Resolving the neural circuits of anxiety

Although anxiety disorders represent a major societal problem demanding new therapeutic targets, these efforts have languished in the absence of a mechanistic understanding of this subjective emotional state. While it is impossible to know with certainty the subjective experience of a rodent, rodent models hold promise in dissecting well-conserved limbic circuits. The application of modern approaches in neuroscience has already begun to unmask the neural circuit intricacies underlying anxiety by allowing direct examination of hypotheses drawn from existing psychological concepts. This information points toward an updated conceptual model for what neural circuit perturbations could give rise to pathological anxiety and thereby provides a roadmap for future therapeutic development.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (NIH Director’s New Innovator Award DP2-DK-102256-01)National Institute of Mental Health (U.S.) (NIH) R01-MH102441-01)JPB Foundatio

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Synthesis of earthworm trace metal uptake and bioaccumulation data: role of soil concentration, earthworm ecophysiology, and experimental design

Trace metals can be essential for organo-metallic structures and oxidation-reduction in metabolic processes or may cause acute or chronic toxicity at elevated concentrations. The uptake of trace metals by earthworms can cause transfer from immobilized pools in the soil to predators within terrestrial food chains. We report a synthesis and evaluation of uptake and bioaccumulation empirical data across different metals, earthworm genera, ecophysiological groups, soil properties, and experimental conditions (metal source, uptake duration, soil extraction method). Peer-reviewed datasets were extracted from manuscripts published before June 2019. The 56 studies contained 3513 soil-earthworm trace metal concentration paired data sets across 11 trace metals (As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Sb, U, Zn). Across all field and laboratory experiments studied, the median concentrations of Hg, Pb, and Cd in earthworm tissues that were above concentrations known to be hazardous for consumption by small mammals and avian predators but not for Cu, Zn, Cr, Ni, and As. Power regressions show only Hg and Cd earthworm tissue concentrations were well-correlated with soil concentrations with R2 > 0.25. However, generalized linear mixed-effect models reveal that earthworm concentrations were significantly correlated with soil concentrations for log-transformed Hg, Cd, Cu, Zn, As, Sb (p < 0.05). Factors that significantly contributed to these relationships included earthworm genera, ecophysiological group, soil pH, and organic matter content. Moreover, spiking soils with metal salts, shortening the duration of exposure, and measuring exchangeable soil concentrations resulted in significantly higher trace metal uptake or greater bioaccumulation factors. Our results highlight that earthworms are able to consistently bioaccumulate toxic metals (Hg and Cd only) across field and laboratory conditions. However, future experiments should incorporate greater suites of trace metals, broader genera of earthworms, and more diverse laboratory and field settings to generate data to devise universal quantitative relationships between soil and earthworm tissue concentrations