Non-pigmented rapidly growing mycobacteria are nontuberculous mycobacteria (NTM) capable of producing disease. We report a case of tattoo-associated NTM infection with a novel species: Mycobacterium mageritense. A 48-year-old man presented with a two-week history of a papulopustular eruption on the shaded areas of a tattoo that had been placed five weeks prior while in the Philippines. Histopathology from punch biopsies revealed suppurative granulomatous dermatitis with acid fast bacilli present. Subsequent matrix assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometer identified the bacteria as Mycobacterium margeritense. After consultation with infectious disease specialists and culture susceptibilities, the patient was treated with three months of dual antibiotic therapy with minocycline and moxifloxacin. The patient experienced a slow but complete resolution of clinical skin findings after the course of treatment. Since discovery in 1997, M. mageritense infection has been demonstrated in a wide spectrum of disease, predominantly skin and soft tissue infections. The species has not been previously implicated in tattoo-associated NTM infections. M. mageritense should be considered as a specific type of mycobacteria in the differential diagnosis for tattoo-associated NTM infections owing to differences in antibiotic susceptibilities compared to other NTM species.

Development of complex neural circuits like the peripheral somatosensory system requires intricate mechanisms to ensure axons make proper connections. While much is known about ligand-receptor pairs required for dorsal root ganglion (DRG) axon guidance, very little is known about the cytoplasmic effectors that mediate cellular responses triggered by these guidance cues. Here we show that members of the Cas family of cytoplasmic signaling adaptors are highly phosphorylated in central projections of the DRG as they enter the spinal cord. Furthermore, we provide genetic evidence that Cas proteins regulate fasciculation of DRG sensory projections. These data establish an evolutionarily conserved requirement for Cas adaptor proteins during peripheral nervous system axon pathfinding. They also provide insight into the interplay between axonal fasciculation and adhesion to the substrate.

Immature astrocytes and blood vessels enter the developing mammalian retina at the optic nerve head and migrate peripherally to colonize the entire retinal nerve fiber layer (RNFL). Retinal vascularization is arrested in retinopathy of prematurity (ROP), a major cause of bilateral blindness in children. Despite their importance in normal development and ROP, the factors that control vascularization of the retina remain poorly understood. Because astrocytes form a reticular network that appears to provide a substrate for migrating endothelial cells, they have long been proposed to guide angiogenesis. However, whether astrocytes do in fact impose a spatial pattern on developing vessels remains unclear, and how astrocytes themselves are guided is unknown. Here we explore the cellular mechanisms that ensure complete retinal coverage by astrocytes and blood vessels in mouse. We find that migrating astrocytes associate closely with the axons of retinal ganglion cells (RGCs), their neighbors in the RNFL. Analysis of Robo1; Robo2 mutants, in which RGC axon guidance is disrupted, and Math5 (Atoh7) mutants, which lack RGCs, reveals that RGCs provide directional information to migrating astrocytes that sets them on a centrifugal trajectory. Without this guidance, astrocytes exhibit polarization defects, fail to colonize the peripheral retina, and display abnormal fine-scale spatial patterning. Furthermore, using cell type-specific chemical-genetic tools to selectively ablate astrocytes, we show that the astrocyte template is required for angiogenesis and vessel patterning. Our results are consistent with a model whereby RGC axons guide formation of an astrocytic network that subsequently directs vessel development.

Meiotic recombination rates can vary widely across genomes, with hotspots ofintense activity interspersed among cold regions. In yeast, hotspots tend to occur inpromoter regions of genes, whereas in humans and mice hotspots are largely definedby binding sites of the PRDM9 protein. To investigate the detailed recombinationpattern in a flowering plant we use shotgun resequencing of a wild population of themonkeyflower Mimulus guttatus to precisely locate over 400,000 boundaries ofhistoric crossovers or gene conversion tracts. Their distribution defines some 13,000hotspots of varying strengths, interspersed with cold regions of undetectably lowrecombination. Average recombination rates peak near starts of genes and fall offsharply, exhibiting polarity. Within genes, recombination tracts are more likely toterminate in exons than in introns. The general pattern is similar to that observed inyeast, as well as in PRDM9-knockout mice, suggesting that recombination initiationdescribed here in Mimulus may reflect ancient and conserved eukaryoticmechanisms

The mature mammalian cortex is composed of 6 architecturally and functionally distinct layers. Two key steps in the assembly of this layered structure are the initial establishment of the glial scaffold and the subsequent migration of postmitotic neurons to their final position. These processes involve the precise and timely regulation of adhesion and detachment of neural cells from their substrates. Although much is known about the roles of adhesive substrates during neuronal migration and the formation of the glial scaffold, less is understood about how these signals are interpreted and integrated within these neural cells. Here, we provide in vivo evidence that Cas proteins, a family of cytoplasmic adaptors, serve a functional and redundant role during cortical lamination. Cas triple conditional knock-out (Cas TcKO) mice display severe cortical phenotypes that feature cobblestone malformations. Molecular epistasis and genetic experiments suggest that Cas proteins act downstream of transmembrane Dystroglycan and β1-Integrin in a radial glial cell-autonomous manner. Overall, these data establish a new and essential role for Cas adaptor proteins during the formation of cortical circuits and reveal a signaling axis controlling cortical scaffold formation.

The timing and mechanisms of past hydroclimate change in northeast Mexico are poorly constrained, limiting our ability to evaluate climate model performance. To address this, we present a multiproxy speleothem record of past hydroclimate variability spanning 62.5 to 5.1 ka from Tamaulipas, Mexico. Here we show a strong influence of Atlantic and Pacific sea surface temperatures on orbital and millennial scale precipitation changes in the region. Multiple proxies show no clear response to insolation forcing, but strong evidence for dry conditions during Heinrich Stadials. While these trends are consistent with other records from across Mesoamerica and the Caribbean, the relative importance of thermodynamic and dynamic controls in driving this response is debated. An isotope-enabled climate model shows that cool Atlantic SSTs and stronger easterlies drive a strong inter-basin sea surface temperature gradient and a southward shift in moisture convergence, causing drying in this region.

Reconstructing hydroclimate over the Common Era is essential for understanding the dominant mechanisms of precipitation change and improving climate model projections, which currently suggest Northeast Mexico will become drier in the future. Tree-ring reconstructions have suggested regional rainfall is primarily controlled by Pacific sea-surface temperatures (SSTs). However, tree ring records tend to reflect winter-spring rainfall, and thus may not accurately record total annual precipitation. Using the first multiproxy speleothem record spanning the last millennium, combined with results from an atmospheric general circulation model, we demonstrate mean annual rainfall in Northeast Mexico is highly sensitive to Atlantic SST variability. Our findings suggest future precipitation in Northeast Mexico is more dependent upon the warming of Tropical Atlantic SSTs relative to the Tropical Pacific.

The immune system comprises a complex network of specialized cells that protects against infection, eliminates cancerous cells, and regulates tissue repair, thus serving a critical role in homeostasis, health span, and life span. The subterranean-dwelling naked mole-rat (NM-R; Heterocephalus glaber) exhibits prolonged life span relative to its body size, is unusually cancer resistant, and manifests few physiological or molecular changes with advancing age. We therefore hypothesized that the immune system of NM-Rs evolved unique features that confer enhanced cancer immunosurveillance and prevent the age-associated decline in homeostasis. Using single-cell RNA-sequencing (scRNA-seq) we mapped the immune system of the NM-R and compared it to that of the short-lived, cancer-prone mouse. In contrast to the mouse, we find that the NM-R immune system is characterized by a high myeloid-to-lymphoid cell ratio that includes a novel, lipopolysaccharide (LPS)-responsive, granulocyte cell subset. Surprisingly, we also find that NM-Rs lack canonical natural killer (NK) cells. Our comparative genomics analyses support this finding, showing that the NM-R genome lacks an expanded gene family that controls NK cell function in several other species. Furthermore, we reconstructed the evolutionary history that likely led to this genomic state. The NM-R thus challenges our current understanding of mammalian immunity, favoring an atypical, myeloid-biased mode of innate immunosurveillance, which may contribute to its remarkable health span.

Cave carbonate minerals are an important terrestrial paleoclimate archive. A few studies have explored the potential for applying carbonate clumped isotope thermometry to speleothems as a tool for constraining past temperatures. To date, most papers utilizing this method have focused on mass-47 clumped isotope values (Δ47) at a single location and reported that cave carbonate minerals rarely achieve isotopic equilibrium, with kinetic isotope effects (KIEs) attributed to CO2 degassing. More recently, studies have shown that mass-47 and mass-48 CO2 from acid digested carbonate minerals (Δ47 and Δ48) can be used together to assess equilibrium and probe KIEs. Here, we examined 44 natural and synthetic modern cave carbonate mineral samples from 13 localities with varying environmental conditions (ventilation, water level, pCO2, temperature) for (dis)equilibrium using Δ47-Δ48 values, in concert with traditional stable carbon (δ13C) and oxygen (δ18O) isotope ratios. Data showed that 19 of 44 samples exhibited Δ47-Δ48 values indistinguishable from isotopic equilibrium, and 18 (95 %) of these samples yield Δ47-predicted temperatures within error of measured modern temperatures. Conversely, 25 samples exhibited isotopic disequilibria, 13 of which yield erroneous temperature estimates. Within some speleothem samples, we find Δ47-Δ48 values consistent with CO2 degassing effects, however, the majority of samples with KIEs are consistent with other processes being dominant. We hypothesize that these values reflect isotopic buffering effects on clumped isotopes that can be considerable and cannot be overlooked. Using a Raleigh Distillation Model, we examined carbon and oxygen isotope exchange trajectories and their relationships with dual clumped isotope disequilibria. Carbon isotope exchange is associated with depletion of both Δ47 and Δ48 relative to equilibrium, while oxygen isotope exchange is associated with enrichment of both Δ47 and Δ48 relative to equilibrium. Cave rafts collected from proximate locations in Mexico exhibit the largest average departures from equilibrium (ΔΔ47¯ = −0.032 ± 0.007, ΔΔ48¯ = −0.104 ± 0.035, where ΔΔi is the measured value – the equilibrium value). This study shows how the Δ47-Δ48 dual carbonate clumped isotope framework can be applied to a variety of tcave carbonate mineral samples, enabling identification of isotopic equilibria and therefore quantitative application of clumped isotope thermometry for paleoclimate reconstruction, or alternatively, constraining the mechanisms of kinetic effects.