An Atypical Presentation of a Rare Disease

A 76-year-old white woman presented for evaluation of asymptomatic skin lesions on her right shin, right buttock, and left arm. All lesions initially underwent slow growth and plateaued and then remained stable in size. A complete review of systems revealed normal results. She had 3 well-demarcated erythematous round plaques ranging from 1.5 to 3 cm, all with a central depression, yellow hue, and prominent telangiectasias (Figs 1 and 2). An excisional biopsy was performed. Histologically, there were palisading granulomas within the papillary and reticular dermis, predominantly composed of a histiocytic cell population with multiple large giant cells (S100-; Fig 3)

Pervasively anoxic surface conditions at the onset of the Great Oxidation Event: new multi-proxy constraints from the Cooper Lake paleosol

Oceanic element inventories derived from marine sedimentary rocks place important constraints on oxidative continental weathering in deep time, but there remains a scarcity in complementary observations directly from continental sedimentary reservoirs. This study focuses on better defining continental weathering conditions near the Archean-Proterozoic boundary through the multi-proxy (major and ultra-trace element, Fe and Cr stable isotopes, μ-XRF elemental mapping, and detrital zircon U-Pb geochronology) investigation of the ca. 2.45 billion year old (giga annum, Ga) Cooper Lake paleosol (saprolith), developed on a sediment-hosted mafic dike within the Huronian Supergroup (Ontario, Canada). Throughout the variably altered Cooper Lake saprolith, ratios of immobile elements (Nb, Ta, Zr, Hf, Th, Al, Ti) are constant, indicating a uniform pre-alteration dike composition, lack of extreme pH weathering conditions, and no major influence from ligand-rich fluids during weathering or burial metasomatism/metamorphism. The loss of Mg, Fe, Na, Sr, and Li, a signature of albite and ferromagnesian silicate weathering, increases towards the top of the preserved profile (unconformity) and dike margins. Coupled bulk rock behaviour of Fe-Mg-Mn and co-localization of Fe- Mn in clay minerals (predominantly chlorite) indicates these elements were solubilized primarily in their divalent state without Fe/Mn-oxide formation. A lack of a Ce anomaly and immobility of Mo, V, and Cr further support pervasively anoxic weathering conditions. Subtle U enrichment is the only geochemical evidence, if primary, that could be consistent with oxidative element mobilization. The leaching of ferromagnesian silicates was accompanied by variable mobility and depletion of transition metals with a relative depletion order of Fe≈Mg≈Zn\u3eNi\u3eCo\u3eCu (Cu being significantly influenced by secondary sulfide formation). Mild enrichment of heavy Fe isotopes (δ56/54Fe from 0.169 to 0.492 ‰) correlating with Fe depletion in the saprolith indicates loss of isotopically light aqueous Fe(II). Minor REE+Y fractionation with increasing alteration intensity, including a decreasing Eu anomaly and Y/Ho ratio, is attributed to albite breakdown and preferential scavenging of HREE\u3eY by clay minerals, respectively. Younger metasomatism resulted in the addition of several elements (K, Rb, Cs, Be, Tl, Ba, Sn, In, W), partly or wholly obscuring their earlier paleo-weathering trends. The behavior of Cr at Cooper Lake can help test previous hypotheses of an enhanced, low pH-driven continental weathering flux of Cr(III) to marine reservoirs between ca. 2.48-2.32 Ga and the utility of the stable Cr isotope proxy of Mn-oxide induced Cr(III) oxidation. Synchrotron μ- XRF maps and invariant Cr/Nb ratios reveal complete immobility of Cr despite its distribution amongst both clay-rich groundmass and Fe-Ti oxides. Assuming a pH-dependent, continental source of Cr(III) to marine basins, the Cr immobility at Cooper Lake indicates either that signatures of acidic surface waters were localized to uppermost and typically unpreserved regolith horizons or were geographically restricted to acid-generating point sources. However, in given detrital pyrite preservation in fluvial sequences overlying the paleosol, we propose that the oxidative sulphide corrosion required to drive surface pH(δ53/52Cr: -0.321 ± 0.038 ‰, 2sd, n=34) that cannot be linked to Cr(III) oxidation and is instead interpreted to have a magmatic origin. The combined chemical signatures and continued preservation of detrital pyrite/uraninite indicate low atmospheric O2 during weathering at ca. 2.45 Ga preserved in the rift-related sedimentary rocks of the Lower Huronian. The aqueous flux from the reduced weathering of mafic rocks was characterized by a greater abundance of transition metals (Fe, Mn, Zn, Co, Ni) with isotopically light Fe(II), as well as higher Eu/Eu* and Y/Ho. In most models of Precambrian ocean element inventories, hydrothermal fluids are viewed as the main supplier of several metals (e.g., Fe, Zn), although the results herein suggest that a riverine metal supply may have been substantial and that using Eu-excess as a strict proxy for hydrothermal flux may be misleading in near-shore marine sedimentary environments

A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay

4E-transporter (4E-T) is one of several proteins that bind the mRNA 5′cap-binding protein, eukaryotic initiation factor 4E (eIF4E), through a conserved binding motif. We previously showed that 4E-T is a nucleocytoplasmic shuttling protein, which mediates the import of eIF4E into the nucleus. At steady state, 4E-T is predominantly cytoplasmic and is concentrated in bodies that conspicuously resemble the recently described processing bodies (P-bodies), which are believed to be sites of mRNA decay. In this paper, we demonstrate that 4E-T colocalizes with mRNA decapping factors in bona fide P-bodies. Moreover, 4E-T controls mRNA half-life, because its depletion from cells using short interfering RNA increases mRNA stability. The 4E-T binding partner, eIF4E, also is localized in P-bodies. 4E-T interaction with eIF4E represses translation, which is believed to be a prerequisite for targeting of mRNAs to P-bodies. Collectively, these data suggest that 4E-T interaction with eIF4E is a priming event in inducing messenger ribonucleoprotein rearrangement and transition from translation to decay

Depth-dependent δ13 C trends in platform and slope settings of the Campbellrand-Malmani carbonate platform and possible implications for Early Earth oxygenation

Highlights • Carbon cycle of Neoarchean carbonate platform and potential oxygen oasis. • Carbon isotopes reveal a shift to aerobic biosphere and increasing oxidation state. • Rare earth element patterns reveal decrease in open ocean water influx. • Rimmed margin architecture was crucial for evolution of aerobic ecosystems. Abstract The evolution of oxygenic photosynthesis is widely seen as the major biological factor for the profound shift from reducing to slightly oxidizing conditions in Earth’s atmosphere during the Archean-Proterozoic transition period. The delay from the first biogenic production of oxygen and the permanent oxidation of Earth’s atmosphere during the early Paleoproteorozoic Great Oxidation Event (GOE) indicates that significant environmental modifications were necessary for an effective accumulation of metabolically produced oxygen. Here we report a distinct temporal shift to heavier carbon isotope signatures in lagoonal and intertidal carbonates (δ13Ccarb from -1.6 to +0.2 ‰, relative to VPDB) and organic matter (δ13Corg from about -40 to -25 ‰, relative to VPDB) from the 2.58–2.50 Gy old shallow–marine Campbellrand-Malmani carbonate platform (South Africa). This indicates an increase in the burial rate of organic matter caused by enhanced primary production as well as a change from an anaerobic to an aerobic ecosystem. Trace element data indicate limited influx of reducing species from deep open ocean water into the platform and an increased supply of nutrients from the continent, both supporting primary production and an increasing oxidation state of the platform interior. These restricted conditions allowed that the dissolved inorganic carbon (DIC) pool in the platform interior developed differently than the open ocean. This is supported by coeval carbonates from the marginal slope setting, which had a higher interaction with open ocean water and do not record a comparable shift in δ13Ccarb throughout the sequence. We propose that the emergence of stable shallow-water carbonate platforms in the Neoarchean provided ideal conditions for the evolution of early aerobic ecosystems, which finally led to the full oxidation of Earth’s atmosphere during the GOE

Public social media consultations for dermatologic conditions: an online survey

The use of social media in medicine has been increasingly studied in recent years, especially concerning its role in patient outreach, education, diagnosis, and management. Dermatology is a unique field in that patients can post photographs of their skin ailments when seeking online medical advice and information. This study examines the role of public social media consultations for dermatologic conditions. A large portion of patients utilize social media for dermatologic consultations and many do not seek care from a dermatologist afterward. Future studies should trend this phenomenon, especially as the use of social media continues to expand

Iron Isotope Fractionation during Fe(II) Oxidation Mediated by the Oxygen-Producing Marine Cyanobacterium Synechococcus PCC 7002

In this study, we couple iron isotope analysis to microscopic and mineralogical investigation of iron speciation during circumneutral Fe(II) oxidation and Fe(III) precipitation with photosynthetically produced oxygen. In the presence of the cyanobacterium Synechococcus PCC 7002, aqueous Fe(II) (Fe(II)aq) is oxidized and precipitated as amorphous Fe(III) oxyhydroxide minerals (iron precipitates, Feppt), with distinct isotopic fractionation (ε56Fe) values determined from fitting the δ56Fe(II)aq (1.79‰ and 2.15‰) and the δ56Feppt (2.44‰ and 2.98‰) data trends from two replicate experiments. Additional Fe(II) and Fe(III) phases were detected using microscopy and chemical extractions and likely represent Fe(II) and Fe(III) sorbed to minerals and cells. The iron desorbed with sodium acetate (FeNaAc) yielded heavier δ56Fe compositions than Fe(II)aq. Modeling of the fractionation during Fe(III) sorption to cells and Fe(II) sorption to Feppt, combined with equilibration of sorbed iron and with Fe(II)aq using published fractionation factors, is consistent with our resulting δ56FeNaAc. The δ56Feppt data trend is inconsistent with complete equilibrium exchange with Fe(II)aq. Because of this and our detection of microbially excreted organics (e.g., exopolysaccharides) coating Feppt in our microscopic analysis, we suggest that electron and atom exchange is partially suppressed in this system by biologically produced organics. These results indicate that cyanobacteria influence the fate and composition of iron in sunlit environments via their role in Fe(II) oxidation through O2 production, the capacity of their cell surfaces to sorb iron, and the interaction of secreted organics with Fe(III) minerals

DHX34 and NBAS form part of an autoregulatory NMD circuit that regulates endogenous RNA targets in human cells, zebrafish and Caenorhabditis elegans

The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons but also regulates the abundance of cellular RNAs. We sought to identify transcripts that are regulated by two novel NMD factors, DHX34 and neuroblastoma amplified sequence (NBAS), which were identified in a genome-wide RNA interference screen in Caenorhabditis elegans and later shown to mediate NMD in vertebrates. We performed microarray expression profile analysis in human cells, zebrafish embryos and C. elegans that were individually depleted of these factors. Our analysis revealed that a significant proportion of genes are co-regulated by DHX34, NBAS and core NMD factors in these three organisms. Further analysis indicates that NMD modulates cellular stress response pathways and membrane trafficking across species. Interestingly, transcripts encoding different NMD factors were sensitive to DHX34 and NBAS depletion, suggesting that these factors participate in a conserved NMD negative feedback regulatory loop, as was recently described for core NMD factors. In summary, we find that DHX34 and NBAS act in concert with core NMD factors to co-regulate a large number of endogenous RNA targets. Furthermore, the conservation of a mechanism to tightly control NMD homeostasis across different species highlights the importance of the NMD response in the control of gene expression

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data