Range-wide evolutionary relationships and historical demography of brown bears (Ursus arctos) revealed by whole-genome sequencing of isolated central Asian populations.

Phylogeographic studies uncover hidden pathways of divergence and inform conservation. Brown bears (Ursus arctos) have one of the broadest distributions of all land mammals, ranging from Eurasia to North America, and are an important model for evolutionary studies. Although several whole genomes were available for individuals from North America, Europe and Asia, limited whole-genome data were available from Central Asia, including the highly imperilled brown bears in the Gobi Desert. To fill this knowledge gap, we sequenced whole genomes from nine Asian brown bears from the Gobi Desert of Mongolia, Northern Mongolia and the Himalayas of Pakistan. We combined these data with published brown bear sequences from Europe, Asia and North America, as well as other bear species. Our goals were to determine the evolutionary relationships among brown bear populations worldwide, their genetic diversity and their historical demography. Our analyses revealed five major lineages of brown bears based on a filtered set of 684,081 single nucleotide polymorphisms. We found distinct evolutionary lineages of brown bears in the Gobi, Himalayas, northern Mongolia, Europe and North America. The lowest level of genetic diversity and the highest level of inbreeding were found in Pakistan, the Gobi Desert and Central Italy. Furthermore, the effective population size (Ne ) for all brown bears decreased over the last 70,000 years. Our results confirm the genetic distinctiveness and ancient lineage of brown bear subspecies in the Gobi Desert of Mongolia and the Himalayas of Pakistan and highlight their importance for conservation.

Corridor-based approach with spatial cross-validation reveals scale-dependent effects of geographic distance, human footprint and canopy cover on grizzly bear genetic connectivity.

Understanding how human infrastructure and other landscape attributes affect genetic differentiation in animals is an important step for identifying and maintaining dispersal corridors for these species. We built upon recent advances in the field of landscape genetics by using an individual-based and multiscale approach to predict landscape-level genetic connectivity for grizzly bears (Ursus arctos) across ~100,000 km2 in Canada's southern Rocky Mountains. We used a genetic dataset with 1156 unique individuals genotyped at nine microsatellite loci to identify landscape characteristics that influence grizzly bear gene flow at multiple spatial scales and map predicted genetic connectivity through a matrix of rugged terrain, large protected areas, highways and a growing human footprint. Our corridor-based modelling approach used a machine learning algorithm that objectively parameterized landscape resistance, incorporated spatial cross validation and variable selection and explicitly accounted for isolation by distance. This approach avoided overfitting, discarded variables that did not improve model performance across withheld test datasets and spatial predictive capacity compared to random cross-validation. We found that across all spatial scales, geographic distance explained more variation in genetic differentiation in grizzly bears than landscape variables. Human footprint inhibited connectivity across all spatial scales, while open canopies inhibited connectivity at the broadest spatial scale. Our results highlight the negative effect of human footprint on genetic connectivity, provide strong evidence for using spatial cross-validation in landscape genetics analyses and show that multiscale analyses provide additional information on how landscape variables affect genetic differentiation.

Screening the complex biological behavior of late lanthanides through genome-wide interactions.

Despite their similar physicochemical properties, recent studies have demonstrated that lanthanides can display different biological behaviors. Hence, the lanthanide series can be divided into three parts, namely early, mid, and late lanthanides, based on their interactions with biological systems. In particular, the late lanthanides demonstrate distinct, but poorly understood biological activity. In the current study, we employed genome-wide functional screening to help understand biological effects of exposure to Yb(III) and Lu(III), which were selected as representatives of the late lanthanides. As a model organism, we used Saccharomyces cerevisiae, since it shares many biological functions with humans. Analysis of the functional screening results indicated toxicity of late lanthanides is consistent with disruption of vesicle-mediated transport, and further supported a role for calcium transport processes and mitophagy in mitigating toxicity. Unexpectedly, our analysis suggested that late lanthanides target proteins with SH3 domains, which may underlie the observed toxicity. This study provides fundamental insights into the unique biological chemistry of late lanthanides, which may help devise new avenues toward the development of decorporation strategies and bio-inspired separation processes.

Modeling Behavior and Vaccine Hesitancy Using Twitter-Derived US Population Sentiment during the COVID-19 Pandemic to Predict Daily Vaccination Inoculations.

The sentiment analysis of social media for predicting behavior during a pandemic is seminal in nature. As an applied contribution, we present sentiment-based regression models for predicting the United States COVID-19 first dose, second dose, and booster daily inoculations from 1 June 2021 to 31 March 2022. The models merge independent variables representing fear of the virus and vaccine hesitancy. Large correlations exceeding 77% and 84% for the first-dose and booster-dose models inspire confidence in the merger of the independent variables. Death count as a traditional measure of fear is a lagging indicator of inoculations, while Twitter-positive and -negative tweets are strong predictors of inoculations. Thus, the use of sentiment analysis for predicting inoculations is strongly supported with administrative events being catalysts for tweets. Non-inclusion in the second-dose regression model of data occurring before the 1 June 2021 timeframe appear to limit the second-dose model results-only achieving a moderate correlation exceeding 53%. Limiting tweet collection to geolocated tweets does not encompass the entire US Twitter population. Nonetheless, results from Kaiser Family Foundation (KFF) surveys appear to generally support the regression factors common to the first-dose and booster-dose regression models and their results.

Reconsidering lateral vocalisation: Evidence from perception and production of Australian English /l/.

Lateral vocalisation is assumed to arise from changes in coronal articulation but is typically characterised perceptually without linking the vocalised percept to a coronal articulation. Therefore, we examined how listeners' perception of coda /l/ as vocalised relates to coronal closure. Perceptual stimuli were acquired by recording laterals produced by six speakers of Australian English using electromagnetic articulography (EMA). Tongue tip closure was monitored for each lateral in the EMA data. Increased incidence of incomplete coronal closure was found in coda /l/ relative to onset /l/. Having verified that the dataset included /l/ tokens produced with incomplete coronal closure-a primary articulatory cue of vocalised /l/-we conducted a perception study in which four highly experienced auditors rated each coda /l/ token from vocalised (3) to non-vocalised (0). An ordinal mixed model showed that increased tongue tip (TT) aperture and delay correlated with vocalised percept, but auditors ratings were characterised by a lack of inter-rater reliability. While the correlation between increased TT aperture, delay, and vocalised percept shows that there is some reliability in auditory classification, variation between auditors suggests that listeners may be sensitive to different sets of cues associated with lateral vocalisation that are not yet entirely understood.

Identifying Toxicity Mechanisms Associated with Early Lanthanide Exposure through Multidimensional Genome-Wide Screening.

Lanthanides are a series of elements essential to a wide range of applications, from clean energy production to healthcare. Despite their presence in multiple products and technologies, their toxicological characteristics have been only partly studied. Recently, our group has employed a genomic approach to extensively characterize the toxicity mechanisms of lanthanides. Even though we identified substantially different behaviors for mid and late lanthanides, the toxicological profiles of early lanthanides remained elusive. Here, we overcome this gap by describing a multidimensional genome-wide toxicogenomic study for two early lanthanides, namely, lanthanum and praseodymium. We used Saccharomyces cerevisiae as a model system since its genome shares many biological pathways with humans. By performing functional analysis and protein-protein interaction network analysis, we identified the main genes and proteins that participate in the yeast response to counter metal harmful effects. Moreover, our analysis also highlighted key enzymes that are dysregulated by early lanthanides, inducing cytotoxicity. Several of these genes and proteins have human orthologues, indicating that they may also participate in the human response against the metals. By highlighting the key genes and proteins in lanthanide-induced toxicity, this work may contribute to the development of new prophylactic and therapeutic strategies against lanthanide harmful exposures.

Evolution of Select Epidemiological Modeling and the Rise of Population Sentiment Analysis: A Literature Review and COVID-19 Sentiment Illustration.

With social networking enabling the expressions of billions of people to be posted online, sentiment analysis and massive computational power enables systematic mining of information about populations including their affective states with respect to epidemiological concerns during a pandemic. Gleaning rationale for behavioral choices, such as vaccine hesitancy, from public commentary expressed through social media channels may provide quantifiable and articulated sources of feedback that are useful for rapidly modifying or refining pandemic spread predictions, health protocols, vaccination offerings, and policy approaches. Additional potential gains of sentiment analysis may include lessening of vaccine hesitancy, reduction in civil disobedience, and most importantly, better healthcare outcomes for individuals and their communities. In this article, we highlight the evolution of select epidemiological models; conduct a critical review of models in terms of the level and depth of modeling of social media, social network factors, and sentiment analysis; and finally, partially illustrate sentiment analysis using COVID-19 Twitter data.

Delineating toxicity mechanisms associated with MRI contrast enhancement through a multidimensional toxicogenomic profiling of gadolinium.

Gadolinium is a metal used in contrast agents for magnetic resonance imaging. Although gadolinium is widely used in clinical settings, many concerns regarding its toxicity and bioaccumulation after gadolinium-based contrast agent administration have been raised and published over the last decade. To date, most toxicological studies have focused on identifying acute effects following gadolinium exposure, rather than investigating associated toxicity mechanisms. In this study, we employ functional toxicogenomics to assess mechanistic interactions of gadolinium with Saccharomyces cerevisiae. Furthermore, we determine which mechanisms are conserved in humans, and their implications for diseases related to the use of gadolinium-based contrast agents in medicine. A homozygous deletion pool of 4291 strains were screened to identify biological functions and pathways disturbed by the metal. Gene ontology and pathway enrichment analyses showed endocytosis and vesicle-mediated transport as the main yeast response to gadolinium, while certain metabolic processes, such as glycosylation, were the primary disrupted functions after the metal treatments. Cluster and protein-protein interaction network analyses identified proteins mediating vesicle-mediated transport through the Golgi apparatus and the vacuole, and vesicle cargo exocytosis as key components to reduce the metal toxicity. Moreover, the metal seemed to induce cytotoxicity by disrupting the function of enzymes (e.g. transferases and proteases) and chaperones involved in metabolic processes. Several of the genes and proteins associated with gadolinium toxicity are conserved in humans, suggesting that they may participate in pathologies linked to gadolinium-based contrast agent exposures. We thereby discuss the potential role of these conserved genes and gene products in gadolinium-induced nephrogenic systemic fibrosis, and propose potential prophylactic strategies to prevent its adverse health effects.

Multidimensional genome-wide screening in yeast provides mechanistic insights into europium toxicity.

Europium is a lanthanide metal that is highly valued in optoelectronics. Even though europium is used in many commercial products, its toxicological profile has only been partially characterized, with most studies focusing on identifying lethal doses in different systems or bioaccumulation in vivo. This paper describes a genome-wide toxicogenomic study of europium in Saccharomyces cerevisiae, which shares many biological functions with humans. By using a multidimensional approach and functional and network analyses, we have identified a group of genes and proteins associated with the yeast responses to ameliorate metal toxicity, which include metal discharge paths through vesicle-mediated transport, paths to regulate biologically relevant cations, and processes to reduce metal-induced stress. Furthermore, the analyses indicated that europium promotes yeast toxicity by disrupting the function of chaperones and cochaperones, which have metal-binding sites. Several of the genes and proteins highlighted in our study have human orthologues, suggesting they may participate in europium-induced toxicity in humans. By identifying the endogenous targets of europium as well as the already existing paths that can decrease its toxicity, we can determine specific genes and proteins that may help to develop future therapeutic strategies.

Genome-wide toxicogenomic study of the lanthanides sheds light on the selective toxicity mechanisms associated with critical materials.

Lanthanides are a series of critical elements widely used in multiple industries, such as optoelectronics and healthcare. Although initially considered to be of low toxicity, concerns have emerged during the last few decades over their impact on human health. The toxicological profile of these metals, however, has been incompletely characterized, with most studies to date solely focusing on one or two elements within the group. In the current study, we assessed potential toxicity mechanisms in the lanthanide series using a functional toxicogenomics approach in baker's yeast, which shares many cellular pathways and functions with humans. We screened the homozygous deletion pool of 4,291 Saccharomyces cerevisiae strains with the lanthanides and identified both common and unique functional effects of these metals. Three very different trends were observed within the lanthanide series, where deletions of certain proteins on membranes and organelles had no effect on the cellular response to early lanthanides while inducing yeast sensitivity and resistance to middle and late lanthanides, respectively. Vesicle-mediated transport (primarily endocytosis) was highlighted by both gene ontology and pathway enrichment analyses as one of the main functions disturbed by the majority of the metals. Protein-protein network analysis indicated that yeast response to lanthanides relied on proteins that participate in regulatory paths used for calcium (and other biologically relevant cations), and lanthanide toxicity included disruption of biosynthetic pathways by enzyme inhibition. Last, multiple genes and proteins identified in the network analysis have human orthologs, suggesting that those may also be targeted by lanthanides in humans.

Spectral contrast reduction in Australian English /l/-final rimes.

Vowel contrasts may be reduced or neutralized before coda laterals in English [Bernard (1985). The Cultivated Australian: Festschrift in Honour of Arthur Delbridge, pp. 319-332; Labov, Ash, and Boberg (2008). The Atlas of North American English, Phonetics and Sound Change (Gruyter Mouton, Berlin); Palethorpe and Cox (2003). International Seminar on Speech Production (Macquaire University, Sydney, Australia)], but the acoustic characteristics of vowel-lateral interaction in Australian English (AusE) rimes have not been systematically examined. Spectral and temporal properties of 16 pre-lateral and 16 pre-obstruent vowels produced by 29 speakers of AusE were compared. Acoustic vowel similarity in both environments was captured using random forest classification and hierarchical cluster analysis of the first three DCT coefficients of F1, F2, and F3, and duration values. Vowels preceding /l/ codas showed overall increased confusability compared to vowels preceding /d/ codas. In particular, reduced spectral contrast was found for the rime pairs /iːl-ɪl/ (feel-fill), /ʉːl-ʊl/ (fool-full), /əʉl-ɔl/ (dole-doll), and /æɔl-æl/ (howl-Hal). Potential articulatory explanations and implications for sound change are discussed.

Characterizing spoken responses in masked-onset priming of reading aloud using articulography.

A key method for studying articulatory planning at different levels of phonological organization is masked-onset priming. In previous work using that paradigm the dependent variable has been acoustic response time (RT). We used electromagnetic articulography to measure articulatory RTs and the articulatory properties of speech gestures in non-word production in a masked-onset priming experiment. Initiation of articulation preceded acoustic response onset by 199 ms, but the acoustic lag varied by up to 63 ms, depending on the phonological structure of the target. Onset priming affected articulatory response latency, but had no effect on gestural duration, inter-gestural coordination, or articulatory velocity. This is consistent with an account of the masked-onset priming effect in which the computation from orthography of an abstract phonological representation of the target is initiated earlier in the primed than in the unprimed condition. We discuss the implications of these findings for models of speech production and the scope of articulatory planning and execution.

The ecology of human-carnivore coexistence.

With a shrinking supply of wilderness and growing recognition that top predators can have a profound influence on ecosystems, the persistence of large carnivores in human-dominated landscapes has emerged as one of the greatest conservation challenges of our time. Carnivores fascinate society, yet these animals pose threats to people living near them, resulting in high rates of carnivore death near human settlements. We used 41 y of demographic data for more than 2,500 brown bears-one of the world's most widely distributed and conflict-prone carnivores-to understand the behavioral and demographic mechanisms promoting carnivore coexistence in human-dominated landscapes. Bear mortality was high and unsustainable near people, but a human-induced shift to nocturnality facilitated lower risks of bear mortality and rates of conflict with people. Despite these behavioral shifts, projected population growth rates for bears in human-dominated areas revealed a source-sink dynamic. Despite some female bears successfully reproducing in the sink areas, bear persistence was reliant on a supply of immigrants from areas with minimal human influence (i.e., wilderness). Such mechanisms of coexistence reveal a striking paradox: Connectivity to wilderness areas supplies bears that likely will die from people, but these bears are essential to avert local extirpation. These insights suggest carnivores contribute to human-carnivore coexistence through behavioral and demographic mechanisms, and that connected wilderness is critical to sustain coexistence landscapes.

Phylogeography, genetic diversity, and connectivity of brown bear populations in Central Asia.

Knowledge of genetic diversity and population structure is critical for conservation and management planning at the population level within a species' range. Many brown bear populations in Central Asia are small and geographically isolated, yet their phylogeographic relationships, genetic diversity, and contemporary connectivity are poorly understood. To address this knowledge gap, we collected brown bear samples from the Gobi Desert (n = 2360), Altai, Sayan, Khentii, and Ikh Khyangan mountains of Mongolia (n = 79), and Deosai National Park in the Himalayan Mountain Range of Pakistan (n = 5) and generated 927 base pairs of mitochondrial DNA (mtDNA) sequence data and genotypes at 13 nuclear DNA microsatellite loci. We documented high levels of mtDNA and nDNA diversity in the brown bear populations of northern Mongolia (Altai, Sayan, Buteeliin nuruu and Khentii), but substantially lower diversity in brown bear populations in the Gobi Desert and Himalayas of Pakistan. We detected 3 brown bear mtDNA phylogeographic groups among bears of the region, with clade 3a1 in Sayan, Khentii, and Buteeliin nuruu mountains, clade 3b in Altai, Sayan, Buteeliin nuruu, Khentii, and Ikh Khyangan, and clade 6 in Gobi and Pakistan. Our results also clarified the phylogenetic relationships and divergence times with other brown bear mtDNA clades around the world. The nDNA genetic structure analyses revealed distinctiveness of Gobi bears and different population subdivisions compared to mtDNA results. For example, genetic distance for nDNA microsatellite loci between the bears in Gobi and Altai (FST = 0.147) was less than that of the Gobi and Pakistan (FST = 0.308) suggesting more recent male-mediated nuclear gene flow between Gobi and Altai than between Gobi and the Pakistan bears. Our results provide valuable information for conservation and management of bears in this understudied region of Central Asia and highlight the need for special protection and additional research on Gobi brown bears.

Genetic tagging in the Anthropocene: scaling ecology from alleles to ecosystems.

The Anthropocene is an era of marked human impact on the world. Quantifying these impacts has become central to understanding the dynamics of coupled human-natural systems, resource-dependent livelihoods, and biodiversity conservation. Ecologists are facing growing pressure to quantify the size, distribution, and trajectory of wild populations in a cost-effective and socially acceptable manner. Genetic tagging, combined with modern computational and genetic analyses, is an under-utilized tool to meet this demand, especially for wide-ranging, elusive, sensitive, and low-density species. Genetic tagging studies are now revealing unprecedented insight into the mechanisms that control the density, trajectory, connectivity, and patterns of human-wildlife interaction for populations over vast spatial extents. Here, we outline the application of, and ecological inferences from, new analytical techniques applied to genetically tagged individuals, contrast this approach with conventional methods, and describe how genetic tagging can be better applied to address outstanding questions in ecology. We provide example analyses using a long-term genetic tagging dataset of grizzly bears in the Canadian Rockies. The genetic tagging toolbox is a powerful and overlooked ensemble that ecologists and conservation biologists can leverage to generate evidence and meet the challenges of the Anthropocene.

The effect of autostereoscopic holograms on anatomical knowledge: a randomised trial.

CONTEXT: Three-dimensional (3-D) visualisation in anatomical education has been shown to be broadly beneficial for students. However, there is limited research on the relative efficacy of 3-D modalities. This study compares knowledge performance, mental effort and instructional efficiency between autostereoscopic 3-D visualisation (holograms), monoscopic 3-D visualisation (3-DPDFs) and a control (2-D printed images). METHODS: A cardiac anatomy model was used to generate holograms, 3-DPDFs and 2-D printed images. Nursing student participants (n = 179) were randomised into three groups: holograms (n = 60), 3-DPDFs (n = 60) and printed images (n = 59). Participants completed a pre-test followed by a self-study period using the anatomical visualisation. Afterwards, participants completed the NASA-Task Load Index (NASA-TLX) cognitive load instrument and a knowledge post-test. RESULTS: Post-test results showed participants studying with holograms (median = 80.0, interquartile range [IQR] = 66.7-86.7) performed significantly better regarding cardiac anatomy knowledge than participants using 3-DPDF (median = 66.7, IQR = 53.3-80.0, p = 0.008) or printed images (median = 66.7, IQR = 53.3-80.0, p = 0.007). Mental effort scores, on a scale from 1 to 20, showed hologram (mean = 4.9, standard deviation [SD] = 3.56) and 3-DPDF participants (mean = 4.9, SD = 3.79) reported significantly lower cognitive load than printed images (mean = 7.5, SD = 4.9, p < 0.005). Instructional efficiency (E) of holograms (E = 0.35) was significantly higher than printed images (E = -0.36, p < 0.001), although not significantly higher than 3-DPDF (E = 0.03, p = 0.097). CONCLUSIONS: Participants using holograms demonstrated significant knowledge improvement over printed images and monoscopic 3-DPDF models, suggesting additional depth cues from holographic visualisation provide benefit in understanding spatial anatomy. Mental effort scores and instructional efficiency of holograms indicate holograms are a cognitively efficient instructional medium. These findings highlight the need for further study of novel 3-D technologies and learning performance.

Acoustic characteristics of Punjabi retroflex and dental stops.

The phonological category "retroflex" is found in many Indo-Aryan languages; however, it has not been clearly established which acoustic characteristics reliably differentiate retroflexes from other coronals. This study investigates the acoustic phonetic properties of Punjabi retroflex /ʈ/ and dental /ʈ̪/ in word-medial and word-initial contexts across /i e a o u/, and in word-final context across /i a u/. Formant transitions, closure and release durations, and spectral moments of release bursts are compared in 2280 stop tokens produced by 30 speakers. Although burst spectral measures and formant transitions do not consistently differentiate retroflexes from dentals in some vowel contexts, stop release duration, and total stop duration reliably differentiate Punjabi retroflex and dental stops across all word contexts and vocalic environments. These results suggest that Punjabi coronal place contrasts are signaled by the complex interaction of temporal and spectral cues.

Quantitative analysis of protein interaction network dynamics in yeast.

Many cellular functions are mediated by protein-protein interaction networks, which are environment dependent. However, systematic measurement of interactions in diverse environments is required to better understand the relative importance of different mechanisms underlying network dynamics. To investigate environment-dependent protein complex dynamics, we used a DNA-barcode-based multiplexed protein interaction assay in Saccharomyces cerevisiae to measure in vivo abundance of 1,379 binary protein complexes under 14 environments. Many binary complexes (55%) were environment dependent, especially those involving transmembrane transporters. We observed many concerted changes around highly connected proteins, and overall network dynamics suggested that "concerted" protein-centered changes are prevalent. Under a diauxic shift in carbon source from glucose to ethanol, a mass-action-based model using relative mRNA levels explained an estimated 47% of the observed variance in binary complex abundance and predicted the direction of concerted binary complex changes with 88% accuracy. Thus, we provide a resource of yeast protein interaction measurements across diverse environments and illustrate the value of this resource in revealing mechanisms of network dynamics.

Characterizing Articulation in Apraxic Speech Using Real-Time Magnetic Resonance Imaging.

Purpose: Real-time magnetic resonance imaging (MRI) and accompanying analytical methods are shown to capture and quantify salient aspects of apraxic speech, substantiating and expanding upon evidence provided by clinical observation and acoustic and kinematic data. Analysis of apraxic speech errors within a dynamic systems framework is provided and the nature of pathomechanisms of apraxic speech discussed. Method: One adult male speaker with apraxia of speech was imaged using real-time MRI while producing spontaneous speech, repeated naming tasks, and self-paced repetition of word pairs designed to elicit speech errors. Articulatory data were analyzed, and speech errors were detected using time series reflecting articulatory activity in regions of interest. Results: Real-time MRI captured two types of apraxic gestural intrusion errors in a word pair repetition task. Gestural intrusion errors in nonrepetitive speech, multiple silent initiation gestures at the onset of speech, and covert (unphonated) articulation of entire monosyllabic words were also captured. Conclusion: Real-time MRI and accompanying analytical methods capture and quantify many features of apraxic speech that have been previously observed using other modalities while offering high spatial resolution. This patient's apraxia of speech affected the ability to select only the appropriate vocal tract gestures for a target utterance, suppressing others, and to coordinate them in time.