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Biology subjects

Jacobson, P.

Publications and source records attributed to Jacobson, P..

6 recordsLinked to original sources

Navigating the salinity gradient: Individual variation in habitat use and migration of European eel revealed by otolith microchemistry

Knowledge regarding variation in habitat use among individuals is crucial for understanding population dynamics and for management and conservation measures. This is especially important for diadromous fishes that shift between habitats, being affected by external pressures and environmental change in different habitats over ontogeny. Herer, we assessed individual variation in habitat use of European eel along a salinity gradient, ranging from fully marine to freshwater in northern Europe, using otolith microchemistry data from >3600 eel together with established time-series segmentation and clustering methods. We show that eel display high degree of individual variation in habitat use. Assigned life-histories included coastal resident, freshwater resident, and coastal and freshwater habitat shifting individuals. Coastal resident eels were observed in a large range of salinities. Given the widespread occurrence of migration barriers in freshwater, it is unknown whether the coastal resident eel preferred that habitat, or if it was the only available habitat for them. Our findings nonetheless highlight the need to include coastal habitats when assessing population development and silver eel production of the critically endangered European eel.

ecology↗

Reduced size of larvae and small fish linked to warming and reduced prey density

Body size is a integrative trait that has declined across ecological assemblages in the last decades. Changes in body size of early life stages and small-bodied fish are driven by complex interactions between size-dependent mortality, and temperature- and food dependent growth, and can have consequences for recruitment to the adult stock and food availability to predators. While the mechanisms can be difficult to disentangle using observational data alone, simple indicators such as mean size can provide important information about ecosystem conditions as oceans rapidly change. Using 30 years of observations from the IBTS-MIK ichthyoplankton survey in Skagerrak and Kattegat in combination with sea surface temperature data, we investigated changes in the body size of early life stages and small-bodied fishes for 10 commercial and non-commercial species using geostatistical mixed models, and trends in prey density using generalized additive models. We found positive associations between chlorophyll-a concentration and length in 8 species (3 significant), and negative associations between temperature and length in 9 species (4 significant). Standardized indices of length revealed negative trends over time for all species since 2010, and all species were smaller in 2024 compared to 2000. The decline in size since 2010 varied between 30%-1%, with a mean of 14% and 9% for species predominantly found in Skagerrak and Kattegat, respectively. The trend of decreased body sizes since 2010 coincides with rapid declines in Calanus spp. -- a key prey predicted to decline in this area at the edge of their distribution area due to climate change. In Skagerrak it also coincides with a decline in the density of large copepods (> 0.25 mm). The synchronous declines in larval size across taxonomically diverse species experiencing different rates of exploitation suggest a common response to changing environmental conditions, which could have cascading effects throughout marine food webs.

ecology↗

Clone expansion of mutation-driven clonal hematopoiesis is associated with aging and metabolic dysfunction in individuals with obesity

AimsHaematopoietic clones caused by somatic mutations with [&ge;]2% variant allele frequency (VAF), known as clonal haematopoiesis of indeterminate potential (CHIP), increase with age and have been linked to risk of haematological malignancies and cardiovascular disease. Recent observations suggest that smaller clones are also associated with adverse clinical outcomes. Our aims were to determine the prevalence of clonal haematopoiesis driven by clones of variable sizes, and to examine the development of clones over time in relation to age and metabolic dysregulation over up to 20 years in individuals with obesity. Methods and ResultsWe used an ultrasensitive single-molecule molecular inversion probe sequencing assay to identify clonal haematopoiesis driver mutations (CHDMs) in blood samples from individuals with obesity from the Swedish Obese Subjects study. In a single-timepoint dataset with samples from 1050 individuals, we identified 273 candidate CHDMs in 216 individuals, with VAF ranging from 0.01% to 31.15% and CHDM prevalence and clone sizes increasing with age. Longitudinal analysis over 20 years in CHDM-positive samples from 40 individuals showed that small clones can grow over time and become CHIP. VAF increased on average by 7% (range -4% to 27%) per year. Rate of clone growth was positively associated with insulin resistance (R=0.40, P=0.025) and low circulating levels of high-density lipoprotein-cholesterol (HDL-C) (R=-0.68, P=1.74E-05). ConclusionOur results show that haematopoietic clones can be detected and monitored before they become CHIP and indicate that insulin resistance and low HDL-C, well-established cardiovascular risk factors, are associated with clonal expansion in individuals with obesity. Translational perspectivesClonal haematopoiesis-driver mutations are somatic mutations in haematopoietic stem cells that lead to clones detectable in peripheral blood. Haematopoietic clones with a variant allele frequency (VAF) [&ge;]2%, known as clonal haematopoiesis of indeterminate potential (CHIP), are recognized as an independent cardiovascular risk factor. Here, we show that smaller clones are prevalent, and also correlate with age. Our longitudinal observations in individuals with obesity over 20 years showed that more than half of all clone-positive individuals show growing clones and clones with VAF <2% can grow and become CHIP. Importantly, clone growth was accelerated in individuals with insulin resistance and low high-density lipoprotein-cholesterol (HDL-C). Translational outlook 1: Haematopoietic clones can be detected and monitored before they become CHIP. Translational outlook 2: The association between insulin resistance and low HDL-C with growth of haematopoietic clones opens the possibility that treatments improving metabolism, such as weight loss, may reduce growth of clones and thereby cardiovascular risk. One Sentence SummaryIn obesity, the growth rate of mutation-driven haematopoietic clones increased with insulin resistance and low HDL-C, both known risk factors for cardiovascular disease.

genomics↗

Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery

Development of accurate disease models and discovery of immune-modulating drugs is challenged by the immune systems highly interconnected and context-dependent nature. Here we apply deep-learning-driven analysis of cellular morphology to develop a scalable "phenomics" platform and demonstrate its ability to identify dose-dependent, high-dimensional relationships among and between immunomodulators, toxins, pathogens, genetic perturbations, and small and large molecules at scale. High-throughput screening on this platform demonstrates rapid identification and triage of hits for TGF-{beta}- and TNF--driven phenotypes. We deploy the platform to develop phenotypic models of active SARS-CoV-2 infection and of COVID-19-associated cytokine storm, surfacing compounds with demonstrated clinical benefit and identifying several new candidates for drug repurposing. The presented library of images, deep learning features, and compound screening data from immune profiling and COVID-19 screens serves as a deep resource for immune biology and cellular-model drug discovery with immediate impact on the COVID-19 pandemic.

immunology↗

Identification of potential treatments for COVID-19 through artificial intelligence-enabled phenomic analysis of human cells infected with SARS-CoV-2

To identify potential therapeutic stop-gaps for SARS-CoV-2, we evaluated a library of 1,670 approved and reference compounds in an unbiased, cellular image-based screen for their ability to suppress the broad impacts of the SARS-CoV-2 virus on phenomic profiles of human renal cortical epithelial cells using deep learning. In our assay, remdesivir is the only antiviral tested with strong efficacy, neither chloroquine nor hydroxychloroquine have any beneficial effect in this human cell model, and a small number of compounds not currently being pursued clinically for SARS-CoV-2 have efficacy. We observed weak but beneficial class effects of {beta}-blockers, mTOR/PI3K inhibitors and Vitamin D analogues and a mild amplification of the viral phenotype with {beta}-agonists.

systems biology↗

Non-rainfall moisture: a key driver of carbon flux from standing litter in arid, semiarid, and mesic grasslands

Models assume that rainfall is the major source of moisture driving decomposition. Non-rainfall moisture (NRM: high humidity, dew, and fog) can also induce standing litter decomposition, but there have been few standard measurements of NRM-mediated decompositions across sites, and no efforts to extrapolate the contribution of NRM to larger scales to assess whether this mechanism can improve model predictions. Here we show that NRM is an important, year-round source of moisture in grassland sites with contrasting moisture regimes using field measurements and modeling. We first characterized NRM frequency and measured NRM-mediated decomposition in sites on the extreme dry and wet end of grassland systems: at two sites in the Namib Desert, Namibia (hyperarid desert) and at one site in Iowa, USA (tallgrass prairie). NRM was frequent at all sites (85-99% of hours that litter was likely to be wet were attributed to NRM) and tended to occur in cool, high-humidity periods for several hours or more at a time. NRM also caused respiration of standing litter at all sites when litter became sufficiently wet (>5% for fine litter and >13% for coarse), and contributed to mass loss, even in the Namib West site that had almost no rain. When we modeled annual mass loss induced by NRM and rain, and extrapolated our characterization of NRM decomposition to a final site with intermediate rainfall (Sevilleta, New Mexico, semiarid grassland), we found that models driven by rainfall alone underestimated mass loss, while including NRM produced estimates within the range of observed mass loss. Together these findings suggest that NRM is an important missing component in quantitative and conceptual models of litter decomposition, but there is nuance involved in modeling NRM at larger scales. Specifically, temperature and physical features of the substrate emerge as factors that affect the common microbial response to litter wetting under NRM across grasslands sites, and require further study. Hourly humidity can provide an adequate proxy of NRM frequency, but site-specific calibration with litter wetness is needed to accurately attribute decomposition to periods when NRM wets litter. Greater recognition of NRM-driven decomposition and its interaction with other processes (e.g. photodegradation) is needed, especially since fog, dew, and humidity are likely to shift under future climates.\n\nManuscript highlightsO_LINon-rainfall moisture (NRM; humidity, fog, dew) induces decomposition in grasslands\nC_LIO_LINRM decomposition depends on substrate type, and occurs at colder times than rain\nC_LIO_LIIncluding NRM (instead of rain alone) improved predictions of litter decomposition\nC_LI

ecology↗