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Biology subjects

Anderson, N.

Publications and source records attributed to Anderson, N..

At least 19 recordsLinked to original sources

Selection for propagule formation in prebiotic chemical ecosystems

Biological individuals on Earth today are cellular, but the simplest cells are too complex to have arisen spontaneously. We explore the hypothesis that the emergence of biological individuality might have been driven by selection for different molecules to move through space together by forming a propagule. We predicted that propagule formation will be advantageous to an autocatalytic system primarily when 1) sites supporting autocatalysis are distantly spaced and 2) the environment undergoes periodic disturbances. We tested this hypothesis using computational reaction-diffusion models of surface-catalyzed autocatalytic systems in patchy, disturbance-prone environments. We considered two competing autocatalytic cycles, each composed of mutualistic subcycles, one of which diverts flux to the production of propagules. Our analysis shows that propagules tend to be detrimental in well-mixed environments or environments where viable surfaces are close enough together to be reliably seeded through single-species dispersal. However, propagule formation is advantageous when long stretches of empty space must be crossed to reach new resources and/or when environmental disturbances are frequent. These findings suggest spatial structure can selectively favor reliable forms of codispersal. Evolution in response to this mechanism could potentially explain the emergence of vesicles that transported many autocatalytic species and eventually became independent protocells.

evolutionary biology↗

A sex-specific regulator expands the embryonic ocular field to generate a novel visual system

Morphological novelties often emerge through the redeployment of conserved developmental programs, but how such programs become activated in new developmental contexts remains poorly understood. We investigated the evolutionary origin of the turbanate eyes (TurbEyes) of mayflies, a male-specific additional visual system. Using single-cell transcriptomics, chromatin accessibility profiling and functional genetics, we show that this novelty develops through deployment of the ancestral retinal determination gene network (RDGN). We identify a novel, male-specific paralog of the sex determination transcription factor Doublesex, DsxM, that regulates the eye-specification gene eyeless/Pax6 and promotes the expansion of the embryonic ocular field. Functional assays impairing dsxM activity reduce this male-specific expansion and causes defects in TurbEye development. Our findings reveal a developmental mechanism by which a sex-specific regulator generates a new developmental territory, enabling the spatial redeployment of a conserved developmental program and to generate a novel male-specific visual system.

evolutionary biology↗

Repurposing antiviral drugs as a new avenue for Klebsiella pneumoniae decolonization

Klebsiella pneumoniae (Kp) is a common antibiotic-resistant pathogen that colonizes the gastrointestinal tract and can disseminate to peripheral sites, causing a range of infections including bacteremia, urinary tract infections, and pneumonia. Intestinal colonization with Kp is a risk factor for subsequent infection, as the colonizing strain frequently corresponds to the infecting isolate. Accordingly, targeting Kp prior to dissemination at the site of colonization through decolonization strategies offers a promising approach to mitigate infection risk. In this study, we evaluated the repurposing of existing drugs with previously uncharacterized antibacterial activity as candidates for Kp decolonization. To this end, we screened an antiviral compound library for their activity against Kp. We identified and validated six compounds with previously uncharacterized activity against Kp. Then, we screened a library of clinical Kp strains against a subset of these compounds and found that their activity was strain-specific to degrees that differed based on the compound. Finally, we tested the activity of these compounds in conditions relevant to the human gut. We determined the activity of these candidates was dependent on biological context. Collectively, these findings support further investigation of antiviral drugs as potential gut decolonization therapies for Kp.

microbiology↗

Embryonic origin of cancer in newborn twins

Studying monozygotic twins who present with identical cancers informs on the developmental origins of childhood tumours. Here, we performed whole genome sequencing on multiple tumour, normal, and placental samples to reconstruct the phylogeny of a soft tissue cancer that spread in utero between monozygotic twins. This generalisable and scalable approach allows us to dissect the earliest stages of twinning, revealing unexpected asymmetrical contributions of embryonic lineages to the placenta and each twin.

cancer biology↗

hENT Inhibition Prevents Pyrimidine-Driven Resistance to DHODH Inhibition in Malignant Rhabdoid Tumors

Extracranial malignant rhabdoid tumors (ecMRTs) are aggressive pediatric cancers characterized by mutations in genes encoding members of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, with limited effective treatment options. Metabolic reprogramming, including nucleotide biosynthesis, is a hallmark of cancer that represents a potential therapeutic vulnerability. Previously, we demonstrated that inhibition of the de novo pyrimidine synthesis enzyme dihydroorotate dehydrogenase (DHODH) represents a promising treatment strategy for rhabdoid tumors, including ecMRTs and atypical teratoid/rhabdoid tumors (AT/RTs). Using patient-derived tumoroid models, we now extend these findings by showing that another SWI/SNF-deficient pediatric cancer, small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is also sensitive to DHODH inhibition. Gene expression analyses further confirmed that SCCOHT and AT/RT, like ecMRT, exhibit elevated expression of de novo nucleotide synthesis genes. To determine whether metabolic features of the tumor microenvironment (TME) influence DHODH inhibitor (DHODHi) response, we profiled plasma and tumor interstitial fluid from orthotopic ecMRT-bearing mice and found that the TME was markedly enriched in nucleosides and nucleobases. Supplementation of standard culture media with these nucleosides demonstrated that pyrimidines, but not purines, can rescue ecMRT cells from DHODHi-induced growth inhibition via activation of the pyrimidine salvage pathway. This resistance mechanism was effectively reversed by co-treatment with human equilibrative nucleoside transporter (hENT) inhibitors, enhancing DHODHi sensitivity in ecMRTs. Collectively, these findings reveal a conserved metabolic vulnerability across SWI/SNF-deficient pediatric cancers and emphasize the critical importance of modeling tumor metabolism under physiologically relevant conditions to accurately identify metabolism-targeted therapeutic strategies for these currently lethal pediatric cancer types.

cancer biology↗

Evidence for an ancient master sex determination gene in Hymenoptera

The vast majority of Hymenopterans determine sex by haplodiploidy, in which males and females develop from haploid unfertilized and diploid fertilized eggs, respectively. At the molecular level, the majority of Hymenoptera are thought to determine sex by so-called Complementary Sex Determination (CSD). Under CSD, sex is determined by the feminizing effects of one or more allele-rich loci, in which the feminizing function is imparted by the interactions of functionally distinct alleles. Because of high allelic diversity, most diploids are heterozygous and develop as females, whereas haploid individuals develop as males, as do rare homozygous diploids. Despite diverse empirical results suggesting that CSD is widespread in Hymenopterans, and substantial theoretical and empirical study of the consequences of CSD, the molecular biology of CSD has received little attention outside of the honeybee, Apis mellifera. Available evidence provides support for divergent perspectives ranging from a single (nearly) universally-conserved CSD locus or a pattern dominated by evolutionary turnover with different genes serving as the CSD gene(s) in different lineages. Recently, a novel non-coding RNA gene named ANTSR was shown to serve as a CSD gene in different ant lineages, and the authors suggested that ANTSR might serve as a more broadly-conserved CSD gene. To assess the role of ANTSR role in CSD across diverse Hymenoptera, we studied syntenic conservation and polymorphism patterns in the broad ANTSR locus, genome-wide sequence from available male and female diploid Formica ants, and data from a sibling cross for Bombus terrestris. We find evidence that ANTSR is a conserved CSD gene across diverse Aculeata, the largest group of Hymenoptera, and provide preliminary evidence that Formica may have multiple CSD loci including ANTSR.

genetics↗

Vnd and En are expressed in orthogonal stripes and act in a brief competence window to combinatorially specify NB7-1 and its early lineage

Understanding how neuronal diversity is generated is a major goal of neuroscience. Here we characterize the first step in generating neuronal diversity in the Drosophila embryo: spatial transcription factors (STFs) expressed in orthogonal rows and columns of neural progenitors. These factors give spatial identity to neural progenitors (neuroblasts, NBs), and are highly conserved in mammals. Here we investigate the roles of Engrailed (En+; posterior row) and Vnd+ (medial column) in specifying the well-characterized progenitor: neuroblast 7-1 (NB7-1). We show that NB7-1 is located at the intersection of Vnd and En, and we identify NB7-1 using a newly characterized gene, fd4, that we show is specifically expressed in NB7-1 and its progeny, giving us a specific assay for NB7-1 identity. We show that En and Vnd are both required for Fd4 expression, and that Vnd and En co-expression is sufficient to induce ectopic Fd4 expression in other NBs and their lineages. Finally, we show that NBs gradually lose competence to respond to En or Vnd. We conclude that En and Vnd are STFs that act combinatorially to specify the identity of an individual progenitor, NB7-1.

developmental biology↗

Uncovering Fusarium species diversity, distribution and pathogenicity associated with cotton and corn fields in recently expanded cotton-growing areas of the Northern High Plains of Texas

The recent expansion of cotton acreage in the Northern High Plains of Texas has raised concerns about the occurrence of a diverse Fusarium community, particularly Fusarium oxysporum f. sp. vasinfectum race 4. We investigated the diversity, distribution, and pathogenicity of Fusarium species in soil samples collected from 26 cotton-corn rotation fields across 10 counties. A total of nine Fusarium species were isolated: F. incarnatum, F. equiseti, F. solani, F. verticillioides, F. proliferatum, F. clavum, F. oxysporum, F. flocciferum, and one unidentified Fusarium sp. The highest species diversity (five species) was observed in Sherman County. Fusarium solani was the most frequently isolated species (39%) across all counties, followed by F. equiseti (22%), while F. flocciferum was the least frequently isolated species (2%). Greenhouse pathogenicity assays showed F. incarnatum caused significantly higher disease severity relative to non-inoculated control on aerial parts of cotton (P=0.0137), while Fusarium flocciferum, F. proliferatum, and F. clavum caused significantly higher disease severity relative to non-inoculated control on roots (P=0.01, P=0.01, P=0.02, respectively). On corn, differences in disease severity were not statistically significant (P>0.05). Fusarium isolates were recovered from both symptomatic and asymptomatic roots following pathogenicity trials, suggesting endophytic colonization. This study revealed a complex Fusarium community capable of cross-infecting cotton and corn, with implications for regional disease management. The absence of Fusarium oxysporum f. sp. vasinfectum race 4 indicates it may not yet have been introduced into the Northern High Plains; however, continued surveillance is warranted given its detection in New Mexico and adjacent counties in Texas.

ecology↗

Olduvai domain expression downregulates mitochondrial pathways: implications for human brain evolution and neoteny

Olduvai (formerly DUF1220) protein domains, encoded by the NBPF gene family, have undergone the greatest human lineage-specific copy-number expansion of any coding sequence in the genome and strongly correlate with brain size and neuron number across primates. Here we show that Olduvai domains act in a dosage-dependent manner to suppress mitochondrial metabolism. Transcriptomic, proteomic, and live-cell imaging analyses of cells overexpressing NBPF1 (which encodes seven Olduvai domains) reveal pronounced downregulation of mitochondrial pathways, including electron transport chain components and NADH dehydrogenase activity, as well as reduced mitochondrial abundance. By limiting energy availability, this suppression delays cellular maturation and developmental timing. We propose that the resulting prolongation of neurogenesis increases neuron production, providing a mechanistic link between Olduvai copy number expansion and the evolutionary enlargement of the human brain. This dosage-sensitive mitochondrial regulation may also contribute to broader neotenic features of human development, offering a unifying molecular mechanism for brain expansion and the neotenic traits that distinguish humans from other primates.

genomics↗

Individual variability in neural representations of mind-wandering

Mind-wandering is a frequent, daily mental activity, experienced in unique ways in each person. Yet neuroimaging evidence relating mind-wandering to brain activity, for example in the default mode network (DMN), has relied on population-rather than individual-based inferences due to limited within-individual sampling. Here, three densely-sampled individuals each reported hundreds of mind-wandering episodes while undergoing multi-session functional magnetic resonance imaging. We found reliable associations between mind-wandering and DMN activation when estimating brain networks within individuals using precision functional mapping. However, the timing of spontaneous DMN activity relative to subjective reports, and the networks beyond DMN that were activated and deactivated during mind-wandering, were distinct across individuals. Connectome-based predictive modeling further revealed idiosyncratic, whole-brain functional connectivity patterns that consistently predicted mind-wandering within individuals but did not fully generalize across individuals. Predictive models of mind-wandering and attention that were derived from larger-scale neuroimaging datasets largely failed when applied to densely-sampled individuals, further highlighting the need for personalized models. Our work offers novel evidence for both conserved and variable neural representations of self-reported mind-wandering in different individuals. The previously-unrecognized inter-individual variations reported here underscore the broader scientific value and potential clinical utility of idiographic approaches to brain-experience associations.

neuroscience↗

Do organisms need an impact factor? Citations of key biological resources including model organisms reveal usage patterns and impact.

Research resources like transgenic animals and antibodies are the workhorses of biomedicine, enabling investigators to relatively easily study specific disease conditions. As key biological resources, transgenic animals and antibodies are often validated, maintained, and distributed from university based stock centers. As these centers heavily rely largely on grant funding, it is critical that they are cited by investigators so that usage can be tracked. However, unlike systems for tracking the impact of papers, the conventions and systems for tracking key resource usage and impact lag behind. Previous studies have shown that about 50% of the resources are not findable, making the studies they are supporting irreproducible, but also makes tracking resources difficult. The RRID project is filling this gap by working with journals and resource providers to improve citation practices and to track the usage of these key resources. Here, we reviewed 10 years of citation practices for five university based stock centers, characterizing each reference into two broad categories: findable (authors could use the RRID, stock number, or full name) and not findable (authors could use a nickname or a common name that is not unique to the resource). The data revealed that when stock centers asked their communities to cite resources by RRID, in addition to helping stock centers more easily track resource usage by increasing the number of RRID papers, authors shifted from citing resources predominantly by nickname ([~]50% of the time) to citing them by one of the findable categories ([~]85%) in a matter of several years. In the case of one stock center, the MMRRC, the improvement in findability is also associated with improvements in the adherence to NIH rigor criteria, as determined by a significant increase in the Rigor and Transparency Index for studies using MMRRC mice. From this data, it was not possible to determine whether outreach to authors or changes to stock center websites drove better citation practices, but findability of research resources and rigor adherence was improved.

bioinformatics↗

Social cognitive regions of human association cortex are selectively connected to the amygdala

Reasoning about someones thoughts and intentions - i.e., forming a theory of mind - is an important aspect of social cognition that relies on association areas of the brain that have expanded disproportionately in the human lineage. We recently showed that these association zones comprise parallel distributed networks that, despite occupying adjacent and interdigitated regions, serve dissociable functions. One network is selectively recruited by theory of mind processes. What circuit properties differentiate these parallel networks? Here, we show that social cognitive association areas are intrinsically and selectively connected to regions of the anterior medial temporal lobe that are implicated in emotional learning and social behaviors, including the amygdala at or near the basolateral complex and medial nucleus. The results suggest that social cognitive functions emerge through coordinated activity between amygdala circuits and a distributed association network, and indicate the medial nucleus may play an important role in social cognition in humans.

neuroscience↗

Situating the parietal memory network in the context of multiple parallel distributed networks using high-resolution functional connectivity

A principle of brain organization is that networks serving higher cognitive functions are widely distributed across the brain. One exception has been the parietal memory network (PMN), which plays a role in recognition memory but is often defined as being restricted to posteromedial association cortex. We hypothesized that high-resolution estimates of the PMN would reveal small regions that had been missed by prior approaches. High-field 7T functional magnetic resonance imaging (fMRI) data from extensively sampled participants was used to define the PMN within individuals. The PMN consistently extended beyond the core posteromedial set to include regions in the inferior parietal lobule; rostral, dorsal, medial, and ventromedial prefrontal cortex; the anterior insula; and ramus marginalis of the cingulate sulcus. The results suggest that, when fine-scale anatomy is considered, the PMN matches the expected distributed architecture of other association networks, reinforcing that parallel distributed networks are an organizing principle of association cortex.

neuroscience↗

Clinically-relevant treatment of PDX models reveals patterns of neuroblastoma chemoresistance

Chemotherapy resistance and relapses are common in high-risk neuroblastoma (NB), an aggressive pediatric solid tumor of the sympathetic nervous system. Here, we developed a clinically-relevant in vivo treatment protocol mimicking the first line five-chemotherapy treatment regimen of high-risk NB and applied this protocol to mice with MYCN-amplified NB patient-derived xenografts (PDXs). Genomic and transcriptomic analyses were used to reveal the genetic and non-genetic mechanisms involved in NB chemoresistance. We observed convergent and parallel evolution of key NB genetic aberrations over time. Intrinsic resistance to chemotherapy was associated with high genetic diversity and an embryonic phenotype. Relapsed NB PDX tumors with acquired resistance showed an immature mesenchymal-like phenotype resembling multipotent Schwann cell precursors that are found in the adrenal gland. NBs with a successful treatment response presented a lineage-committed adrenergic phenotype similar to normal neuroblasts, reduced cell cycle gene expression, and negative regulation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) cascade. NB organoids established from relapsed PDX tumors retained drug resistance, tumorigenicity, and transcriptional cell states ex vivo. This work sheds light on mechanisms involved in NB chemotherapy response in vivo and ex vivo using a clinically-relevant protocol, and emphasizes the importance of transcriptional cell states in treatment response. Detailed characterization of resistance mechanisms is essential for the development of novel treatment strategies in non-responsive or relapsed high-risk NB. One Sentence SummaryCOJEC chemotherapy treatment of neuroblastoma PDX models uncovers patterns of transcriptional plasticity and chemoresistance.

cancer biology↗

Proteolytic Activation of Human-specific Olduvai Domains by the Furin Protease

Olduvai protein domains (formerly DUF1220) show the greatest human-specific increase in copy number of any coding region in the genome and are highly correlated with human brain evolution and cognitive disease. The majority of human copies are found within four NBPF genes organized in a variable number of a tandemly arranged three-domain blocks called Olduvai triplets. Here we show that these human-specific Olduvai domains are posttranslationally processed by the furin protease, with a cleavage site occurring once at each triplet. These findings suggest that all expanded human-specific NBPF genes encode proproteins consisting of many independent Olduvai triplet proteins which are activated by furin processing. The exceptional correlation of Olduvai copy number and brain size taken together with our new furin data, indicates the ultimate target of selection was a rapid increase in dosage of autonomously functioning Olduvai triplet proteins, and that these proteins are the primary active agent underlying Olduvais role in human brain expansion.

evolutionary biology↗

Predicting Moisture Content During Maize Nixtamalization Using Machine Learning with NIR Spectroscopy

Lack of high throughput phenotyping systems for determining moisture content during the maize nixtamalization cooking process has led to difficulty in breeding for this trait. This study provides a high throughput, quantitative measure of kernel moisture content during nixtamalization based on NIR scanning of uncooked maize kernels. Machine learning was utilized to develop models based on the combination of NIR spectra and moisture content determined from a scaled-down benchtop cook method. A linear support vector machine (SVM) model with a Spearmans rank correlation coefficient of 0.852 between wet lab and predicted values was developed from 100 diverse temperate genotypes grown in replicate across two environments. This model was applied to NIR data from 501 diverse temperate genotypes grown in replicate in five environments. Analysis of variance revealed environment explained the highest percent of the variation (51.5%), followed by genotype (15.6%) and genotype-by-environment interaction (11.2%). A genome-wide association study identified 26 significant loci across five environments that explained between 5.04% and 16.01% (average = 10.41%). However, genome-wide markers explained 10.54% to 45.99% (average = 31.68%) of the variation, indicating the genetic architecture of this trait is likely complex and controlled by many loci of small effect. This study provides a high-throughput method to evaluate moisture content during nixtamalization that is feasible at the scale of a breeding program and provides important information about the factors contributing to variation of this trait for breeders and food companies to make future strategies to improve this important processing trait. Key MessageMoisture content during nixtamalization can be accurately predicted from NIR spectroscopy when coupled with a support vector machine (SVM) model, is strongly modulated by the environment, and has a complex genetic architecture.

plant biology↗

Genetic Architecture of Kernel Compositional Variation in a Maize Diversity Panel

Maize (Zea mays L.) is a multi-purpose row crop grown worldwide, which overtime has often been bred for increased yield at the detriment of lower composition grain quality. Some knowledge of the genetic factors that affect quality traits has been discovered through the study of classical maize mutants. However, much of the underlying genetic architecture controlling these traits and the interaction between these traits remains unknown. To better understand variation that exists for grain compositional traits in maize, we evaluated 501 diverse temperate maize inbred lines in five unique environments and predicted 16 compositional traits (e.g. carbohydrates, protein, starch) based on the output of near-infrared (NIR) spectroscopy. Phenotypic analysis found substantial variation for compositional traits and the majority of variation was explained by genetic and environmental factors. Correlations and trade-offs among traits in different maize types (e.g. dent, sweetcorn, popcorn) were explored and significant differences and correlations were detected. In total, 22.9-71.1% of the phenotypic variation across these traits could be explained using 2,386,666 single nucleotide polymorphism (SNP) markers generated from whole genome resequencing data. A genome-wide association study (GWAS) was conducted using these same markers and found 70 statistically significant loci for 12 compositional traits. This study provides valuable insights in the phenotypic variation and genetic architecture underlying compositional traits that can be used in breeding programs for improving maize grain quality. Core IdeasO_LIUnderstanding kernel compositional variation is important for food grade corn improvement. C_LIO_LIGenetic and environmental factors account for most of the variation in compositional traits. C_LIO_LIA broad range in trait heritabilities was observed across compositional traits. C_LIO_LICompositional trade-offs will be important to consider when conducting multitrait breeding. C_LIO_LICompositional traits are mostly controlled by a large number of small effect loci. C_LI

plant biology↗

Divergent epigenetic profiles from two differentially impacted wild populationsof estuarine cordgrass (Sporobolus alterniflorus)

The effects of urbanization on watershed ecosystems present critical challenges to modern survival. Organisms in urbanized areas experience high rates of evolutionary change, but genetic adaptation alone cannot mitigate the rapid and severe effects of urbanization on biodiversity. Highly resilient, foundation species are key to maintaining an ecosystems integrity in the face of urban stressors. However, the rapid collapse and disappearance of watershed ecosystems calls into question the extent to which we can rely on such species for their services. Our research investigates the molecular mechanisms by which the foundation ecosystems provider, Sporobolus alterniflorus, adapts to life in an urbanized environment. To elucidate these mechanisms, we quantified changes in global DNA methylation (% 5-mC) as a result of acute heat stress. Specimens from two differentially impacted populations across an urban to suburban geographical transect formed the basis of this study. These two populations of Sporobolus alterniflora exhibit inverse global DNA methylation patterns when exposed to the same acute heat stress. Our findings suggest that epigenetic mechanisms, such as DNA methylation, control rapid and transient adaptation, in the form of differential stress responses, to distinct environment challenges. Highlights for manuscript submissionO_LI{blacksquare} estuarine grasses native to the Bronx River, NY face stresses associated with low dissolved oxygen and urbanization C_LIO_LI{blacksquare} differentially impacted populations of estuarine grasses exhibit inverse global DNA methylation profiles in response to acute heat stress C_LIO_LI{blacksquare} DNA methylation may represent a mechanism by which plants transiently respond to environmental stressors, and this may represent a form of rapid adaptive evolution C_LIO_LI{blacksquare} stress priming by transgenerational epigenetic modification may enhance fitness in grasses native to the heavily impacted Bronx River estuary C_LI

plant biology↗