Open Access Publications from the University of California

### Recent Work

UC Research Initiatives supports multicampus research teams, partners UC and national laboratory scientists, and advances innovations that benefit California.

## The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading

(2018)

© 2018 The Author(s). Pex1 and Pex6 form a heterohexameric motor essential for peroxisome biogenesis and function, and mutations in these AAA-ATPases cause most peroxisome-biogenesis disorders in humans. The tail-anchored protein Pex15 recruits Pex1/Pex6 to the peroxisomal membrane, where it performs an unknown function required for matrix-protein import. Here we determine that Pex1/Pex6 from S. cerevisiae is a protein translocase that unfolds Pex15 in a pore-loop-dependent and ATP-hydrolysis-dependent manner. Our structural studies of Pex15 in isolation and in complex with Pex1/Pex6 illustrate that Pex15 binds the N-terminal domains of Pex6, before its C-terminal disordered region engages with the pore loops of the motor, which then processively threads Pex15 through the central pore. Furthermore, Pex15 directly binds the cargo receptor Pex5, linking Pex1/Pex6 to other components of the peroxisomal import machinery. Our results thus support a role of Pex1/Pex6 in mechanical unfolding of peroxins or their extraction from the peroxisomal membrane during matrix-protein import.

## Manganese-Driven Carbon Oxidation at Oxic-Anoxic Interfaces

(2018)

Copyright © 2018 American Chemical Society. The formation of reactive manganese (Mn) species is emerging as a key regulator of carbon oxidation rates, and thus CO2 emissions, in soils and sediments. Many subsurface environments are characterized by steep oxygen gradients, forming oxic-anoxic interfaces that enable rapid redox cycling of Mn. Here, we examined the impact of Mn(II)aq oxidation along oxic-anoxic interfaces on carbon oxidation in soils using laboratory-based diffusion reactors. A combination of cyclic voltammetry, X-ray absorption spectroscopy, and X-ray microprobe imaging revealed a tight coupling between Mn(II)aq oxidation and carbon oxidation at the oxic-anoxic interface. Specifically, zones of Mn(II)aq oxidation across the oxic-anoxic transition also exhibited the greatest lignin oxidation potential, carbon solubilization, and oxidation. Microprobe imaging further revealed that the generation of Mn(III)-dominated precipitates coincided with carbon oxidation. Combined, our findings demonstrate that biotic Mn(II)aq oxidation, specifically the formation of Mn(III) species, contributes to carbon oxidation along oxic-anoxic interfaces in soils and sediments. Our results suggest that we should regard carbon oxidation not merely as a function of molecular composition, which insufficiently predicts rates, but in relation to microenvironments favoring the formation of critically important oxidants such as Mn(III).

## Direct-coupled micro-magnetometer with Y-Ba-Cu-O nano-slit SQUID fabricated with a focused helium ion beam

(2018)

© 2018 Author(s). Direct write patterning of high-transition temperature (high-TC) superconducting oxide thin films with a focused helium ion beam is a formidable approach for the scaling of high-TC circuit feature sizes down to the nanoscale. In this letter, we report using this technique to create a sensitive micro superconducting quantum interference device (SQUID) magnetometer with a sensing area of about 100 × 100 μm2. The device is fabricated from a single 35-nm thick YBa2Cu3O7-δ film. A flux concentrating pick-up loop is directly coupled to a 10 nm × 20 μm nano-slit SQUID. The SQUID is defined entirely by helium ion irradiation from a gas field ion source. The irradiation converts the superconductor to an insulator, and no material is milled away or etched. In this manner, a very narrow non-superconducting nano-slit is created entirely within the plane of the film. The narrow slit dimension allows for maximization of the coupling to the field concentrator. Electrical measurements reveal a large 0.35 mV modulation with a magnetic field. We measure a white noise level of 2 μΦ0/Hz12. The field noise of the magnetometer is 4 pT/Hz12 at 4.2 K.

## The Persistence of Population III Star Formation

(2018)

We present a semi-analytic model of star formation in the early universe, beginning with the first metal-free stars. By employing a completely feedback-limited star formation prescription, stars form at maximum efficiency until the self-consistently calculated feedback processes halt formation. We account for a number of feedback processes including a meta-galactic Lyman-Werner background, supernovae, photoionization, and chemical feedback. Halos are evolved combining mass accretion rates found through abundance matching with our feedback-limited star formation prescription, allowing for a variety of Population III (Pop III) initial mass functions (IMFs). We find that, for a number of models, massive Pop III star formation can continue on until at least $z \sim 20$ and potentially past $z \sim 6$ at rates of around $10^{-4}$ to $10^{-5}$ M$_\odot$ yr$^{-1}$ Mpc$^{-3}$, assuming these stars form in isolation. At this point Lyman-Werner feedback pushes the minimum halo mass for star formation above the atomic cooling threshold, cutting off the formation of massive Pop III stars. We find that, in most models, Pop II and Pop III star formation co-exist over cosmological time-scales, with the total star formation rate density and resulting radiation background strongly dominated by the former before Pop III star formation finally ends. These halos form at most $\sim 10^3$ M$_\odot$ of massive Pop III stars during this phase and typically have absolute magnitudes in the range of $M_\text{AB} = -5$ to $-10$. We also briefly discuss how future observations from telescopes such as JWST or WFIRST and 21-cm experiments may be able to constrain unknown parameters in our model such as the IMF, star formation prescription, or the physics of massive Pop III stars.

## Estimating evapotranspiration change due to forest treatment and fire at the basin scale in the Sierra Nevada, California

(2018)

We investigated the potential magnitude and duration of forest evapotranspiration (ET) decreases resulting from forest-thinning treatments and wildfire in west-slope watersheds of the Sierra Nevada range in California, U.S.A. using a robust empirical relation between Landsat-derived mean-annual normalized difference vegetation index (NDVI) and ET measured at flux towers. Among forest treatments, the minimum observed NDVI change required to produce a significant departure from control plots with NDVI of about 0.70 was -0.09 units, corresponding to a basal-area reduction of 29.1 m2 ha-1 (45% reduction) and equivalent to an estimated ET reduction of 153 mm yr-1 (21% change; approximate mean annual precipitation = 1000 mm). Intensive thinning in highly productive forests that approached pre-fire-exclusion densities reduced basal area by 40-50%, generating estimated ET reductions of 153-218 mm yr-1 (21-27% change) over five years following treatment. Low-intensity underburn treatments resulted in no significant change in ET. Examining the cumulative impact of wildfires on ET between 1990 and 2008, we found that the lower and wetter American River basin (5310 km2) generated more than twice the ET reduction per unit area than those in the higher and drier Kings River basin (4790 km2), corresponding to greater water and energy limitations in the latter and greater fire severity in the former. A rough extrapolation of these results to the entire American River watershed suggests that ET reductions due to forest thinning by wildfire could approach 10% of full natural flows for dry years and 5% over all years.

(2018)

## Natural variation in the multidrug efflux pump SGE1 underlies ionic liquid tolerance in yeast

(2018)

© 2018 by the Genetics Society of America. Imidazolium ionic liquids (IILs) have a range of biotechnological applications, including as pretreatment solvents that extract cellulose from plant biomass for microbial fermentation into sustainable bioenergy. However, residual levels of IILs, such as 1-ethyl-3-methylimidazolium chloride ([C2C1im]Cl), are toxic to biofuel-producing microbes, including the yeast Saccharomyces cerevisiae. S. cerevisiae strains isolated from diverse ecological niches differ in genomic sequence and in phenotypes potentially beneficial for industrial applications, including tolerance to inhibitory compounds present in hydrolyzed plant feedstocks. We evaluated >100 genome-sequenced S. cerevisiae strains for tolerance to [C2C1im]Cl and identified one strain with exceptional tolerance. By screening a library of genomic DNA fragments from the [C2C1im]Cl-tolerant strain for improved IIL tolerance, we identified SGE1, which encodes a plasma membrane multidrug efflux pump, and a previously uncharacterized gene that we named ionic liquid tolerance 1 (ILT1), which encodes a predicted membrane protein. Analyses of SGE1 sequences from our panel of S. cerevisiae strains together with growth phenotypes implicated two single nucleotide polymorphisms (SNPs) that associated with IIL tolerance and sensitivity. We confirmed these phenotypic effects by transferring the SGE1 SNPs into a [C2 C1 im]Cl-sensitive yeast strain using CRISPR/Cas9 genome editing. Further studies indicated that these SNPs affect Sge1 protein stability and cell surface localization, influencing the amount of toxic IILs that cells can pump out of the cytoplasm. Our results highlight the general potential for discovering useful biotechnological functions from untapped natural sequence variation and provide functional insight into emergent SGE1 alleles with reduced capacities to protect against IIL toxicity.

## Plasma fatty acid ethanolamides are associated with postprandial triglycerides, ApoCIII, and ApoE in humans consuming a high-fructose corn syrup-sweetened beverage

(2018)

© 2018 the American Physiological Society. Epidemiological and clinical research studies have provided ample evidence demonstrating that consumption of sugar-sweetened beverages increases risk factors involved in the development of obesity, Type 2 diabetes, and cardiovascular disease (CVD). Our previous study demonstrated that when compared with aspartame (Asp), 2 wk of high-fructose corn syrup (HFCS)-sweetened beverages provided at 25% of daily energy requirement was associated with increased body weight, postprandial (pp) triglycerides (TG), and fasting and pp CVD risk factors in young adults. The fatty acid ethanolamide, anandamide (AEA), and the monoacylglycerol, 2-arachidonoyl-sn-glycerol (2-AG), are two primary endocannabinoids (ECs) that play a role in regulating food intake, increasing adipose storage, and regulating lipid metabolism. Therefore, we measured plasma concentrations of ECs and their analogs, oleoylethanolamide (OEA), docosahexaenoyl ethanolamide (DHEA), and docosahexaenoyl glycerol (DHG), in participants from our previous study who consumed HFCS-or Asp-sweetened beverages to determine associations with weight gain and CVD risk factors. Two-week exposure to either HFCS-or Asp-sweetened beverages resulted in significant differences in the changes in fasting levels of OEA and DHEA between groups after the testing period. Subjects who consumed Asp, but not HFCS, displayed a reduction in AEA, OEA, and DHEA after the testing period. In contrast, there were significant positive relationships between AEA, OEA, and DHEA vs. ppTG, ppApoCIII, and ppApoE in those consuming HFCS, but not in those consuming Asp. Our findings reveal previously unknown associations between circulating ECs and EC-related molecules with markers of lipid metabolism and CVD risk after HFCS consumption.

(2018)

## Stochastic Block Models are a Discrete Surface Tension

(2018)

Networks, which represent agents and interactions between them, arise in myriad applications throughout the sciences, engineering, and even the humanities. To understand large-scale structure in a network, a common task is to cluster a network's nodes into sets called "communities" such that there are dense connections within communities but sparse connections between them. A popular and statistically principled method to perform such clustering is to use a family of generative models known as stochastic block models (SBMs). In this paper, we show that maximum likelihood estimation in an SBM is a network analog of a well-known continuum surface-tension problem that arises from an application in metallurgy. To illustrate the utility of this bridge, we implement network analogs of three surface-tension algorithms, with which we successfully recover planted community structure in synthetic networks and which yield fascinating insights on empirical networks from the field of hyperspectral video segmentation.