BWSNet: Automatic Perceptual Assessment of Audio Signals

This paper introduces BWSNet, a model that can be trained from raw human judgements obtained through a Best-Worst scaling (BWS) experiment. It maps sound samples into an embedded space that represents the perception of a studied attribute. To this end, we propose a set of cost functions and constraints, interpreting trial-wise ordinal relations as distance comparisons in a metric learning task. We tested our proposal on data from two BWS studies investigating the perception of speech social attitudes and timbral qualities. For both datasets, our results show that the structure of the latent space is faithful to human judgements

Carbon Amendments Influence Composition and Functional Capacities of Indigenous Soil Microbiomes

Soil nutrient amendments are recognized for their potential to improve microbial activity and biomass in the soil. However, the specific selective impacts of carbon amendments on indigenous microbiomes and their metabolic functions in agricultural soils remain poorly understood. We investigated the changes in soil chemical characteristics and phenotypes of Streptomyces communities following carbon amendments to soil. Mesocosms were established with soil from two field sites varying in soil organic matter content (low organic matter, LOM; high organic matter, HOM), that were amended at intervals over nine months with low or high dose solutions of glucose, fructose, malic acid, a mixture of these compounds, or water only (non-amended control). Significant shifts in soil chemical characteristics and antibiotic inhibitory capacities of indigenous Streptomyces were observed in response to carbon additions. All high dose carbon amendments consistently increased soil total carbon, while amendments with malic acid decreased soil pH. In LOM soils, higher frequencies of Streptomyces inhibitory phenotypes of the two plant pathogens, Streptomyces scabies and Fusarium oxysporum, were observed in response to soil carbon additions. Additionally, to determine if shifts in Streptomyces functional characteristics correlated with microbiome composition, we investigated whether shifts in functional characteristics of soil Streptomyces correlated with composition of soil bacterial communities, analyzed using 16S rRNA gene sequencing. Regardless of dose, community composition differed significantly among carbon-amended and non-amended soils from both sites. Carbon type and dose had significant effects on bacterial community composition in both LOM and HOM soils. Relationships among microbial community richness (observed species number), diversity, and soil characteristics varied among soils from different sites. These results suggest that manipulation of soil resource availability has the potential to selectively modify the functional capacities of soil microbiomes, and specifically to enhance pathogen inhibitory populations of high value to agricultural systems

Pupil dilation reflects the dynamic integration of audiovisual emotional speech

Emotional speech perception is a multisensory process. When speaking with an individual we concurrently integrate the information from their voice and face to decode e.g., their feelings, moods, and emotions. However, the physiological reactions—such as the reflexive dilation of the pupil—associated to these processes remain mostly unknown. That is the aim of the current article, to investigate whether pupillary reactions can index the processes underlying the audiovisual integration of emotional signals. To investigate this question, we used an algorithm able to increase or decrease the smiles seen in a person’s face or heard in their voice, while preserving the temporal synchrony between visual and auditory channels. Using this algorithm, we created congruent and incongruent audiovisual smiles, and investigated participants’ gaze and pupillary reactions to manipulated stimuli. We found that pupil reactions can reflect emotional information mismatch in audiovisual speech. In our data, when participants were explicitly asked to extract emotional information from stimuli, the first fixation within emotionally mismatching areas (i.e., the mouth) triggered pupil dilation. These results reveal that pupil dilation can reflect the dynamic integration of audiovisual emotional speech and provide insights on how these reactions are triggered during stimulus perception

Peptides encoded by short ORFs control development and define a new eukaryotic gene family

Despite recent advances in developmental biology and in genomics, key questions remain regarding the organisation of cells into embryos. One possibility is that novel types of genes might await discovery and could provide some of the answers. Genome annotation depends strongly on comparison with previously known gene sequences, and so genes having previously uncharacterised structure and function can be missed. Here we present the characterisation of tarsal-less, a new such type of gene. Tarsal-less has two unusual features: first, it contains more than one coding unit, a structure more similar to some bacterial genes. Second, it codes for small peptides rather than proteins, and in fact these peptides represent the smallest gene products known to date. Functional analysis of this gene in the fruitfly Drosophila shows that it has important functions throughout development, including tissue morphogenesis and pattern formation. We identify genes similar to tarsal-less in other species, and thus define a tarsal-less-related gene family. We expect that a combination of bioinformatic and functional methods, such as the ones we use in this study, will identify and characterize more genes of this type. Potentially, thousands of such new genes may exist

Removing Systemic Barriers to Equity, Diversity, and Inclusion: Report of the 2019 Plant Science Research Network Workshop “Inclusivity in the Plant Sciences”

A future in which scientific discoveries are valued and trusted by the general public cannot be achieved without greater inclusion and participation of diverse communities. To envision a path towards this future, in January 2019 a diverse group of researchers, educators, students, and administrators gathered to hear and share personal perspectives on equity, diversity, and inclusion (EDI) in the plant sciences. From these broad perspectives, the group developed strategies and identified tactics to facilitate and support EDI within and beyond the plant science community. The workshop leveraged scenario planning and the richness of its participants to develop recommendations aimed at promoting systemic change at the institutional level through the actions of scientific societies, universities, and individuals and through new funding models to support research and training. While these initiatives were formulated specifically for the plant science community, they can also serve as a model to advance EDI in other disciplines. The proposed actions are thematically broad, integrating into discovery, applied and translational science, requiring and embracing multidisciplinarity, and giving voice to previously unheard perspectives. We offer a vision of barrier-free access to participation in science, and a plant science community that reflects the diversity of our rapidly changing nation, and supports and invests in the training and well-being of all its members. The relevance and robustness of our recommendations has been tested by dramatic and global events since the workshop. The time to act upon them is now

Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study

Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = −0.14; 95% confidence interval [CI]: −0.24 to −0.03; p value = 0.010) and MDD (β = −0.16; 95% CI: −0.27 to −0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34–1.93; p value = 2e−7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD

Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery