Publications

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Background and Aims Iron is essential yet also highly chemically reactive and potentially toxic. The mechanisms that allow cells to use iron safely are not clear; defects in iron management are a causative factor in the cell‐death pathway known as ferroptosis. Poly rC binding protein 1 (PCBP1) is a multifunctional protein that serves as a cytosolic iron chaperone, binding and transferring iron to recipient proteins in mammalian cells. Although PCBP1 distributes iron in cells, its role in managing iron in mammalian tissues remains open for study. The liver is highly specialized for iron uptake, utilization, storage, and secretion. Approach and Results Mice lacking PCBP1 in hepatocytes exhibited defects in liver iron homeostasis with low levels of liver iron, reduced activity of iron enzymes, and misregulation of the cell‐autonomous iron regulatory system. These mice spontaneously developed liver disease with hepatic steatosis, inflammation, and degeneration. Transcriptome analysis indicated activation of lipid biosynthetic and oxidative‐stress response pathways, including the antiferroptotic mediator, glutathione peroxidase type 4. Although PCBP1‐deleted livers were iron deficient, dietary iron supplementation did not prevent steatosis; instead, dietary iron restriction and antioxidant therapy with vitamin E prevented liver disease. PCBP1‐deleted hepatocytes exhibited increased labile iron and production of reactive oxygen species (ROS), were hypersensitive to iron and pro‐oxidants, and accumulated oxidatively damaged lipids because of the reactivity of unchaperoned iron. Conclusions Unchaperoned iron in PCBP1‐deleted mouse hepatocytes leads to production of ROS, resulting in lipid peroxidation (LPO) and steatosis in the absence of iron overload. The iron chaperone activity of PCBP1 is therefore critical for limiting the toxicity of cytosolic iron and may be a key factor in preventing the LPO that triggers the ferroptotic cell‐death pathway.

Abstract Mutations in the QUARTET loci in Arabidopsis result in failure of microspore separation during pollen development due to a defect in degradation of the pollen mother cell wall during late stages of pollen development. Mutations in a new locus required for microspore separation, QRT3, were isolated, and the corresponding gene was cloned by T-DNA tagging. QRT3 encodes a protein that is approximately 30% similar to an endopolygalacturonase from peach (Prunus persica). The QRT3 protein was expressed in yeast (Saccharomyces cerevisiae) and found to exhibit polygalacturonase activity. In situ hybridization experiments showed that QRT3 is specifically and transiently expressed in the tapetum during the phase when microspores separate from their meiotic siblings. Immunohistochemical localization of QRT3 indicated that the protein is secreted from tapetal cells during the early microspore stage. Thus, QRT3 plays a direct role in degrading the pollen mother cell wall during microspore development.

Abstract. Measurements of hyperspectral canopy reflectance provide a detailed snapshot of information regarding canopy biochemistry, structure and physiology. In this study, we collected five years of repeated canopy hyperspectral reflectance measurements for a total of over 100 site visits within the flux footprints of two eddy covariance towers at a pasture and rice paddy in Northern California. The vegetation at both sites exhibited dynamic phenology, with significant inter-annual variability in the timing of seasonal patterns that propagated into inter-annual variability in measured hyperspectral reflectance. We used partial least-squares regression (PLSR) modeling to leverage the information contained within the entire continuous canopy reflectance spectra (400–900 nm) in order to investigate questions regarding the connection between measured hyperspectral reflectance and landscape-scale fluxes of net ecosystem exchange (NEE) and gross primary productivity (GPP) across multiple timescales, from instantaneous flux to monthly-integrated flux. With the PLSR models developed from this large dataset we achieved a high level of predictability for both NEE and GPP flux in these two ecosystems, where the R2 of prediction with an independent validation dataset ranged from 0.24 to 0.69. The PLSR models achieved the highest skill at predicting the integrated GPP flux for the week prior to the hyperspectral canopy reflectance collection, whereas the NEE flux often achieved the same high predictive power at the daily- through monthly-integrated flux timescales. The high level of predictability achieved by PLSR regression in this study demonstrated the potential for using repeated hyperspectral canopy reflectance measurements to help partition NEE measurements into its component fluxes, GPP and ecosystem respiration, and for using continuous hyperspectral reflectance measurements to model regional carbon flux in future analyses.

We report and interpret Hubble Space Telescope (HST) Space Telescope Imaging Spectrograph (STIS) long-slit observations of the optical and ultraviolet (1150-10270 Å) emission line spectra of the rapidly brightening spot 1 on the equatorial ring of SN 1987A between 1997 September and 1999 October (days 3869-4606 after outburst). The emission is caused by radiative shocks created where the supernova blast wave strikes dense gas protruding inward from the equatorial ring. We measure and tabulate line identifications, fluxes, and, in some cases, line widths and shifts. We compute flux correction factors to account for substantial interstellar line absorption of several emission lines. Nebular analysis shows that optical emission lines come from a region of cool (T e ≈ 10 4 K) and dense (n e ≈ 10 6 cm -3) gas in the compressed photoionized layer behind the radiative shock. The observed line widths indicate that only shocks with shock velocities V s < 250 km s -1 have become radiative, while line ratios indicate that much of the emission must have come from yet slower (V s ≲ 135 km s -1) shocks. Such slow shocks can be present only if the protrusion has atomic density n ≳ 3 × 10 4 cm -3, somewhat higher than that of the circumstellar ring. We are able to fit the UV fluxes with an idealized radiative shock model consisting of two shocks (V s = 135 and 250 km s -1). The observed UV flux increase with time can be explained by the increase in shock surface areas as the blast wave overtakes more of the protrusion. The observed flux ratios of optical to highly ionized UV lines are greater by a factor of ∼2-3 than predictions from the radiative shock models, and we discuss the possible causes. We also present models for the observed Ha line widths and profiles, which suggest that a chaotic flow exists in the photoionized regions of these shocks. We discuss what can be learned with future observations of all the spots present on the equatorial ring.

In this paper we present pFabric, a minimalistic datacenter transport design that provides near theoretically optimal flow completion times even at the 99th percentile for short flows, while still minimizing average flow completion time for long flows. Moreover, pFabric delivers this performance with a very simple design that is based on a key conceptual insight: datacenter transport should decouple flow scheduling from rate control. For flow scheduling, packets carry a single priority number set independently by each flow; switches have very small buffers and implement a very simple priority-based scheduling/dropping mechanism. Rate control is also correspondingly simpler; flows start at line rate and throttle back only under high and persistent packet loss. We provide theoretical intuition and show via extensive simulations that the combination of these two simple mechanisms is sufficient to provide near-optimal performance.

In mice, dietary cuprizone causes brain demyelination with subsequent spontaneous remyelination upon return to normal chow. Heavy water (²H₂O) labeling with mass spectrometric analysis can be used to measure brain de novo synthesis of several myelin components including cholesterol, phospholipids, galactocereboside (GalC) and myelin-associated proteins. 24-hydroxycholesterol (24-OHC), the major metabolite of brain cholesterol, is detected in blood and is believed to be specifically derived from CNS cholesterol metabolism. We assessed changes in syntheses of myelin components in brain and of blood sterols during cuprizone-induced experimental demyelination and remyelination, with and without thyroid hormone (T3) treatment. Mice were fed cuprizone for 4 weeks, then returned to control diet and treated with either placebo or T3 (0.005 mg/day). ²H₂O was administered for the last 14 days of cuprizone diet, and for either 6, 12 or 19 days of treatment during recovery from cuprizone, after which blood and corpus callosum (CC) samples were collected (n = 5/time point/treatment). ²H incorporation into cholesterol and 24-OHC in blood and CC, and incorporation into phospholipid (PL)-palmitate, GalC, myelin basic protein (MBP) and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) in CC were measured. Cuprizone significantly (p < 0.05) decreased syntheses of cholesterol, 24-OHC, GalC, MBP, CNPase and PL-palmitate in the CC and these effects were all reversed during recovery. T3 treatment significantly (p < 0.05) increased syntheses of cholesterol, 24-OHC and palmitate compared to placebo. 24-OHC and cholesterol turnover rates in brain and blood were nearly identical and 24-OHC rates in blood paralleled rates in CC, indicating that blood 24-OHC derives primarily from the brain and reflects oligodendrocyte function. In summary, changes in synthesis of several lipid and protein components in brain during cuprizone-induced demyelination and remyelination are measurable through stable isotope labeling. Blood 24-OHC turnover rates closely reflect flux rates of brain cholesterol in response to cuprizone and T3, which alter oligodendrocyte function. Labeling of blood 24-OHC has potential as a non-invasive marker of brain de novo cholesterol synthesis and breakdown rates in demyelinating conditions.

Monolithic materials have quickly become a well-established stationary phase format in the field of capillary electrochromatography (CEC). Both the simplicity of their in situ preparation method and the large variety of readily available chemistries make the monolithic separation media an attractive alternative to capillary columns packed with particulate materials. This review summarizes the contributions of numerous groups working in this rapidly growing area, with a focus on monolithic capillary columns prepared from synthetic polymers. Various approaches employed for the preparation of the monoliths are detailed, and where available, the material properties of the resulting monolithic capillary columns are shown. Their chromatographic performance is demonstrated by numerous separations of different analyte mixtures in variety of modes. Although detailed studies of the effect of polymer properties on the analytical performance of monolithic capillaries remain scarce at this early stage of their development, this review also discusses some important relationships such as the effect of pore size on the separation performance in more detail.