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Type III IFN lambdas (IFN-λ) have recently been described as important mediators of immune responses at barrier surfaces. However, their role in autoimmune diseases such as systemic lupus erythematosus (SLE), a condition characterized by aberrant type I IFN signaling, has not been determined. Here, we identify a nonredundant role for IFN-λ in immune dysregulation and tissue inflammation in a model of TLR7-induced lupus. IFN-λ protein is increased in murine lupus and IFN-λ receptor (Ifnlr1) deficiency significantly reduces immune cell activation and associated organ damage in the skin and kidneys without effects on autoantibody production. Single-cell RNA sequencing in mouse spleen and human peripheral blood revealed that only mouse neutrophils and human B cells are directly responsive to this cytokine. Rather, IFN-λ activates keratinocytes and mesangial cells to produce chemokines that induce immune cell recruitment and promote tissue inflammation. These data provide insights into the immunobiology of SLE and identify type III IFNs as important factors for tissue-specific pathology in this disease.Blooms of Zygnematophycean "glacier algae" lower the bare ice albedo of the Greenland Ice Sheet (GrIS), amplifying summer energy absorption at the ice surface and enhancing meltwater runoff from the largest cryospheric contributor to contemporary sea-level rise. Here, we provide a step change in current understanding of algal-driven ice sheet darkening through quantification of the photophysiological mechanisms that allow glacier algae to thrive on and darken the bare ice surface. Significant secondary phenolic pigmentation (11 times the cellular content of chlorophyll a) enables glacier algae to tolerate extreme irradiance (up to ∼4,000 µmol photons⋅m-2⋅s-1) while simultaneously repurposing captured ultraviolet and short-wave radiation for melt generation. Total cellular energy absorption is increased 50-fold by phenolic pigmentation, while glacier algal chloroplasts positioned beneath shading pigments remain low-light-adapted (E k ∼46 µmol photons⋅m-2⋅s-1) and dependent upon typical nonphotochemical quenching mechanisms for photoregulation. On the GrIS, glacier algae direct only ∼1 to 2.4% of incident energy to photochemistry versus 48 to 65% to ice surface melting, contributing an additional ∼1.86 cm water equivalent surface melt per day in patches of high algal abundance (∼104 cells⋅mL-1). At the regional scale, surface darkening is driven by the direct and indirect impacts of glacier algae on ice albedo, with a significant negative relationship between broadband albedo (Moderate Resolution Imaging Spectroradiometer [MODIS]) and glacier algal biomass (R 2 = 0.75, n = 149), indicating that up to 75% of the variability in albedo across the southwestern GrIS may be attributable to the presence of glacier algae. Copyright © 2020 the Author(s). selleck chemicals Published by PNAS.Unlike other snakes, most species of Rhabdophis possess glands in their dorsal skin, sometimes limited to the neck, known as nucho-dorsal and nuchal glands, respectively. Those glands contain powerful cardiotonic steroids known as bufadienolides, which can be deployed as a defense against predators. Bufadienolides otherwise occur only in toads (Bufonidae) and some fireflies (Lampyrinae), which are known or believed to synthesize the toxins. The ancestral diet of Rhabdophis consists of anuran amphibians, and we have shown previously that the bufadienolide toxins of frog-eating species are sequestered from toads consumed as prey. However, one derived clade, the Rhabdophis nuchalis Group, has shifted its primary diet from frogs to earthworms. Here we confirm that the worm-eating snakes possess bufadienolides in their nucho-dorsal glands, although the worms themselves lack such toxins. In addition, we show that the bufadienolides of R. nuchalis Group species are obtained primarily from fireflies. Although few snakes feed on insects, we document through feeding experiments, chemosensory preference tests, and gut contents that lampyrine firefly larvae are regularly consumed by these snakes. Furthermore, members of the R. nuchalis Group contain compounds that resemble the distinctive bufadienolides of fireflies, but not those of toads, in stereochemistry, glycosylation, acetylation, and molecular weight. Thus, the evolutionary shift in primary prey among members of the R. nuchalis Group has been accompanied by a dramatic shift in the source of the species' sequestered defensive toxins. Copyright © 2020 the Author(s). Published by PNAS.Insect nervous systems offer unique advantages for studying interactions between sensory systems and behavior, given their complexity with high tractability. By examining the neural coding of salient environmental stimuli and resulting behavioral output in the context of environmental stressors, we gain an understanding of the effects of these stressors on brain and behavior and provide insight into normal function. The implication of neonicotinoid (neonic) pesticides in contributing to declines of nontarget species, such as bees, has motivated the development of new compounds that can potentially mitigate putative resistance in target species and declines of nontarget species. We used a neuroethologic approach, including behavioral assays and multineuronal recording techniques, to investigate effects of imidacloprid (IMD) and the novel insecticide sulfoxaflor (SFX) on visual motion-detection circuits and related escape behavior in the tractable locust system. Despite similar LD50 values, IMD and SFX evoked different behavioral and physiological effects. IMD significantly attenuated collision avoidance behaviors and impaired responses of neural populations, including decreases in spontaneous firing and neural habituation. In contrast, SFX displayed no effect at a comparable sublethal dose. These results show that neonics affect population responses and habituation of a visual motion detection system. We propose that differences in the sublethal effects of SFX reflect a different mode of action than that of IMD. More broadly, we suggest that neuroethologic assays for comparative neurotoxicology are valuable tools for fully addressing current issues regarding the proximal effects of environmental toxicity in nontarget species. Copyright © 2020 the Author(s). Published by PNAS.A 2009 report by the National Academy of Sciences was highly critical of many forensic practices. This report concluded that significant changes and advances were required to ensure the reliability across the forensic sciences. We examine the reliability of one such forensic technique used for identification based on purported distinct patterns on the seams of denim pants. Although first proposed more than 20 years ago, no thorough analysis of reliability or reproducibility of this forensic technique has previously been reported. We performed a detailed analysis of this forensic technique to determine its reliability and efficacy. Copyright © 2020 the Author(s). Published by PNAS.Commonly used methods for estimating parameters of a spatial dynamic panel data model include the two-stage least squares, quasi-maximum likelihood, and generalized moments. In this paper, we present an approach that uses the eigenvalues and eigenvectors of a spatial weight matrix to directly construct consistent least-squares estimators of parameters of a general spatial dynamic panel data model. The proposed methodology is conceptually simple and efficient and can be easily implemented. We show that the proposed parameter estimators are consistent and asymptotically normally distributed under mild conditions. We demonstrate the superior performance of our approach via extensive simulation studies. We also provide a real data example.Although aerobic respiration is a hallmark of eukaryotes, a few unicellular lineages, growing in hypoxic environments, have secondarily lost this ability. In the absence of oxygen, the mitochondria of these organisms have lost all or parts of their genomes and evolved into mitochondria-related organelles (MROs). There has been debate regarding the presence of MROs in animals. Using deep sequencing approaches, we discovered that a member of the Cnidaria, the myxozoan Henneguya salminicola, has no mitochondrial genome, and thus has lost the ability to perform aerobic cellular respiration. This indicates that these core eukaryotic features are not ubiquitous among animals. Our analyses suggest that H. salminicola lost not only its mitochondrial genome but also nearly all nuclear genes involved in transcription and replication of the mitochondrial genome. In contrast, we identified many genes that encode proteins involved in other mitochondrial pathways and determined that genes involved in aerobic respiration or mitochondrial DNA replication were either absent or present only as pseudogenes. As a control, we used the same sequencing and annotation methods to show that a closely related myxozoan, Myxobolus squamalis, has a mitochondrial genome. The molecular results are supported by fluorescence micrographs, which show the presence of mitochondrial DNA in M. squamalis, but not in H. salminicola. Our discovery confirms that adaptation to an anaerobic environment is not unique to single-celled eukaryotes, but has also evolved in a multicellular, parasitic animal. Hence, H. salminicola provides an opportunity for understanding the evolutionary transition from an aerobic to an exclusive anaerobic metabolism.Regulation of gene expression is critical for Mycobacterium tuberculosis to tolerate stressors encountered during infection, and for non-pathogenic mycobacteria such as Mycobacterium smegmatis to survive environmental stressors. Unlike better-studied models, mycobacteria express ∼14% of their genes as leaderless transcripts. However, the impacts of leaderless transcript structures on mRNA half-life and translation efficiency in mycobacteria have not been directly tested. For leadered transcripts, the contributions of 5' UTRs to mRNA half-life and translation efficiency are similarly unknown. In M. tuberculosis and M. smegmatis, the essential sigma factor, SigA, is encoded by a transcript with a relatively short half-life. We hypothesized that sigA's long 5' UTR causes this instability. To test this, we constructed fluorescence reporters and measured protein abundance, mRNA abundance, and mRNA half-life, and calculated relative transcript production rates. The sigA 5' UTR conferred an increased transcript prodnters. Understanding how M. link2 tuberculosis regulates gene expression may provide clues for ways to interfere with the bacterium's survival. Gene expression encompasses transcription, mRNA degradation, and translation. Here we used Mycobacterium smegmatis as a model organism to study how 5' untranslated regions affect these three facets of gene expression in multiple ways. We furthermore provide insight into the expression of leaderless mRNAs, which lack 5' untranslated regions and are unusually prevalent in mycobacteria. link3 Copyright © 2020 Nguyen et al.In bacteria, chromosomal DNA resides in the cytoplasm, and most transcription factors are also found in the cytoplasm. However, some transcription factors, called membrane-bound transcription factors (MTFs), reside in the cytoplasmic membrane. Here, we report the identification of a new MTF in the Gram-positive pathogen Staphylococcus aureus and its regulation by the protease FtsH. The MTF, named MbtS (Membrane-bound transcription factor of Staphylococcus aureus), is encoded by SAUSA300_2640 and predicted to have an N-terminal DNA binding domain and three transmembrane helices. The MbtS protein was degraded by the membrane vesicles containing FtsH or by the purified FtsH. MbtS bound to an inverted repeat sequence in its promoter region, and the DNA binding was essential for its transcription. Transcriptional comparison between the ftsH-deletion mutant and the ftsH/mbtS double mutant showed that MbtS could alter the transcription of over 200 genes. Although the MbtS protein was not detected in WT cells grown in a liquid medium, the protein was detected in some isolated colonies on an agar plate.