areas of positive association with age across four of six association RSNs, indicating active maturation in functional connectivity from 37 to 43.5 weeks PMA. Female infants showed increased connectivity in inferotemporal regions of the visual association network. Preterm birth was associated with striking impairments of functional connectivity across all RSNs in a dose-dependent manner; conversely, connectivity of the superior parietal lobules within the lateral motor network was abnormally increased in preterm infants, suggesting a possible mechanism for specific difficulties such as developmental coordination disorder which occur frequently in preterm children. Overall, we find a robust, modular, symmetrical functional brain organisation at normal term age. A complete set of adult-equivalent primary RSNs is already instated, alongside emerging connectivity in immature association RSNs, consistent with a primary-to-higher-order ontogenetic sequence of brain development. The early developmental disruption imposed by preterm birth is associated with extensive alterations in functional connectivity.

neuroscience↗

bioRxiv2019

The developing Human Connectome Project (dHCP) automated resting-state functional processing framework for newborn infants.

The developing Human Connectome Project (dHCP) aims to create a detailed 4-dimensional connectome of early life spanning 20 to 45 weeks post-menstrual age. This is being achieved through the acquisition of multi-modal MRI data from over 1000 in- and ex-utero subjects combined with the development of optimised pre-processing pipelines. In this paper we present an automated and robust pipeline to minimally pre-process highly confounded neonatal resting-state fMRI data, robustly, with low failure rates and high quality-assurance. The pipeline has been designed to specifically address the challenges that neonatal data presents including low and variable contrast and high levels of head motion. We provide a detailed description and evaluation of the pipeline which includes integrated slice-to-volume motion correction and dynamic susceptibility distortion correction, a robust multimodal registration approach, bespoke ICA-based denoising, and an automated QC framework. We assess these components on a large cohort of dHCP subjects and demonstrate that processing refinements integrated into the pipeline provide substantial reduction in movement related distortions, resulting in significant improvements in SNR, and detection of high quality RSNs from neonates. HighlightsO_LIAn automated and robust pipeline to minimally pre-process highly confounded neonatal fMRI data C_LIO_LIIncludes integrated dynamic distortion and slice-to-volume motion correction C_LIO_LIA robust multimodal registration approach which includes custom neonatal templates C_LIO_LIIncorporates an automated and self-reporting QC framework to quantify data quality and identify issues for further inspection C_LIO_LIData analysis of 538 infants imaged at 26-45 weeks post-menstrual age C_LI

neuroscience↗

bioRxiv2019

Environmental variation mediates the evolution of anticipatory parental effects

Theory maintains that when future environment is predictable, parents should adjust the phenotype of their offspring to match the anticipated environment. The plausibility of positive anticipatory parental effects is hotly debated and the experimental evidence for the evolution of such effects is currently lacking. We experimentally investigated the evolution of anticipatory maternal effects in a range of environments that differ drastically in how predictable they are. Populations of the nematode Caenorhabditis remanei, adapted to 20{degrees}C, were exposed to a novel temperature (25{degrees}C) for 30 generations with either positive or zero correlation between parent and offspring environment. We found that populations evolving in novel environments that were predictable across generations evolved a positive anticipatory maternal effect, since they required maternal exposure to 25{degrees}C to achieve maximum reproduction in that temperature. In contrast, populations evolving under zero environmental correlation had lost this anticipatory maternal effect. Similar but weaker patterns were found if instead rate-sensitive population growth was used as a fitness measure. These findings demonstrate that anticipatory parental effects evolve in response to environmental change so that ill-fitting parental effects can be rapidly lost. Evolution of positive anticipatory parental effects can aid population viability in rapidly changing but predictable environments. Impact summaryParents can help their offspring by adjusting offsprings phenotype to match their environment. Such anticipatory parental effects would be beneficial, but only if parents can accurately predict the environment in which their offspring will develop and live. The plausibility of such anticipatory parental effects is hotly debated. The theory is clear that the predictability of the environment should play a defining role. We used an "experimental evolution" approach in a fast reproducing nematode worm Caenorhabditis remanei to tackle this question and follow the evolution of parental effects in different environments in real-time. We found that populations evolving in a novel but predictable environment indeed had anticipatory parental effects that increased fitness of their offspring in that environment. In contrast, when evolving in an unpredictable environment where such parental effects would be disadvantageous, the parental effect was rapidly lost in evolution. Our novel experimental environments were constructed by exposing worms to increased temperature. Anticipatory parental effects play an important role in adaptation to novel environments and will affect the viability of populations under climate heating.

evolutionary biology↗

bioRxiv2018

Diffusion Acceleration with Gaussian process Estimated Reconstruction (DAGER)

PurposeImage acceleration provides multiple benefits to diffusion MRI (dMRI), with in-plane acceleration reducing distortion and slice-wise acceleration increasing the number of directions that can be acquired in a given scan time. However, as acceleration factors increase, the reconstruction problem becomes ill-conditioned, particularly when using both in-plane acceleration and simultaneous multi-slice (SMS) imaging. In this work, we develop a novel reconstruction method for in-vivo MRI acquisition that provides acceleration beyond what conventional techniques can achieve.\n\nTheory and MethodsWe propose to constrain the reconstruction in the spatial (k) domain by incorporating information from the angular (q) domain. This approach exploits smoothness of the signal in q-space using Gaussian processes, as has previously been exploited in post-reconstruction analysis. We demonstrate in-plane acceleration exceeding the theoretical parallel imaging limits, and SMS combined with in-plane acceleration at a total factor of 12. This reconstruction is cast within a Bayesian framework that incorporates estimation of smoothness hyper-parameters, with no need for manual tuning.\n\nResultsSimulations and in vivo results demonstrate superior performance of the proposed method compared with conventional parallel imaging methods. These improvements are achieved without loss of spatial or angular resolution and require only a minor modification to standard pulse sequences.\n\nConclusionThe proposed method provides improvements over existing methods for diffusion acceleration, particularly for high SMS acceleration with in-plane undersampling.

neuroscience↗