Decentering Anthropocentrisms: A Functional Approach to Animal Minds

Anthropocentric biases manifest themselves in two different ways in research on animal cognition. Some researchers claim that only humans have the capacity for reasoning, beliefs, and interests; and others attribute mental concepts to nonhuman animals on the basis of behavioral evidence, and they conceive of animal cognition in more or less human terms. Both approaches overlook the fact that language-use deeply informs mental states, such that comparing human mental states to the mental states of nonlinguistic animals is misguided. In order to avoid both pitfalls -- assuming that animals have mental lives just like we do, or assuming that they have no mental lives at all -- I argue for a functional methodological approach. Researchers should study animal cognition by identifying environmental inputs, the functional role of internal states, and behavioral outputs. Doing so will allow for cross-species comparisons in a way that the use of folk psychological terms does not

Fichte’s Practical Response to the Problem of Other Minds

The present paper examines the problem of attributing mental predicates to anyone but myself. Traditionally, this has been a major issue at the intersection of epistemology and ethics, because whether we should consider someone in our moral deliberations is often thought to depend on their cognitive abilities or their capacity for consciousness. For both Kant and Fichte, we have direct moral duties only to other rational beings. The fact that the other is present to us as a representation (for Kant) or as a Not-I that is posited in opposition to the I (for Fichte) threatens our supposed moral obligations to them and risks a form of metaphysical solipsism and moral egoism. The bindingness of interpersonal obligations depends on overcoming the separation between me and other persons. It will be shown that in order to establish the other as a morally considerable being, Fichte reverses the direction of implication: I do not derive my moral duties from others’ personhood; rather, others’ personhood follows from my immediate sense of moral obligation toward them. The way that the problem of other minds is posed presupposes that the only appropriate answer would be a series of propositions that establishes the existence of other morally considerable beings outside of myself. The immediate moral feeling of considerability, however, is not a proposition. It will be argued that Fichte thus provides a radically different alternative to Kant’s approach. The problem of other minds is not answered or solved but is rather dispelled in Fichte’s philosophy by the feeling of moral obligation and the recognition of others as the object of our obligations

Interplay between Microorganisms and Geochemistry in Geological Carbon Storage

Citation: Kirk, MF, Altman, SJ, Santillan, EFU, Bennett, PC (2016) Interplay between microorganisms and geochemistry in geological carbon storage. International Journal of Greenhouse Gas Control 47, 386-395.Researchers at the Center for Frontiers of Subsurface Energy Security (CFSES) have conducted laboratory and modeling studies to better understand the interplay between microorganisms and geochemistry for geological carbon storage (GCS). We provide evidence of microorganisms adapting to high pressure CO2 conditions and identify factors that may influence survival of cells to CO2 stress. Factors that influenced the ability of cells to survive exposure to high-pressure CO2 in our experiments include mineralogy, the permeability of cell walls and/or membranes, intracellular buffering capacity, and whether cells live planktonically or within biofilm. Column experiments show that, following exposure to acidic water, biomass can remain intact in porous media and continue to alter hydraulic conductivity. Our research also shows that geochemical changes triggered by CO2 injection can alter energy available to populations of subsurface anaerobes and that microbial feedbacks on this effect can influence carbon storage. Our research documents the impact of CO2 on microorganisms and in turn, how subsurface microorganisms can influence GCS. We conclude that microbial presence and activities can have important implications for carbon storage and that microorganisms should not be overlooked in further GCS research

Whole animal experiments should be more like human randomized controlled trials

Beverly S. Muhlhausler, Frank H. Bloomfield, Matthew W. Gillma

A modular framework for the development of targeted Covid-19 blood transcript profiling panels

Covid-19 morbidity and mortality are associated with a dysregulated immune response. Tools are needed to enhance existing immune profiling capabilities in affected patients. Here we aimed to develop an approach to support the design of targeted blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection.; We designed a pool of candidates based on a pre-existing and well-characterized repertoire of blood transcriptional modules. Available Covid-19 blood transcriptome data was also used to guide this process. Further selection steps relied on expert curation. Additionally, we developed several custom web applications to support the evaluation of candidates.; As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: immunological relevance, therapeutic development relevance and SARS biology relevance.; Altogether the work presented here may contribute to the future expansion of immune profiling capabilities via targeted profiling of blood transcript abundance in Covid-19 patients

Multi-omic association study identifies DNA methylation-mediated genotype and smoking exposure effects on lung function in children living in urban settings

Impaired lung function in early life is associated with the subsequent development of chronic respiratory disease. Most genetic associations with lung function have been identified in adults of European descent and therefore may not represent those most relevant to pediatric populations and populations of different ancestries. In this study, we performed genome-wide association analyses of lung function in a multiethnic cohort of children (n = 1,035) living in low-income urban neighborhoods. We identified one novel locus at the TDRD9 gene in chromosome 14q32.33 associated with percent predicted forced expiratory volume in one second (FEV1) (p = 2.4x10-9; βz = -0.31, 95% CI = -0.41- -0.21). Mendelian randomization and mediation analyses revealed that this genetic effect on FEV1 was partially mediated by DNA methylation levels at this locus in airway epithelial cells, which were also associated with environmental tobacco smoke exposure (p = 0.015). Promoter-enhancer interactions in airway epithelial cells revealed chromatin interaction loops between FEV1-associated variants in TDRD9 and the promoter region of the PPP1R13B gene, a stimulator of p53-mediated apoptosis. Expression of PPP1R13B in airway epithelial cells was significantly associated the FEV1 risk alleles (p = 1.3x10-5; β = 0.12, 95% CI = 0.06–0.17). These combined results highlight a potential novel mechanism for reduced lung function in urban youth resulting from both genetics and smoking exposure

Inducible expression quantitative trait locus analysis of the MUC5AC gene in asthma in urban populations of children

BACKGROUND: Mucus plugging can worsen asthma control, lead to reduced lung function and fatal exacerbations. MUC5AC is the secretory mucin implicated in mucus plugging, and MUC5AC gene expression has been associated with development of airway obstruction and asthma exacerbations in urban children with asthma. However, the genetic determinants of MUC5AC expression are not established. OBJECTIVE: To assess single-nucleotide polymorphisms (SNPs) that influence MUC5AC expression and relate to pulmonary functions in childhood asthma. METHODS: We used RNA-sequencing data from upper airway samples and performed cis-expression quantitative trait loci (eQTL) and allele specific expression (ASE) analyses in two cohorts of predominantly Black and Hispanic urban children, a high asthma-risk birth cohort and an exacerbation-prone asthma cohort. We further investigated inducible MUC5AC eQTLs during incipient asthma exacerbations. We tested significant eQTLs SNPs for associations with lung function measurements and investigated their functional consequences in DNA regulatory databases. RESULTS: We identified two independent groups of SNPs in the MUC5AC gene that were significantly associated with MUC5AC expression. Moreover, these SNPs showed stronger eQTL associations with MUC5AC expression during asthma exacerbations, consistent with inducible expression. SNPs in one group also showed significant association with decreased pulmonary functions. These SNPs included multiple EGR1 transcription factor binding sites suggesting a mechanism of effect. CONCLUSIONS: These findings demonstrate the applicability of organ specific RNA-sequencing data to determine genetic factors contributing to a key disease pathway. Specifically, they suggest important genetic variations that may underlie propensity to mucus plugging in asthma and could be important in targeted asthma phenotyping and disease management strategies

Asthma-associated genetic variants induce IL33 differential expression through an enhancer-blocking regulatory region

Genome-wide association studies (GWAS) have implicated the IL33 locus in asthma, but the underlying mechanisms remain unclear. Here, we identify a 5 kb region within the GWAS-defined segment that acts as an enhancer-blocking element in vivo and in vitro. Chromatin conformation capture showed that this 5 kb region loops to the IL33 promoter, potentially regulating its expression. We show that the asthma-associated single nucleotide polymorphism (SNP) rs1888909, located within the 5 kb region, is associated with IL33 gene expression in human airway epithelial cells and IL-33 protein expression in human plasma, potentially through differential binding of OCT-1 (POU2F1) to the asthma-risk allele. Our data demonstrate that asthma-associated variants at the IL33 locus mediate allele-specific regulatory activity and IL33 expression, providing a mechanism through which a regulatory SNP contributes to genetic risk of asthma.This work was supported by NIH grants R01 HL118758, R01 HL128075, R01 HL119577, R01 HL085197, U19 AI095230, UG3 OD023282 and UM1 AI114271

Development of a fixed module repertoire for the analysis and interpretation of blood transcriptome data.

As the capacity for generating large-scale molecular profiling data continues to grow, the ability to extract meaningful biological knowledge from it remains a limitation. Here, we describe the development of a new fixed repertoire of transcriptional modules, BloodGen3, that is designed to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome data. The construction of this repertoire is based on co-clustering patterns observed across sixteen immunological and physiological states encompassing 985 blood transcriptome profiles. Interpretation is supported by customized resources, including module-level analysis workflows, fingerprint grid plot visualizations, interactive web applications and an extensive annotation framework comprising functional profiling reports and reference transcriptional profiles. Taken together, this well-characterized and well-supported transcriptional module repertoire can be employed for the interpretation and benchmarking of blood transcriptome profiles within and across patient cohorts. Blood transcriptome fingerprints for the 16 reference cohorts can be accessed interactively via: https://drinchai.shinyapps.io/BloodGen3Module/