ASU Scholarship Showcase

Linnorm is a novel normalization and transformation method for the analysis of single cell RNA sequencing (scRNA-seq) data. Linnorm is developed to remove technical noises and simultaneously preserve biological variations in scRNA-seq data, such that existing statistical methods can be improved. Using real scRNA-seq data, we compared Linnorm with existing normalization methods, including NODES, SAMstrt, SCnorm, scran, DESeq and TMM. Linnorm shows advantages in speed, technical noise removal and preservation of cell heterogeneity, which can improve existing methods in the discovery of novel subtypes, pseudo-temporal ordering of cells, clustering analysis, etc. Linnorm also performs better than existing DEG analysis methods, including BASiCS, NODES, SAMstrt, Seurat and DESeq2, in false positive rate control and accuracy.

Stone-tipped weapons were a significant innovation for Middle Pleistocene hominins. Hafted hunting technology represents the development of new cognitive and social learning mechanisms within the genus Homo, and may have provided a foraging advantage over simpler forms of hunting technology, such as a sharpened wooden spear. However, the nature of this foraging advantage has not been confirmed. Experimental studies and ethnographic reports provide conflicting results regarding the relative importance of the functional, economic, and social roles of hafted hunting technology. The controlled experiment reported here was designed to test the functional hypothesis for stone-tipped weapons using spears and ballistics gelatin. It differs from previous investigations of this type because it includes a quantitative analysis of wound track profiles and focuses specifically on hand-delivered spear technology. Our results do not support the hypothesis that tipped spears penetrate deeper than untipped spears. However, tipped spears create a significantly larger inner wound cavity that widens distally. This inner wound cavity is analogous to the permanent wound cavity in ballistics research, which is considered the key variable affecting the relative ‘stopping power’ or ‘killing power’ of a penetrating weapon. Tipped spears conferred a functional advantage to Middle Pleistocene hominins, potentially affecting the frequency and regularity of hunting success with important implications for human adaptation and life history.

Introduction: Urbanization can considerably impact animal ecology, evolution, and behavior. Among the new conditions that animals experience in cities is anthropogenic noise, which can limit the sound space available for animals to communicate using acoustic signals. Some urban bird species increase their song frequencies so that they can be heard above low-frequency background city noise. However, the ability to make such song modifications may be constrained by several morphological factors, including bill gape, size, and shape, thereby limiting the degree to which certain species can vocally adapt to urban settings. We examined the relationship between song characteristics and bill morphology in a species (the house finch, Haemorhous mexicanus) where both vocal performance and bill size are known to differ between city and rural animals.

Results: We found that bills were longer and narrower in more disturbed, urban areas. We observed an increase in minimum song frequency of urban birds, and we also found that the upper frequency limit of songs decreased in direct relation to bill morphology.

Conclusions: These findings are consistent with the hypothesis that birds with longer beaks and therefore longer vocal tracts sing songs with lower maximum frequencies because longer tubes have lower-frequency resonances. Thus, for the first time, we reveal dual constraints (one biotic, one abiotic) on the song frequency range of urban animals. Urban foraging pressures may additionally interact with the acoustic environment to shape bill traits and vocal performance.

The Middle Stone Age (MSA) is associated with early evidence for symbolic material culture and complex technological innovations. However, one of the most visible aspects of MSA technologies are unretouched triangular stone points that appear in the archaeological record as early as 500,000 years ago in Africa and persist throughout the MSA. How these tools were being used and discarded across a changing Pleistocene landscape can provide insight into how MSA populations prioritized technological and foraging decisions. Creating inferential links between experimental and archaeological tool use helps to establish prehistoric tool function, but is complicated by the overlaying of post-depositional damage onto behaviorally worn tools. Taphonomic damage patterning can provide insight into site formation history, but may preclude behavioral interpretations of tool function. Here, multiple experimental processes that form edge damage on unretouched lithic points from taphonomic and behavioral processes are presented. These provide experimental distributions of wear on tool edges from known processes that are then quantitatively compared to the archaeological patterning of stone point edge damage from three MSA lithic assemblages—Kathu Pan 1, Pinnacle Point Cave 13B, and Die Kelders Cave 1. By using a model-fitting approach, the results presented here provide evidence for variable MSA behavioral strategies of stone point utilization on the landscape consistent with armature tips at KP1, and cutting tools at PP13B and DK1, as well as damage contributions from post-depositional sources across assemblages. This study provides a method with which landscape-scale questions of early modern human tool-use and site-use can be addressed.

We formulate an in silico model of pathogen avoidance mechanism and investigate its impact on defensive behavioural measures (e.g., spontaneous social exclusions and distancing, crowd avoidance and voluntary vaccination adaptation). In particular, we use SIR(B)S (e.g., susceptible-infected-recovered with additional behavioural component) model to investigate the impact of homo-psychologicus aspects of epidemics. We focus on reactionary behavioural changes, which apply to both social distancing and voluntary vaccination participations. Our analyses reveal complex relationships between spontaneous and uncoordinated behavioural changes, the emergence of its contagion properties, and mitigation of infectious diseases. We find that the presence of effective behavioural changes can impede the persistence of disease. Furthermore, it was found that under perfect effective behavioural change, there are three regions in the response factor (e.g., imitation and/or reactionary) and behavioural scale factor (e.g., global/local) factors ρ–α behavioural space. Mainly, (1) disease is always endemic even in the presence of behavioural change, (2) behavioural-prevalence plasticity is observed and disease can sometimes be eradication, and (3) elimination of endemic disease under permanence of permanent behavioural change is achieved. These results suggest that preventive behavioural changes (e.g., non-pharmaceutical prophylactic measures, social distancing and exclusion, crowd avoidance) are influenced by individual differences in perception of risks and are a salient feature of epidemics. Additionally, these findings indicates that care needs to be taken when considering the effect of adaptive behavioural change in predicting the course of epidemics, and as well as the interpretation and development of the public health measures that account for spontaneous behavioural changes.

Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6C^low and Ly6C^hi) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E₂ is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the Ep3 receptor in mice suppresses accumulation of Ly6C^low Mos/Mps in infarcted hearts. Ep3 deletion in Mos/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones. Ep3 deficiency diminishes CX3C chemokine receptor 1 (CX3CR1) expression and vascular endothelial growth factor (VEGF) secretion in Mos/Mps by suppressing TGFβ1 signaling and subsequently inhibits Ly6C^low Mos/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE₂/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6C^low Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.

Modeling of transcriptional regulatory networks (TRNs) has been increasingly used to dissect the nature of gene regulation. Inference of regulatory relationships among transcription factors (TFs) and genes, especially among multiple TFs, is still challenging. In this study, we introduced an integrative method, LogicTRN, to decode TF–TF interactions that form TF logics in regulating target genes. By combining cis-regulatory logics and transcriptional kinetics into one single model framework, LogicTRN can naturally integrate dynamic gene expression data and TF-DNA-binding signals in order to identify the TF logics and to reconstruct the underlying TRNs. We evaluated the newly developed methodology using simulation, comparison and application studies, and the results not only show their consistence with existing knowledge, but also demonstrate its ability to accurately reconstruct TRNs in biological complex systems.

Neuropharmacological effects of psychedelics have profound cognitive, emotional, and social effects that inspired the development of cultures and religions worldwide. Findings that psychedelics objectively and reliably produce mystical experiences press the question of the neuropharmacological mechanisms by which these highly significant experiences are produced by exogenous neurotransmitter analogs. Humans have a long evolutionary relationship with psychedelics, a consequence of psychedelics' selective effects for human cognitive abilities, exemplified in the information rich visionary experiences. Objective evidence that psychedelics produce classic mystical experiences, coupled with the finding that hallucinatory experiences can be induced by many non-drug mechanisms, illustrates the need for a common model of visionary effects. Several models implicate disturbances of normal regulatory processes in the brain as the underlying mechanisms responsible for the similarities of visionary experiences produced by psychedelic and other methods for altering consciousness. Similarities in psychedelic-induced visionary experiences and those produced by practices such as meditation and hypnosis and pathological conditions such as epilepsy indicate the need for a general model explaining visionary experiences. Common mechanisms underlying diverse alterations of consciousness involve the disruption of normal functions of the prefrontal cortex and default mode network (DMN). This interruption of ordinary control mechanisms allows for the release of thalamic and other lower brain discharges that stimulate a visual information representation system and release the effects of innate cognitive functions and operators. Converging forms of evidence support the hypothesis that the source of psychedelic experiences involves the emergence of these innate cognitive processes of lower brain systems, with visionary experiences resulting from the activation of innate processes based in the mirror neuron system (MNS).

The coastal environments of South Africa’s Cape Floristic Region (CFR) provide some of the earliest and most abundant evidence for the emergence of cognitively modern humans. In particular, the south coast of the CFR provided a uniquely diverse resource base for hunter-gatherers, which included marine shellfish, game, and carbohydrate-bearing plants, especially those with Underground Storage Organs (USOs). It has been hypothesized that these resources underpinned the continuity of human occupation in the region since the Middle Pleistocene. Very little research has been conducted on the foraging potential of carbohydrate resources in the CFR. This study focuses on the seasonal availability of plants with edible carbohydrates at six-weekly intervals over a two-year period in four vegetation types on South Africa’s Cape south coast. Different plant species were considered available to foragers if the edible carbohydrate was directly (i.e. above-ground edible portions) or indirectly (above-ground indications to below-ground edible portions) visible to an expert botanist familiar with this landscape. A total of 52 edible plant species were recorded across all vegetation types. Of these, 33 species were geophytes with edible USOs and 21 species had aboveground edible carbohydrates. Limestone Fynbos had the richest flora, followed by Strandveld, Renosterveld and lastly, Sand Fynbos. The availability of plant species differed across vegetation types and between survey years. The number of available USO species was highest for a six-month period from winter to early summer (Jul–Dec) across all vegetation types. Months of lowest species’ availability were in mid-summer to early autumn (Jan–Apr); the early winter (May–Jun) values were variable, being highest in Limestone Fynbos. However, even during the late summer carbohydrate “crunch,” 25 carbohydrate bearing species were visible across the four vegetation types. To establish a robust resource landscape will require additional spatial mapping of plant species abundances. Nonetheless, our results demonstrate that plant-based carbohydrate resources available to Stone Age foragers of the Cape south coast, especially USOs belonging to the Iridaceae family, are likely to have comprised a reliable and nutritious source of calories over most of the year.

Color vision in birds is mediated by four types of cone photoreceptors whose maximal sensitivities (λ_max) are evenly spaced across the light spectrum. In the course of avian evolution, the λ_max of the most shortwave-sensitive cone, SWS1, has switched between violet (λ_max > 400 nm) and ultraviolet (λ_max < 380 nm) multiple times. This shift of the SWS1 opsin is accompanied by a corresponding short-wavelength shift in the spectrally adjacent SWS2 cone. Here, we show that SWS2 cone spectral tuning is mediated by modulating the ratio of two apocarotenoids, galloxanthin and 11’,12’-dihydrogalloxanthin, which act as intracellular spectral filters in this cell type. We propose an enzymatic pathway that mediates the differential production of these apocarotenoids in the avian retina, and we use color vision modeling to demonstrate how correlated evolution of spectral tuning is necessary to achieve even sampling of the light spectrum and thereby maintain near-optimal color discrimination.