Biology subjects

Olsen, A.

Publications and source records attributed to Olsen, A..

11 recordsLinked to original sources

bioRxiv2026

Using CarboTrace 480 to detect protoplastation in pigment deficient mutant of Chlorella sorokiniana

The increasing world population necessitates new sustainable nutrient sources, making microalgae like Chlorella sorokiniana interesting due to its rich nutrient profile and sustainable cultivation methods. With genetic optimization tools like CRISPR/Cas9, microalgae as a nutrient source can be improved even further. However, degradation of the rigid cell wall of microalgae, and thereby developing protoplasts, is often necessary prior to transformation, but monitoring protoplast development in spherical, single-celled organisms like C. sorokiniana is challenging using bright-field microscopy. Carbotrace 480 and 630 were tested as fluorescent markers of the cell wall of a C. sorokiniana mutant for protoplast detection, and Carbotrace 480 was successfully used to distinguish protoplast from normal cells in a cell suspension. The enzymes Driselase, Glucanex, Snailase, and Saczyme were tested in different combinations to degrade the cell wall of the mutant, with Snailase as the most effective yielding ~60 % protoplasts. This study provides a quick and easy tool for monitoring protoplast development in the microalgae C. sorokiniana, the first step to improve C. sorokiniana as a sustainable nutrient source using genetic optimization tools like CRISPR/Cas9.

bioengineering↗

bioRxiv2024

Multiscale Quantification of Hemispheric Asymmetry in Cortical Maps Using Geometric Eigenmodes

Hemispheric asymmetry is a universal property of brain organization with wide implications into brain function and structure, and diseases. This study presents a laterality index for characterizing hemispheric asymmetries that underlie cortical maps using geometric eigenmodes derived from human cortical surfaces.We develop a generalized design to quantify asymmetries across various cortical spatial scales. While the design is individual-specific, we implement normalization steps to enable unbiased comparisons across individuals. As a proof of concept, we validated the method on cortical maps of 545 subjects across two datasets, using fMRI maps of healthy individuals and tau-PET maps of patients across the Alzheimers disease continuum. Our results reveal that cortical regions in different canonical functional networks have connectivity patterns that entail different degrees of hemispheric asymmetry. Moreover, aggregates of the pathological tau protein manifest subtle asymmetries at varying spatial scales along the disease continuum.

neuroscience↗

bioRxiv2024

Enzyme family-centred approach identifies helicases as recurrent hemizygous tumour suppressor genes

An important goal in cancer research is to identify driver genes and mutations. Reasoning that such mutations often alter enzymatic functions, we investigated the cancer driver role of enzyme families. Using pan-cancer genomic data and established driver mutation catalogues, we found an unexpectedly high rate of mutations in helicases, making helicases the most frequently mutated enzyme family in cancer. Based on both functional perturbation screens and cancer genomic analyses, we provide evidence that cancers with mutated helicases converge on increased genomic instability and faulty DNA repair. We identify a striking phenotype in cells with loss of the helicase Aquarius (AQR). AQR was exclusively hemizygous lost in cancer genomes, which was associated with elevated levels of structural variants and point mutation signatures indicative of homologous recombination deficiency. Finally, we leverage large dependency maps to show that hemizygous loss is a common tumour suppression mechanism among helicases. In summary, we uncover a striking frequency of mutated helicases with key roles in genomic maintenance, and we nominate novel hemizygous cancer driver genes including AQR.

cancer biology↗

bioRxiv2024

Genomic Epidemiology of Monkeypox Virus During the 2022 Outbreak in New York City

New York City (NYC) was one of the hotspots of monkeypox virus (MPXV) infections in the United States during the multi-country mpox outbreak in 2022. This study used the most comprehensive dataset to date to investigate the genomic characteristics of MPXV in NYC. We performed Nextclade lineage assignment, phylogenetic and mutational analyses on 1,138 specimens from 748 individuals at the NYC Public Health Lab in the context of 2,968 MPXV sequences sampled globally. Nextclade lineage assignment showed B.1.12 as a NYC specific lineage and phylogenetic analysis showed NYC and North America specific clades. The majority of mutations showed signatures of APOBEC3 activity. When looking at the intra-host genomic diversity for MPXV, distinct MPXV genomic profiles were observed in 6.4% of individuals with multiple sampled specimens, with at least 4.2% of NYC cases due to multiple MPXV infections from distinct viral strains. Further, 13% of the sequences in infected patients had a lack of concordance between epidemiologic and genetic linkages. This study identified NYC-specific MPXV genomic profiles and provided a conservative estimate of simultaneous infections with multiple MPXV variants, likely due to behavioral risk factors during the peak of the outbreak in July 2022. Improving concordance between genomic and epidemiological clusters for mpox investigations may require expanding partnerships with testing labs, clinics, and community groups to enhance the representativeness of MPXV samples that are available for sequencing.

genomics↗

bioRxiv2023

Accelerated Aging after Traumatic Brain Injury: an ENIGMA Multi-Cohort Mega-Analysis

ObjectiveThe long-term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. In light of current evidence that even a single significant brain injury event increases the risk of dementia, brain-age estimation could provide a novel and efficient indexing of the long-term consequences of TBI. Brain-age procedures use predictive modeling to calculate brain-age scores for an individual using MRI data. Complicated mild, moderate and severe TBI (cmsTBI) is associated with a higher predicted (brain) age difference (PAD), but the progression of PAD over time remains unclear. Here we sought to examine whether PAD increases as a function of time since injury (TSI). MethodsAs part of the ENIGMA Adult Moderate and Severe (AMS)-TBI working group, we examine the largest TBI sample to date (n=343), along with controls, for a total sample size of 540, to reproduce and extend prior findings in the study of TBI brain age. T1w-MRI data were aggregated across 7 cohorts and brain age was established using a similar brain age algorithm to prior work in TBI. ResultsFindings show that PAD widens with longer TSI, and there was evidence for differences between sexes in PAD, with men showing more advanced brain age. We did not find evidence supporting a link between PAD and cognitive performance. InterpretationThis work provides evidence that changes in brain structure after cmsTBI are dynamic, with an initial period of change, followed by relative stability, eventually leading to further changes in the decades after a single cmsTBI.

neuroscience↗

bioRxiv2022

Poorer Sleep Health is Associated with Altered Cognitive Control Processing in Healthy Adults

This study investigated how proactive and reactive cognitive control processing in the brain was associated with habitual sleep health. BOLD fMRI data was acquired from 81 healthy adults with normal sleep (41 females, age 20.96 - 39.58 years) during a test of cognitive control (Not-X CPT). Sleep health was assessed in the week before MRI scanning, using both objective (actigraphy) and self-report measures. Multiple measures indicating poorer sleep health - including later/more variable sleep timing, later chronotype preference, more insomnia symptoms and lower sleep efficiency - were associated with stronger and more widespread BOLD activations in fronto-parietal and subcortical brain regions during cognitive control processing (adjusted for age, sex, education, and fMRI task performance). Most associations were found for reactive cognitive control activation, indicating that poorer sleep health is linked to a hyper-reactive brain state. Analysis of time-on-task effects showed that, with longer time on task, poorer sleep health was predominantly associated with increased proactive cognitive control activation, indicating recruitment of additional neural resources over time. Finally, shorter objective sleep duration was associated with lower BOLD activation with time on task and poorer task performance. In conclusion, even in normal sleepers, relatively poorer sleep health is associated with altered cognitive control processing, possibly reflecting compensatory mechanisms and / or inefficient neural processing.

neuroscience↗

bioRxiv2022

Royal knifefish generate powerful suction feeding through large neurocranial elevation and high muscle power output

Suction feeding in ray-finned fishes involves powerful buccal cavity expansion to accelerate water and food into the mouth. Previous XROMM studies in largemouth bass (Micropterus salmoides), bluegill sunfish (Lepomis macrochirus), and channel catfish (Ictalurus punctatus) have shown that more than 90% of suction power in high performance strikes comes from the axial musculature. Thus, the shape of the axial muscles and skeleton may impact suction feeding mechanics. Royal knifefish (Chitala blanci) have an unusual postcranial morphology, with a ventrally flexed vertebral column and relatively large mass of epaxial muscle. Based on their body shape, we hypothesized that royal knifefish would generate high power strikes by utilizing large neurocranial elevation, vertebral column extension, and epaxial shortening. As predicted, C. blanci generated high suction expansion power compared to the other three species studied to date (up to 160 W), which was achieved by increasing both the rate of volume change and the intraoral subambient pressure. The large epaxial muscle (25% of body mass) shortened at high velocities to produce large neurocranial elevation and vertebral extension (up to 41 deg, combined), as well as high muscle mass-specific power (up to 800 W kg-1). For the highest power strikes, axial muscles generated 95% of the power, and 64% of the axial muscle mass consisted of the epaxial muscles. The epaxial-dominated suction expansion of royal knifefish supports our hypothesis that postcranial morphology may be a strong predictor of suction feeding biomechanics. SUMMARY STATEMENTRoyal knifefish rely on their distinct postcranial morphology--with a curved vertebral column and large dorsal body muscles--to produce large neurocranial elevation and powerful suction feeding.

zoology↗

bioRxiv2020

White Matter Disruption in Pediatric Traumatic Brain Injury: Results from ENIGMA Pediatric msTBI

Annually, approximately 3 million children around the world experience traumatic brain injuries (TBIs), of which up to 20% are characterized as moderate to severe (msTBI) and/or have abnormal imaging findings. Affected children are vulnerable to long-term cognitive and behavioral dysfunction, as injury can disrupt or alter ongoing brain maturation. Post-injury outcomes are highly variable, and there is only limited understanding of how inter-individual differences in outcomes arise. Small sample sizes have also complicated efforts to better understand factors influencing the impact of TBI on the developing brain. White matter (WM) disruption is a critical aspect of TBI neuropathology and diffusion MRI (dMRI) is particularly sensitive to microstructural abnormalities. Here we present the results of a coordinated analysis of dMRI data across ten cohorts from three countries. We had three primary aims: (1) to characterize the nature and extent of WM disruption across key post-injury intervals (acute/subacute - within 2 months, post-acute - 2-6 months, chronic - 6+ months); (2) evaluate the impact of age and sex on WM in the context of injury; and (3) to examine associations between WM and neurobehavioral outcomes. Based on data from 507 children and adolescents (244 with complicated mild to severe TBI and 263 control children), we report widespread WM disruption across all post-injury intervals. As expected, injury severity was a significant contributor to the pattern and extent of WM degradation, but explained less variance in dMRI measures with increasing time since injury, supporting other research indicating that other factors contribute increasingly to outcomes over time. The corpus callosum appears to be particularly vulnerable to injury, an effect that persists years post-TBI. We also report sex differences in the effect of TBI on the uncinate fasciculus (UNC), a structure with a key role in emotion regulation. Females with a TBI had significantly lower fractional anisotropy (FA) in the UNC than those with no TBI, and this phenomenon was further associated with more frequent parent-reported behavioral problems as measured by the Child Behavior Checklist (CBCL). These effects were not detected in males. With future harmonization of imaging and neurocognitive data, more complex modeling of factors influencing outcomes will be possible and help to identify clinically-meaningful patient subtypes.

neuroscience↗

bioRxiv2019

Using environmental DNA for the detection of Schistosoma mansoni: toward improved environmental surveillance of schistosomiasis

Schistosomiasis is a waterborne, infectious disease with high morbidity and significant economic burdens affecting more than 250 million people globally. Disease control has, with notable success, for decades focused on drug treatment of infected human populations, but a recent paradigm shift now entails moving from control to elimination. To achieve this ambitious goal more sensitive diagnostic tools are needed to monitor progress towards transmission interruption in the environment, especially in low-intensity infection areas. We report on the development of an environmental DNA (eDNA) based tool to efficiently detect DNA traces of the parasite Schistosoma mansoni directly in the aquatic environment, where the non-human part of the parasite life cycle occurs. To our knowledge, this is the first report of the successful detection of S. mansoni in freshwater samples using aquatic eDNA. True eDNA was detected in as few as 10 cercariae/L water in laboratory experiments. The field applicability of the method was tested at known transmission sites in Kenya, where comparison of schistosome detection by conventional snail surveys (snail collection and cercariae shedding) with eDNA (water samples) showed 71% agreement between the methods. The eDNA method furthermore detected schistosome presence at two additional sites where snail shedding failed, demonstrating a higher sensitivity of eDNA sampling. We conclude that eDNA provides a promising new tool to significantly improve the environmental surveillance of S. mansoni. Given the proper method and guideline development, eDNA could become an essential future component of the schistosomiasis control tool box needed to achieve the goal of elimination. SignificanceAccurate detection and delineation of schistosomiasis transmission sites will be vital in on-going efforts to control and ultimately eliminate one of the most neglected tropical parasitic diseases affecting more than 250 million people worldwide. Conventional methods to detect parasites in the environment are cumbersome and have low sensitivity. We therefore developed an environmental DNA (eDNA) based method for schistosome detection in aquatic environments. Aquatic eDNA showed higher sensitivity than conventional snail surveys. We conclude that eDNA is a promising non-invasive and sensitive tool for environmental surveillance of schistosomiasis transmission. As the efforts and aims to control the disease are transitioning towards complete transmission interruption, this could be the robust and cost-effective surveillance tool needed in the "end game" of schistosomiasis.

microbiology↗

bioRxiv2018

Moonlight: a tool for biological interpretation and driver genes discovery

Cancer is a complex and heterogeneous disease. It is crucial to identify the key driver genes and their role in cancer mechanisms with attention to different cancer stages, types or subtypes. Cancer driver genes are elusive and their discovery is complicated by the fact that the same gene can play a diverse role in different contexts. Key biological processes, such as cell proliferation and cell death, have been linked to cancer progression. Thus, in principle, they can be exploited to classify the cancer genes and unveil their role. Here, we present a new method, Moonlight, that exploit expression data to classify cancer genes. Moonlight relies on the integration of functional enrichment analysis, gene regulatory networks and upstream regulator analysis from expression data to score the importance of biological cancer-related processes taking into account either the inter- or intra-tumor heterogeneity. We then employed these scores to predict if each gene acts as a tumor suppressor gene (TSG) or as an oncogene (OCG). Our methodology also allow to predict genes with dual role, i.e. the moonlight genes (TSG in one cancer type or stage and OCG in another), as well as to elucidate the underlying biological processes. Availability: https://bioconductor.org/packages/MoonlightR & https://github.com/ibsquare/MoonlightR/

bioinformatics↗

bioRxiv2018

PARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation

PARP1 regulates the repair of DNA single strand breaks (SSBs) generated directly, or during base excision repair (BER). However, the role of PARP2 in these and other repair mechanisms is unknown. Here, we report a requirement for PARP2 in stabilising replication forks that encounter BER intermediates through Fbh1-dependent regulation of Rad51. Whilst PARP2 is dispensable for tolerance of cells to SSBs or homologous recombination dysfunction, it is redundant with PARP1 in BER. Therefore, combined disruption of PARP1 and PARP2 leads to defective BER, resulting in elevated levels of replication associated DNA damage due to an inability to stabilise Rad51 at damaged replication forks and prevent uncontrolled DNA resection. Together, our results demonstrate how PARP1 and PARP2 regulate two independent, but intrinsically linked aspects of DNA base damage tolerance by promoting BER directly, and through stabilising replication forks that encounter BER intermediates.

cell biology↗