Biology subjects

Bergman, J.

Publications and source records attributed to Bergman, J..

18 recordsLinked to original sources

bioRxiv2026

A Curated Genome-Scale Nucleotide Diversity Panel of Non-Human Primates

BackgroundPrimates constitute one of the most phylogenetically and ecologically diverse Eutherian mammalian orders, with a central role in advancing our knowledge of human evolution, speciation processes and conservation biology. While thousands of whole-genome sequences have been generated across a multitude of primate taxa, discrepancies in data processing - particularly the lack of ploidy-aware variant calling in sex-linked regions - have limited the utility of existing datasets for large-scale comparative analyses. ResultsHere, we utilized publicly available short-read sequencing data of non-human primates, recently published primate genome assemblies and a ploidy-aware variant calling procedure to generate a genome-scale nucleotide diversity panel comprising 3,240 individuals from 269 species and 71 genera. To further facilitate cross-species comparisons, we generated a multiple-genome alignment of primate assemblies used for variant calling. ConclusionThis curated resource of non-human primate diversity provides a foundation for future research in primate evolutionary biology, speciation, and sex chromosome evolution (https://pure.au.dk/portal/en/datasets/primate-diversity-panel/).

genomics↗

bioRxiv2026

Comparison of the Distribution of Fitness Effects Across Primates

The distribution of fitness effects (DFE) of mutations is a key determinant of both the efficacy of natural selection and the genetic load of populations. It also provides an indirect summary of the underlying fitness landscape, so the extent to which the DFE is conserved across species is informative about the invariance of those landscapes. Here, we infer the DFE of amino-acid-changing mutations in 38 catarrhine subspecies using site-frequency spectrum (SFS)-based methods. We find that effective population size (Ne) is the dominant axis of cross-species variation in the population-scaled DFE for deleterious mutations, with the apparent clade-level clustering of estimates explained mainly by shared Ne rather than by clade-specific effects. A quantile-based test further shows that the underlying unscaled DFE does not vary significantly across species, so differences are consistent with Ne-rescaling of a single conserved DFE. Consistent with this, the deleterious (non-adaptive) substitution rate {omega}na declines significantly with Ne, reflecting more efficient purging of slightly deleterious mutations in larger populations. Turning to adaptive substitution, we find weaker, suggestive evidence that the adaptive rate {omega}a increases with Ne. These conclusions are robust to the choice of DFE parametrization, phylogenetic regression framework, the effect of GC-biased gene conversion, and ancestral misidentification. We also extend the DFE estimation procedure to relax the assumption of additive fitness effects, finding that dominance is only weakly identifiable from the SFS but has minimal impact on comparative DFE inference.

evolutionary biology↗

bioRxiv2026

Δ⁹-Tetrahydrocannabinol-induced enhancement of reward responsivity via mesocorticolimbic modulation in squirrel monkeys

{Delta}9-tetrahydrocannabinol (THC)-containing products are widely used recreationally, partly due to THCs ability to enhance the appetitive (i.e., rewarding) properties of diverse stimuli. However, the neural mechanisms through which THC modulates reward-related processing remain poorly understood. Here, we used a Pavlovian paradigm in adult squirrel monkeys (3males, 1female) to associate a visual conditioned stimulus (CS+) with appetitive food delivery. The modulatory effects of acute THC (1-10g/kg, i.m.) on behavioral and brain responses to CS+ were evaluated. Event-related functional MRI (fMRI) was employed to characterize the neural correlates of conditioned responding to the CS+, both in the absence and presence of THC treatment, with preconditioning scans serving as control. Behaviorally, THC (3g/kg) selectively enhanced conditioned responding to the CS+ without altering responses to the control stimulus (CS-) or increasing baseline consummatory responding, underscoring the specificity of THCs action on reward-associated processes. Consistently, fMRI analyses revealed that THC amplified CS+-evoked activation within mesocorticolimbic regions, including the anterior cingulate cortex (ACC), striatum, hippocampus, and substantia nigra-ventral tegmental area (SN-VTA), without affecting activity in visual and motor cortices. This finding underscores the selectivity of THCs neuromodulatory effects on reward-related circuitry. Independent of CS exposure, resting-state functional connectivity analyses indicate that THC enhanced mesocorticolimbic network integration, as evident in strengthened SN-VTA-centered connectivity with the ACC, striatum, and hippocampus. Collectively, these findings demonstrate that THC enhances the responses to appetitive stimuli, through selective modulation of mesocorticolimbic circuitry, highlighting the SN-VTA as a pivotal hub for cannabinoid-mediated regulation of incentive salience and motivational drive toward reward-associated stimuli. One-sentence summariesTHC enhances behavioral and neural responses to rewards through mesocorticolimbic modulation centered on the SN-VTA.

neuroscience↗

bioRxiv2025

Stone Age anthropogenic impacts to forest development in the interior Scandinavian Peninsula

Forest growth and development is a highly studied phenomenon in which humans have proven to be influential in shaping structure and composition. Delineating the long-term processes of human-environment interactions is crucial for understanding the history and trajectory of landscape formation and vegetation development. Yet, extensive knowledge of the ecological impacts of Stone Age anthropogenic activity is still lacking, particularly from Fennoscandian sites. A sediment core from South Mesna lake from the interior Scandinavian Peninsula was extracted to investigate the long-term evolutionary effects of human-environment interactions following deglaciation (c. 10,500 cal. BP) and initial colonization of the region. Analysis of the core involved microscopic/trace analytical methods, including geochemical analysis, stable isotope analysis, fecal biomarker analysis, and pollen analysis. The combined evidence demonstrates that anthropogenic impacts are prominent shapers of the ecological trajectory and landscape development of the region since the Early Neolithic (c. 5900 cal. BP), which has left a footprint on modern-day land cover. SignificanceAnthropogenic impacts on the environment have been observed to have had notable consequences on global and regional ecological trajectories and environmental development. Yet, how coupled human-environment interactions affect the long-term ecological complexion of boreal landscapes, such as those of the interior Scandinavian Peninsula, is not widely studied. This article presents evidence of early anthropogenic impacts to a forests ecology during the Holocene. Fecal biomarker and pollen analyses make it possible to provide micro-archaeological evidence of human activity and correlate it with noteworthy changes in forest structure. Our data points to a specific co-evolutionary forest development trajectory which is connected to millennial-scale human settlement patterns.

ecology↗

bioRxiv2024

Trade-offs beget trade-offs: Causal analysis of mammalian population dynamics

Survival and reproduction strategies in mammals are determined by trade-offs between life history traits. In turn, the unique configuration of traits that characterize mammalian species give rise to species-specific population dynamics. The dependence of population dynamics on life history has been primarily studied as the relationship between population density and size-related traits. With the recent accumulation of genomic data, the effective population size (Ne) over million-year timescales has become quantifiable for a large proportion of mammal species. Using phylogenetic path analysis, we compared the dependence of population density and Ne on eleven traits that characterize mammalian allometry, diet and reproduction. We found variable impacts of traits on the two metrics of population dynamics across different classifications of mammalian species. For example, we found a negative association between brain size and both population density and Ne overall, but brain size was positively associated with Ne in carnivorans. Dietary specialization had a negative effect on population density, especially in ungulates. Ne of ungulates and primates was strongly affected by time to maturity and weaning age, respectively, highlighting the difference in reproductive strategy between these orders. The relationship between Ne and adult mass showed a gradient in association strength from cold to warm biomes. Together, our findings demonstrate that trade-offs not only characterize life-history evolution, but also extend across different metrics of population dynamics and vary among species groups. This challenges the static nature of the "energetic equivalence" rule and has major implications for selecting appropriate metrics for species conservation and restoration strategies.

evolutionary biology↗

bioRxiv2024

Parallelism between phylogeny and ontogeny

Haeckels biogenetic law, or the recapitulation theory remains a controversial subject to this day. Currently, the modern version of biogenetic law is the hourglass model with its phylotypic period. Importantly, the hourglass model is nothing more than a model of development, and it does not provide any evidence that ontogeny recapitulates phylogeny. However, the hourglass model and biogenetic law are not mutually exclusive, and there are several examples of recapitulation-like processes observable after the phylotypic period of ontogeny. At the level of transcriptomics, all attempts to demonstrate recapitulation failed. Using a novel approach, combining transcriptomics with phylostratigraphy, we demonstrate that recapitulation, or parallelism between phylogeny and ontogeny, exists. We show that the mean indispensability of genes decreases for phylogenetically younger genes, as well as genes expressed during later stages of ontogeny. We also define the ontotypic period of phylogeny, an analog to the phylotypic period of ontogeny. Since it starts from the beginning of phylogeny, it is reasonable to hypothesize that recapitulation starts from the phylotypic period. We conclude that parallelism, or recapitulation, is explainable by the fact that genes that emerged later in phylogeny have tendencies to be expressed during later stages of ontogeny.

evolutionary biology↗

bioRxiv2023

Feasibility Study Utilizing NanoString Digital Spatial Profiling (DSP) Technology for Characterizing the Immune Microenvironment in Barrett's Esophagus FFPE Tissues

To date, characterization of the Barretts esophagus (BE) immune microenvironment in patients with known progression status to determine how the microenvironment may influence BE progression to esophageal adenocarcinoma (EAC) has been understudied, hindering both the biological understanding of progression and the development of novel diagnostics and therapies. Therefore, this studys aim was to determine if highly multiplex interrogation of the immune microenvironment can be performed on endoscopic formalin-fixed, paraffin-embedded (FFPE) samples utilizing the Nanostring GeoMx digital spatial profiling (GeoMx DSP) platform. We performed spatial proteomic analysis of 49 proteins expressed in the microenvironment and epithelial cells of histologically identical FFPE endoscopic biopsies from patients with non-dysplastic BE (NDBE) who later progressed to high-grade dysplasia (HGD) or EAC (N=7) or from patients who after at least 5 years follow up did not (N=8). In addition, we performed RNA analysis of 1,812 cancer related transcripts on a series of three endoscopic mucosal resections containing regions of normal tissue, BE, dysplasia (DYS), and EAC. Our primary goal was to determine feasibility of this approach and begin to identify the types of specific immune cell populations that may mediate the progression of pre-neoplastic BE to EAC. Spatial proteomic and transcriptomic profiling with GeoMx DSP showed reasonable quality metrics and detected expected differences between epithelium and stroma. Several proteins were found to have increased expression within non-dysplastic BE biopsies from progressors compared to non-progressors, suggesting further studies on the BE microenvironment are warranted. SummaryNew biological insights into the stepwise development and progression of esophageal adenocarcinoma (EAC) from Barretts esophagus (BE) are imperative to develop tailored approaches for early detection and optimal clinical management of the disease. This study aimed to determine the feasibility to spatially profile stromal and immunologic properties that accompany malignant transformation of BE to EAC in formalin-fixed, paraffin-embedded (FFPE) tissues. NanoStrings Digital Spatial Profiling (DSP) technology can detect and quantify protein and RNA transcripts in a highly multiplexed manner with spatial resolution, within specific regions of interest on FFPE tissue. Here, we performed a pilot study using the Nanostring GeoMx DSP, for measurement of protein and ribonucleic acid (RNA) expression on a series of FFPE slides from endoscopic biopsies and endoscopic mucosal resections (EMR) of BE. We compare a small series of biopsies of non-dysplastic BE (NDBE) from patients who progressed to more advanced disease to patients with NBDE who did not progress and then perform RNA profiling on EMRs with a range of histologic diagnoses.

cancer biology↗

bioRxiv2023

Inference of Genomic Landscapes using Ordered Hidden Markov Models with Emission Densities (oHMMed)

BackgroundGenomes are inherently inhomogeneous, with features such as base composition, recombination, gene density, and gene expression varying along chromosomes. Evolutionary, biological, and biomedical analyses aim to quantify this variation, account for it during inference procedures, and ultimately determine the causal processes behind it. Since sequential observations along chromosomes are not independent, it is unsurprising that autocorrelation patterns have been observed e.g., in human base composition. In this article, we develop a class of Hidden Markov Models (HMMs) called oHMMed (ordered HMM with emission densities, the corresponding R package of the same name is available on CRAN): They identify the number of comparably homogeneous regions within autocorrelated observed sequences. These are modelled as discrete hidden states; the observed data points are realisations of continuous probability distributions with state-specific means that enable ordering of these distributions. The observed sequence is labelled according to the hidden states, permitting only neighbouring states that are also neighbours within the ordering of their associated distributions. The parameters that characterise these state-specific distributions are inferred. ResultsWe apply our oHMMed algorithms to the proportion of G and C bases (modelled as a mixture of normal distributions) and the number of genes (modelled as a mixture of poisson-gamma distributions) in windows along the human, mouse, and fruit fly genomes. This results in a partitioning of the genomes into regions by statistically distinguishable averages of these features, and in a characterisation of their continuous patterns of variation. In regard to the genomic G and C proportion, this latter result distinguishes oHMMed from segmentation algorithms based in isochore or compositional domain theory. We further use oHMMed to conduct a detailed analysis of variation of chromatin accessibility (ATAC-seq) and epigenetic markers H3K27ac and H3K27me3 (modelled as a mixture of poisson-gamma distributions) along the human chromosome 1 and their correlations. ConclusionsOur algorithms provide a biologically assumption-free approach to characterising genomic landscapes shaped by continuous, autocorrelated patterns of variation. Despite this, the resulting genome segmentation enables extraction of compositionally distinct regions for further downstream analyses.

bioinformatics↗

bioRxiv2023

Single nucleus transcriptomics of human and monkey striatum implicates DNA damage, neuroinflammation, and neurodegeneration signaling in opioid use disorder

The striatum in the brain is involved in various behavioral functions, including reward, and disease processes, such as opioid use disorder (OUD). Further understanding of the role of striatal subregions in reward behaviors and their potential associations with OUD requires molecular identification of specific striatal cell types in human brain. The human striatum contains subregions based on different anatomical, functional, and physiological properties, with the dorsal striatum further divided into caudate and putamen. Both caudate and putamen are involved in altered reward processing, formation of habits, and development of negative affect states associated with OUD. Using single nuclei RNA-sequencing of human postmortem caudate and putamen, we identified canonical neuronal cell types in striatum (e.g., dopamine receptor 1 or 2 expressing neurons, D1 or D2) and less abundant subpopulations, including D1/D2-hybrid neurons and multiple classes of interneurons. By comparing unaffected subjects to subjects with OUD, we found neuronal-specific differences in pathways related to neurodegeneration, interferon response, and DNA damage. DNA damage markers were also elevated in striatal neurons of rhesus macaques following chronic opioid administration. We also identified sex-dependent differences in the expression of stress-induced transcripts among astrocytes and oligodendrocytes from female subjects with OUD. Thus, we describe striatal cell types and leverage these data to gain insights into molecular alterations in human striatum associated with opioid addiction.

neuroscience↗

bioRxiv2023

The landscape of tolerated genetic variation in humans and primates

Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole genome sequencing data for 809 individuals from 233 primate species, and identified 4.3 million common protein-altering variants with orthologs in human. We show that these variants can be inferred to have non-deleterious effects in human based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases. One Sentence SummaryDeep learning classifier trained on 4.3 million common primate missense variants predicts variant pathogenicity in humans.

genomics↗

bioRxiv2023

A global catalog of whole-genome diversity from 233 primate species

The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology, and is urgent given severe threats these species are facing. Here, we present high coverage whole-genome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human-specific. This study will open a wide range of research avenues for future primate genomic research. One-Sentence SummaryThe whole genome sequences of 233 primate species provide insight into the determinants of genetic diversity, phylogenomics, and human uniqueness.

genomics↗

bioRxiv2023

Resting state networks of awake adolescent and adult squirrel monkeys using ultra-high field (9.4T) functional magnetic resonance imaging

Resting state networks (RSNs) are increasingly forwarded as candidate biomarkers for neuropsychiatric disorders. Such biomarkers may provide objective measures for evaluating novel therapeutic interventions in nonhuman primates often used in translational neuroimaging research. This study aimed to characterize the RSNs of awake squirrel monkeys and compare the characteristics of those networks in adolescent and adult subjects. Twenty-seven squirrel monkeys (n=12 adolescents [6 male/6 female] [~]2.5 years and n=15 adults [7 male/8 female] [~]9.5 years) were gradually acclimated to awake scanning procedures; whole-brain fMRI images were acquired with a 9.4 Tesla scanner. Group level independent component (IC) analysis (30 ICs) with dual regression was used to detect and compare RSNs. Twenty ICs corresponding to physiologically meaningful networks representing a range of neural functions, including motor, sensory, reward (e.g., basal ganglia), and cognitive processes were identified in both adolescent and adult monkeys. Significant age-related differences between the adult and adolescent subjects (adult > adolescent) were found in two networks of interest: (1) the right upper occipital region with an OFC IC and (2) the left temporal cortex, bilateral visual areas, and cerebellum with the cingulate IC. These results demonstrate that squirrel monkey RSNs are stable and consistent with RSNs previously identified in humans, rodents, and other nonhuman primate species. These data also identify several networks in adolescence that are conserved and others that may change into adulthood. Significance StatementFunctional magnetic resonance imaging procedures have revealed important information about how the brain is modified by experimental manipulations, disease states, and aging throughout the lifespan. Preclinical neuroimaging, especially in nonhuman primates, has become a frequently used means to answer targeted questions related to brain resting-state functional connectivity. The present study characterized resting state networks (RSNs) in adult and adolescent squirrel monkeys; twenty RSNs corresponding to networks representing a range of neural functions were identified. The RSNs identified here can be utilized in future studies examining the effects of experimental manipulations on brain connectivity in squirrel monkeys. These data also may be useful for comparative analysis with other primate species to provide an evolutionary perspective for understanding brain function and organization.

neuroscience↗

bioRxiv2022

Traditional phylogenetic models are insensitive to variations in the effective population size

A substitution represents the emergence and fixation of an allele in a population or species and is the fundamental event from which phylogenetic models of sequence evolution are devised. Because of the increasing availability of genomic sequences, we are now able to take advantage of intraspecific variability when reconstructing the tree of life. As a result, substitutions can be more realistically modeled as the product of mutation, selection, and genetic drift. However, it is still unclear whether this increased complexity affects our measures of evolutionary times and rates. This study seeks to answer this question by contrasting the traditional substitution model with a population genetic equivalent using data from 4385 individuals distributed across 179 populations and representing 17 species of animals, plants, and fungi. We found that when the population genetics dynamic is modeled via the substitution rates, the evolutionary times and rates of the two models are well correlated, suggesting that the phylogenetic model is able to capture the time and pace of its population counterpart. However, a closer inspection of this result showed that the traditional models largely ignore the effect of the effective population size, even when it is explicitly accounted for in the substitution rates. Our findings suggest that superimposing population-genetics results on the substitution rates is an effective strategy to study mutation and selection biases, while other data sources (e.g., life history traits or polymorphisms) may need to be additionally integrated to make the traditional substitution models sensitive to the impact of genetic drift. When combined with the known effect of ancestral population size on generating phylogenomic incongruence due to incomplete lineage sorting, our findings provide further evidence that unaccounted-for variations in the effective population size may be one of the primary causes of errors in phylogenetic analyses at shorter time scales.

evolutionary biology↗

bioRxiv2022

Worldwide late-Quaternary population declines in extant megafauna are due to Homo sapiens rather than climate

The worldwide loss of large animal species over the past 100,000 years is evident from the fossil record, with climate and human impact as the most likely causes of megafauna extinctions. To help distinguish between these two scenarios, we analysed whole-genome sequence data of 142 species to infer their population size histories during the Quaternary. We modelled differences in population dynamics among species using ecological factors, paleoclimate and human presence as covariates. We report a significant population decline towards the present time in more than 90% of species, with larger megafauna experiencing the strongest decline. We find that population decline became ubiquitous approximately 100,000 years ago, with the majority of species experiencing their lowest population sizes during this period. We assessed the relative impact of climate fluctuations and human presence on megafauna dynamics and found that climate has limited explanatory power for late-Quaternary shifts in megafauna population sizes, which are largely explained by Homo sapiens arrival times. As a consequence of megafauna decline, total biomass and metabolic input provided by these species has drastically reduced to less than 25% compared to 100,000 years ago. These observations imply that the worldwide expansion of H. sapiens caused a major restructuring of ecosystems at global scale.

evolutionary biology↗

bioRxiv2021

Evolutionary dynamics of pseudoautosomal region 1 in humans and great apes

The pseudoautosomal region 1 (PAR1) is a 2.7 Mb telomeric region of human sex chromosomes. As the largest point of contact between the X and Y, PAR1 has a crucial role in ensuring proper segregation of sex chromosomes during male meiosis, exposing it to extreme recombination and associated mutational processes. We investigate PAR1 evolution using population genomic datasets of extant humans, eight populations of great apes and two archaic human genome sequences. We find that the PAR1 sequence is closer to nucleotide equilibrium than autosomal telomeric sequences. We detect a difference between long-term substitution patterns and extant diversity in PAR1 that is mainly driven by the conflict between strong mutation and recombination-associated fixation bias at CpG sites. Additionally, we detect excess C[->]G mutations in PAR1 of all great ape species, specific to the mutagenic effect of male recombination. Analysis of differences between frequencies of alleles segregating in females and males provided no evidence for sexually antagonistic selection in this region. Furthermore, despite recent evidence for Y chromosome introgression from humans into Neanderthals, we find that the Neanderthal PAR1 retained similarity to the Denisovan sequence, as is the case for the X chromosome and the autosomes. Lastly, we study repeat content and double-strand break hotspot regions in PAR1 and find that they may play roles in ensuring the obligate X-Y recombination event during male meiosis. Our study provides an unprecedented quantification of population genetic forces and insight into evolutionary processes governing PAR1 biology.

evolutionary biology↗

bioRxiv2020

Population dynamics of GC-changing mutations in humans and great apes

BackgroundThe nucleotide composition of the genome is a balance between origin and fixation rates of different mutations. For example, it is well-known that transitions occur more frequently than transversions, particularly at CpG sites. Differences in fixation rates of mutation types are less explored. Specifically, recombination-associated GC-biased gene conversion (gBGC) may differentially impact GC-changing mutations, due to differences in their genomic distributions and efficiency of mismatch repair mechanisms. Given that recombination evolves rapidly across species, we explore gBGC of different mutation types across human populations and among great ape species. ResultsWe report a stronger correlation between GC frequency and recombination for transitions than for transversions. Notably, CpG transitions are most strongly affected by gBGC. We show that the strength of gBGC differs for transitions and transversions but that its overall strength is positively correlated with effective population sizes of human populations and great ape species, with some notable exceptions, such as a stronger effect of gBGC on non-CpG transitions in populations of European descent. We study the dependence of gBGC dynamics on flanking nucleotides and show that some mutation types evolve in opposition to the gBGC expectation, likely due to hypermutability of specific nucleotide contexts. ConclusionsDifferences in GC-biased gene conversion are evident between different mutation types, and dependent on sex-specific recombination, population size and flanking nucleotide context. Our results therefore highlight the importance of different gBGC dynamics experienced by GC-changing mutations and their impact on nucleotide composition evolution.

evolutionary biology↗

bioRxiv2019

Optimization of 3D bioprinting of human neuroblastoma cells using sodium alginate hydrogel

There are many parameters in extrusion-based three-dimensional (3D) bioprinting of different materials that require fine-tuning to obtain the optimal print resolution and cell viability. To standardize this process, methods such as parameter optimization index (POI) have been introduced. The POI aims at pinpointing the optimal printing speed and pressure to achieve the highest accuracy keeping theoretical shear stress low. Here we applied the POI to optimize the process of 3D bioprinting human neuroblastoma cell-laden 2% sodium alginate (SA) hydrogel using freeform reversible embedding of suspended hydrogels (FRESH). Our results demonstrate a notable difference between optimal parameters for printing 2% SA with and without cells in the hydrogel. We also detected a significant influence of long-term cell culture on the printed constructs. This observation suggests that the POI has to be evaluated in the perspective of the final application. When taking these conditions into consideration, we could define a set of parameters that resulted in good quality prints maintaining high neuroblastoma cell viability (83% viable cells) during 7 days of cell culture using 2% SA and FRESH bioprinting. These results can be further used to manufacture neuroblastoma in vitro 3D culture systems to be used for cancer research.

bioengineering↗

bioRxiv2018

Does Adaptive Protein Evolution Proceed by Large or Small Steps at the Amino Acid Level?

A longstanding question in evolutionary biology is the relative contribution of large and small effect mutations to the adaptive process. We have investigated this question in proteins by estimating the rate of adaptive evolution between all pairs of amino acids separated by one mutational step using a McDonald-Kreitman type approach and genome-wide data from several Drosophila species. We find that the rate of adaptive evolution is higher amongst amino acids that are more similar. This is partly due to the fact that the proportion of mutations that are adaptive is higher amongst more similar amino acids. We also find that the rate of neutral evolution between amino acids is higher amongst similar amino acids. Overall our results suggest that both the adaptive and non-adaptive evolution of proteins is dominated by substitutions between amino acids that are more similar.

evolutionary biology↗