Now showing items 3022-3041 of 11675

    • The E3 ubiquitin ligase MARCH1 regulates glucose-tolerance and lipid storage in a sex-specific manner

      Bhagwandin, Candida; Ashbeck, Erin L; Whalen, Michael; Bandola-Simon, Joanna; Roche, Paul A; Szajman, Adam; Truong, Sarah Mai; Wertheim, Betsy C; Klimentidis, Yann C; Ishido, Satoshi; et al. (PUBLIC LIBRARY SCIENCE, 2018-10-24)
      Type 2 diabetes is typified by insulin-resistance in adipose tissue, skeletal muscle, and liver, leading to chronic hyperglycemia. Additionally, obesity and type 2 diabetes are characterized by chronic low-grade inflammation. Membrane-associated RING-CH-1 (MARCH1) is an E3 ubiquitin ligase best known for suppression of antigen presentation by dendritic and B cells. MARCH1 was recently found to negatively regulate the cell surface levels of the insulin receptor via ubiquitination. This, in turn, impaired insulin sensitivity in mouse models. Here, we report that MARCH1-deficient (knockout; KO) female mice exhibit excessive weight gain and excessive visceral adiposity when reared on standard chow diet, without increased inflammatory cell infiltration of adipose tissue. By contrast, male MARCH1 KO mice had similar weight gain and visceral adiposity to wildtype (WT) male mice. MARCH1 KO mice of both sexes were more glucose tolerant than WT mice. The levels of insulin receptor were generally higher in insulin-responsive tissues (especially the liver) from female MARCH1 KO mice compared to males, with the potential to account in part for the differences between male and female MARCH1 KO mice. We also explored a potential role for MARCH1 in human type 2 diabetes risk through genetic association testing in publicly-available datasets, and found evidence suggestive of association. Collectively, our data indicate an additional link between immune function and diabetes, specifically implicating MARCH1 as a regulator of lipid metabolism and glucose tolerance, whose function is modified by sex-specific factors.
    • Earlier snowmelt reduces atmospheric carbon uptake in midlatitude subalpine forests

      Winchell, Taylor S.; Barnard, David M.; Monson, Russell K.; Burns, Sean P.; Molotch, Noah P.; Univ Arizona, Dept Ecol & Evolutionary Biol; Univ Arizona, Tree Ring Res Lab; Institute of Alpine and Arctic Research; University of Colorado Boulder; Boulder Colorado USA; Institute of Alpine and Arctic Research; University of Colorado Boulder; Boulder Colorado USA; Department of Ecology and Evolutionary Biology and Laboratory for Tree Ring Research; University of Arizona; Tucson Arizona USA; et al. (AMER GEOPHYSICAL UNION, 2016-08-16)
      Previous work demonstrates conflicting evidence regarding the influence of snowmelt timing on forest net ecosystem exchange (NEE). Based on 15years of eddy covariance measurements in Colorado, years with earlier snowmelt exhibited less net carbon uptake during the snow ablation period, which is a period of high potential for productivity. Earlier snowmelt aligned with colder periods of the seasonal air temperature cycle relative to later snowmelt. We found that the colder ablation-period air temperatures during these early snowmelt years lead to reduced rates of daily NEE. Hence, earlier snowmelt associated with climate warming, counterintuitively, leads to colder atmospheric temperatures during the snow ablation period and concomitantly reduced rates of net carbon uptake. Using a multilinear-regression (R-2=0.79, P<0.001) relating snow ablation period mean air temperature and peak snow water equivalent (SWE) to ablation-period NEE, we predict that earlier snowmelt and decreased SWE may cause a 45% reduction in midcentury ablation-period net carbon uptake.
    • Early AMD-like defects in the RPE and retinal degeneration in aged mice with RPE-specific deletion of Atg5 or Atg7

      Zhang, Youwen; Cross, Samuel D.; Stanton, James B.; Marmorstein, Alan D.; Le, Yun Zheng; Marmorstein, Lihua Y.; Univ Arizona, Dept Ophthalmol & Vis Sci (MOLECULAR VISION, 2017-04-14)
      Purpose: To examine the effects of autophagy deficiency induced by RPE-specific deletion of Atg5 or Atg7 in mice as a function of age. Methods: Conditional knockout mice with a floxed allele of Atg5 or Atg7 were crossed with inducible VMD2-rtTA/Cre transgenic mice. VMD2-directed RPE-specific Cre recombinase expression was induced with doxycycline feeding in the resulting mice. Cre-mediated deletion of floxed Atg5 or Atg7 resulted in RPE-specific inactivation of the Atg5 or Atg7 gene. Plastic and thin retinal sections were analyzed with light and electron microscopy for histological changes. Photoreceptor outer segment (POS) thickness in plastic sections was measured using the Adobe Photoshop CS4 extended ruler tool. Autophagic adaptor p62/SQSTM1 and markers for oxidatively damaged lipids, proteins, and DNA were examined with immunofluorescence staining of cryosections. Fluorescence signals were quantified using Image J software. Results: Accumulation of p62/SQSTM1 reflecting autophagy deficiency was observed in the RPE of the Atg5(Delta RPE) and Atg7(Delta RP)E mice. 3-nitrotyrosine, advanced glycation end products (AGEs), and 8-hydroxy-2'-deoxyguanosine (8-OHdG), markers for oxidatively damaged proteins and DNA, were also found to accumulate in the RPE of these mice. We observed retinal degeneration in 35% of the Atg5(Delta RPE) mice and 45% of the Atg7.RPE mice at 8 to 24 months old. Degeneration severity and the number of mice with degeneration increased with age. The mean POS thickness of these mice was 25 mu m at 8-12 months, 15 mu m at 13-18 months, and 3 mu m at 19-24 months, compared to 35 mu m, 30 mu m, and 24 aem in the wildtype mice, respectively. Early age-related macular degeneration (AMD)-like RPE defects were found in all the Atg5(Delta RPE) and Atg7.RPE mice 13 months old or older, including vacuoles, uneven RPE thickness, diminished basal infoldings, RPE hypertrophy/hypotrophy, pigmentary irregularities, and necrosis. The severity of the RPE defects increased with age and in the mice with retinal degeneration. RPE atrophy and choroidal neovascularization (CNV) were occasionally observed in the Atg5(Delta RPE) and Atg7(Delta RPE) mice with advanced age. Conclusions: Autophagy deficiency induced by RPE-specific deletion of Atg5 or Atg7 predisposes but does not necessarily drive the development of AMD-like phenotypes or retinal degeneration.
    • Early and Persistent Dendritic Hypertrophy in the Basolateral Amygdala following Experimental Diffuse Traumatic Brain Injury

      Hoffman, Ann N.; Paode, Pooja R.; May, Hazel G.; Ortiz, J. Bryce; Kemmou, Salma; Lifshitz, Jonathan; Conrad, Cheryl D.; Currier Thomas, Theresa; Department of Child Health, University of Arizona College of Medicine-Phoenix (MARY ANN LIEBERT, INC, 2017-01)
      In the pathophysiology of traumatic brain injury (TBI), the amygdala remains understudied, despite involvement in processing emotional and stressful stimuli associated with anxiety disorders, such as post-traumatic stress disorder (PTSD). Because the basolateral amygdala (BLA) integrates inputs from sensory and other limbic structures coordinating emotional learning and memory, injury-induced changes in circuitry may contribute to psychiatric sequelae of TBI. This study quantified temporal changes in dendritic complexity of BLA neurons after experimental diffuse TBI, modeled by midline fluid percussion injury. At post-injury days (PIDs) 1, 7, and 28, brain tissue from sham and brain-injured adult, male rats was processed for Golgi, glial fibrillary acidic protein (GFAP), or silver stain and analyzed to quantify BLA dendritic branch intersections, activated astrocytes, and regional neuropathology, respectively. Compared to sham, brain-injured rats at all PIDs showed enhanced dendritic branch intersections in both pyramidal and stellate BLA neuronal types, as evidenced by Sholl analysis. GFAP staining in the BLA was significantly increased at PID1 and 7 in comparison to sham. However, the BLA was relatively spared from neuropathology, demonstrated by an absence of argyrophilic accumulation over time, in contrast to other brain regions. These data suggest an early and persistent enhancement of dendritic complexity within the BLA after a single diffuse TBI. Increased dendritic complexity would alter information processing into and through the amygdala, contributing to emotional symptoms post-TBI, including PTSD.
    • The Early Detection and Follow-up of the Highly Obscured Type II Supernova 2016ija/DLT16am

      Tartaglia, L.; Sand, David J.; Valenti, S.; Wyatt, S.; Anderson, J. P.; Arcavi, I.; Ashall, C.; Botticella, M. T.; Cartier, R.; Chen, T.-W.; et al. (IOP PUBLISHING LTD, 2018-01-23)
      We present our analysis of the Type II supernova DLT16am (SN 2016ija). The object was discovered during the ongoing D < 40 Mpc (DLT40) one-day cadence supernova search at r similar to 20.1 mag in the "edge-on" nearby (D = 20.0 +/- 4.0 Mpc) galaxy NGC 1532. The subsequent prompt and high-cadenced spectroscopic and photometric follow-up revealed a highly extinguished transient, with E(B - V) = 1.95 +/- 0.15 mag, consistent with a standard extinction law with R-V = 3.1 and a bright (M-V = -18.48 +/- 0.77 mag) absolute peak magnitude. A comparison of the photometric features with those of large samples of SNe II reveals a fast rise for the derived luminosity and a relatively short plateau phase, with a slope of S-50V = 0.84 +/- 0.04 mag/50 days, consistent with the photometric properties typical of those of fast-declining SNe II. Despite the large uncertainties on the distance and the extinction in the direction of DLT16am, the measured photospheric expansion velocity and the derived absolute V-band magnitude at similar to 50 days after the explosion match the existing luminosity-velocity relation for SNe II.
    • Early detection of ovarian cancer using the risk of ovarian cancer algorithm with frequent CA125 testing in women at increased familial risk-combined results from two screening trials

      Skates, Steven J; Greene, Mark H.; Buys, Saundra S; Mai, Phuong L; Brown, Powel; Piedmonte, Marion; Rodriguez, Gustavo; Schorge, John O; Sherman, Mark; Daly, Mary B; et al. (American Association for Cancer Research, 2017-01-31)
      Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6-12 monthly CA125>35U/mL. Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject’s baseline, which triggered transvaginal ultrasound. Specificity and PPV were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls.
    • Early diabetes impairs ON sustained ganglion cell light responses and adaptation without cell death or dopamine insensitivity

      Flood, Michael D; Wellington, Andrea J; Cruz, Luis A; Eggers, Erika D; Univ Arizona, Dept Physiol; Univ Arizona, Dept Biomed Engn (ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2020-09-08)
      Retinal signaling under dark-adapted conditions is perturbed during early diabetes. Additionally, dopamine, the main neuromodulator of retinal light adaptation, is diminished in diabetic retinas. However, it is not known if this dopamine deficiency changes how the retina responds to increased light or dopamine. Here we determine whether light adaptation is impaired in the diabetic retina, and investigate potential mechanism(s) of impairment. Diabetes was induced in C57BL/6J male mice via 3 intraperitoneal injections of streptozotocin (75 mg/kg) and confirmed by blood glucose levels more than 200 mg/dL. After 6 weeks, whole-cell recordings of light-evoked and spontaneous inhibitory postsynaptic currents (IPSCs) or excitatory postsynaptic currents (EPSCs) were made from rod bipolar cells and ON sustained ganglion cells, respectively. Light responses were recorded before and after D1 receptor (D1R) activation (SKF-38393, 20 μM) or light adaptation (background of 950 photons·μm-2 ·s-1). Retinal whole mounts were stained for either tyrosine hydroxylase and activated caspase-3 or GAD65/67, GlyT1 and RBPMS and imaged. D1R activation and light adaptation both decreased inhibition, but the disinhibition was not different between control and diabetic rod bipolar cells. However, diabetic ganglion cell light-evoked EPSCs were increased in the dark and showed reduced light adaptation. No differences were found in light adaptation of spontaneous EPSC parameters, suggesting upstream changes. No changes in cell density were found for dopaminergic, glycinergic or GABAergic amacrine cells, or ganglion cells. Thus, in early diabetes, ON sustained ganglion cells receive excessive excitation under dark- and light-adapted conditions. Our results show that this is not attributable to loss in number or dopamine sensitivity of inhibitory amacrine cells or loss of dopaminergic amacrine cells.
    • The Early Discovery of SN 2017ahn: Signatures of Persistent Interaction in a Fast-declining Type II Supernova

      Tartaglia, L.; Sand, D. J.; Groh, J. H.; Valenti, S.; Wyatt, S. D.; Bostroem, K. A.; Brown, P. J.; Yang, S.; Burke, J.; Chen, T.-W.; et al. (IOP Publishing Ltd, 2021-01-28)
      We present high-cadence, comprehensive data on the nearby (D; 33 Mpc) Type II supernova (SN II) 2017ahn, discovered within about one day of the explosion, from the very early phases after explosion to the nebular phase. The observables of SN 2017ahn show a significant evolution over the;470 days of our follow-up campaign, first showing prominent, narrow Balmer lines and other high-ionization features purely in emission (i.e., flash spectroscopy features), which progressively fade and lead to a spectroscopic evolution similar to that of more canonical SNe II. Over the same period, the decline of the light curves in all bands is fast, resembling the photometric evolution of linearly declining H-rich core-collapse SNe. The modeling of the light curves and early flash spectra suggests that a complex circumstellar medium surrounds the progenitor star at the time of explosion, with a first dense shell produced during the very late stages of its evolution that is swept up by the rapidly expanding ejecta within the first ∼6 days of the SN evolution, while signatures of interaction are observed also at later phases. Hydrodynamical models support the scenario in which linearly declining SNe II are predicted to arise from massive yellow super- or hypergiants depleted of most of their hydrogen layers. © 2021. The American Astronomical Society. All rights reserved.
    • Early for Everyone: Reconceptualizing Palliative Care in the Neonatal Intensive Care Unit

      Quinn, Megan; Weiss, Alyssa B; Crist, Janice D; Univ Arizona, Coll Nursing (LIPPINCOTT WILLIAMS & WILKINS, 2020-04)
      Background: Palliative care (PC) in the neonatal intensive care unit (NICU) is often provided exclusively to infants expected to die. Standards of care support providing PC early after diagnosis with any condition likely to impact quality of life. Purpose: To determine the state of early PC practice across populations to derive elements of early PC applicable to neonates and their families and demonstrate their application in practice. Search Strategy: Multiple literature searches were conducted from 2016 to 2019. Common keywords used were: palliative care; early PC; end of life, neonate; NICU; perinatal PC; pediatric PC; family-centered care; advanced care planning; palliative care consultant; and shared decision-making. Findings: Early PC is an emerging practice in adult, pediatric, and perinatal populations that has been shown to be helpful for and recommended by families. Three key elements of early PC in the NICU are shared decision-making, care planning, and coping with distress. A hypothetical case of a 24-week infant is presented to illustrate how findings may be applied. Evidence supports expansion of neonatal PC to include infants and families without terminal diagnoses and initiation earlier in care.
    • Early High-contrast Imaging Results with Keck/NIRC2-PWFS: The SR 21 Disk

      Uyama, T.; Ren, B.; Mawet, D.; Ruane, G.; Bond, C.Z.; Hashimoto, J.; Liu, M.C.; Muto, T.; Ruffio, J.-B.; Wallack, N.; et al. (IOP Publishing Ltd, 2020)
      High-contrast imaging of exoplanets and protoplanetary disks depends on wave front sensing and correction made by adaptive optics instruments. Classically, wave front sensing has been conducted at optical wavelengths, which made high-contrast imaging of red targets such as M-type stars or extincted T Tauri stars challenging. Keck/NIRC2 has combined near-infrared (NIR) detector technology with the pyramid wave front sensor (PWFS). With this new module we observed SR 21, a young star that is brighter at NIR wavelengths than at optical wavelengths. Compared with the archival data of SR 21 taken with the optical wave front sensing we achieved ∼20% better Strehl ratio in similar natural seeing conditions. Further post-processing utilizing angular differential imaging and reference-star differential imaging confirmed the spiral feature reported by the Very Large Telescope/Spectro-Polarimetric High-contrast Exoplanet REsearch instrument polarimetric observation, which is the first detection of the SR 21 spiral in total intensity at L′ band. We also compared the contrast limit of our result (10-4 at 0.″4 and 2 10-5 at 1.″0) with the archival data that were taken with optical wave front sensing and confirmed the improvement, particularly at ≤0.″5. Our observation demonstrates that the NIR PWFS improves AO performance and will provide more opportunities for red targets in the future. © 2020. The American Astronomical Society. All rights reserved..
    • Early High-contrast Imaging Results with Keck/NIRC2-PWFS: The SR 21 Disk

      Uyama, Taichi; Ren, Bin; Mawet, Dimitri; Ruane, Garreth; Bond, Charlotte Z.; Hashimoto, Jun; Liu, Michael C.; Muto, Takayuki; Ruffio, Jean-Baptiste; Wallack, Nicole; et al. (IOP PUBLISHING LTD, 2020-11-23)
      High-contrast imaging of exoplanets and protoplanetary disks depends on wave front sensing and correction made by adaptive optics instruments. Classically, wave front sensing has been conducted at optical wavelengths, which made high-contrast imaging of red targets such as M-type stars or extincted T Tauri stars challenging. Keck/NIRC2 has combined near-infrared (NIR) detector technology with the pyramid wave front sensor (PWFS). With this new module we observed SR 21, a young star that is brighter at NIR wavelengths than at optical wavelengths. Compared with the archival data of SR 21 taken with the optical wave front sensing we achieved similar to 20% better Strehl ratio in similar natural seeing conditions. Further post-processing utilizing angular differential imaging and reference-star differential imaging confirmed the spiral feature reported by the Very Large Telescope/Spectro-Polarimetric High-contrast Exoplanet REsearch instrument polarimetric observation, which is the first detection of the SR 21 spiral in total intensity at L ' band. We also compared the contrast limit of our result (10(-4) at 04 and 2 x 10(-5) at 10) with the archival data that were taken with optical wave front sensing and confirmed the improvement, particularly at <= 05. Our observation demonstrates that the NIR PWFS improves AO performance and will provide more opportunities for red targets in the future.
    • Early human impacts and ecosystem reorganization in southern-central Africa

      Thompson, J.C.; Wright, D.K.; Ivory, S.J.; Choi, J.-H.; Nightingale, S.; Mackay, A.; Schilt, F.; Otárola-Castillo, E.; Mercader, J.; Forman, S.L.; et al. (American Association for the Advancement of Science, 2021)
      Modern Homo sapiens engage in substantial ecosystem modification, but it is difficult to detect the origins or early consequences of these behaviors. Archaeological, geochronological, geomorphological, and paleoenvironmental data from northern Malawi document a changing relationship between forager presence, ecosystem organization, and alluvial fan formation in the Late Pleistocene. Dense concentrations of Middle Stone Age artifacts and alluvial fan systems formed after ca. 92 thousand years ago, within a paleoecological context with no analog in the preceding half-million-year record. Archaeological data and principal coordinates analysis indicate that early anthropogenic fire relaxed seasonal constraints on ignitions, influencing vegetation composition and erosion. This operated in tandem with climate-driven changes in precipitation to culminate in an ecological transition to an early, pre-agricultural anthropogenic landscape. Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
    • Early Identification of Autism Spectrum Disorder Among Children Aged 4 Years - Early Autism and Developmental Disabilities Monitoring Network, Six Sites, United States, 2016

      Shaw, Kelly A; Maenner, Matthew J; Baio, Jon; Washington, Anita; Christensen, Deborah L; Wiggins, Lisa D; Pettygrove, Sydney; Andrews, Jennifer G; White, Tiffany; Rosenberg, Cordelia Robinson; et al. (CENTERS DISEASE CONTROL & PREVENTION, 2020-03-27)
      Problem/Condition: Autism spectrum disorder (ASD). Period Covered: 2016. Description of System: The Early Autism and Developmental Disabilities Monitoring (Early ADDM) Network, a subset of the overall ADDM Network, is an active surveillance program that estimates ASD prevalence and monitors early identification of ASD among children aged 4 years. Children included in surveillance year 2016 were born in 2012 and had a parent or guardian who lived in the surveillance area in Arizona, Colorado, Missouri, New Jersey, North Carolina, or Wisconsin, at any time during 2016. Children were identified from records of community sources including general pediatric health clinics, special education programs, and early intervention programs. Data from comprehensive evaluations performed by community professionals were abstracted and reviewed by trained clinicians using a standardized ASD surveillance case definition with criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Results: In 2016, the overall ASD prevalence was 15.6 per 1,000 (one in 64) children aged 4 years for Early ADDM Network sites. Prevalence varied from 8.8 per 1,000 in Missouri to 25.3 per 1,000 in New Jersey. At every site, prevalence was higher among boys than among girls, with an overall male-to-female prevalence ratio of 3.5 (95% confidence interval [CI] = 3.1-4.1). Prevalence of ASD between non-Hispanic white (white) and non-Hispanic black (black) children was similar at each site (overall prevalence ratio: 0.9; 95% CI = 0.8-1.1). The prevalence of ASD using DSM-5 criteria was lower than the prevalence using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria at one of four sites that used criteria from both editions. Among sites where 1.60% of children aged 4 years had information about intellectual disability (intelligence quotient <= 70 or examiner's statement of intellectual disability documented in an evaluation), 53% of children with ASD had co-occurring intellectual disability. Of all children aged 4 years with ASD, 84% had a first evaluation at age <= 36 months and 71% of children who met the surveillance case definition had a previous ASD diagnosis from a community provider. Median age at first evaluation and diagnosis for this age group was 26 months and 33 months, respectively. Cumulative incidence of autism diagnoses received by age 48 months was higher for children aged 4 years than for those aged 8 years identified in Early ADDM Network surveillance areas in 2016. Interpretation: In 2016, the overall prevalence ofASD in the Early ADDM Network using DSM-5 criteria (15.6 per 1,000 children aged 4 years) was higher than the 2014 estimate using DSM-5 criteria (14.1 per 1,000). Children born in 2012 had a higher cumulative incidence of ASD diagnoses by age 48 months compared with children born in 2008, which indicates more early identification of ASD in the younger group. The disparity in ASD prevalence has decreased between white and black children. Prevalence of co-occurring intellectual disability was higher than in 2014, suggesting children with intellectual disability continue to be identified at younger ages. More children received evaluations by age 36 months in 2016 than in 2014, which is consistent with Healthy People 2020 goals. Median age at earliest ASD diagnosis has not changed considerably since 2014. Public Health Action: More children aged 4 years with ASD are being evaluated by age 36 months and diagnosed by age 48 months, but there is still room for improvement in early identification. Timely evaluation of children by community providers as soon as developmental concerns have been identified might result in earlier ASD diagnoses, earlier receipt of evidence-based interventions, and improved developmental outcomes.
    • Early Inception of the Laramide Orogeny in Southwestern Montana and Northern Wyoming: Implications for Models of Flat‐Slab Subduction

      Carrapa, B.; DeCelles, P. G.; Romero, M.; Univ Arizona, Dept Geosci (AMER GEOPHYSICAL UNION, 2019-02-16)
      Timing and distribution of magmatism, deformation, exhumation, and basin development have been used to reconstruct the history of Laramide flat-slab subduction under North America during Late Cretaceous-early Cenozoic time. Existing geodynamic models, however, ignore a large (40,000-km(2)) sector of the Laramide foreland in southwestern Montana. The Montana Laramide ranges consist of Archean basement arches (fault-propagation folds) that were elevated by thrust and reverse faults. We present new thermochronological and geochronological data from six Laramide ranges in southwestern Montana (the Beartooth, Gravelly, Ruby and Madison Ranges, and the Tobacco Root and Highland Mountains) that show significant cooling and exhumation during the Early to mid-Cretaceous, much earlier than the record of Laramide exhumation in Wyoming. These data suggest that Laramide-style deformation-driven exhumation slightly predates the eastward sweep of magmatism in western Montana, consistent with geodynamic models involving initial strain propagation into North American cratonic rocks due to stresses associated with a northeastward expanding region of flat-slab subduction. Our results also indicate various degrees of Cenozoic heating and cooling possibly associated with westward rollback of the subducting Farallon slab, followed by Basin-and-Range extension. Plain Language Summary The Laramide region in the western U.S. is characterized by some of the highest topography in North America including the Wind River Range in WY and the Beartooth Range of WY and Montana. These ranges have fed detritus to surrounding basins for millions of years and contributed to modern ecosystems. These high topographic features and basins have significantly impacted paleoenvironmental conditions over geological time. The formation of these high-relief ranges has been linked to deep Earth, geodynamic, processes involving subduction of a flat slab under the North American Plate. Models of flat-slab subduction rely on the timing and pattern of deformation and exhumation of Laramide ranges, which remains poorly understood. Our study provides new data on the timing of deformation and exhumation of Laramide ranges in SW Montana and northern WY capable of testing current models of flat-slab subduction.
    • Early Intervention via Stimulation of the Medial Septal Nucleus Improves Cognition and Alters Markers of Epileptogenesis in Pilocarpine-Induced Epilepsy

      Izadi, A.; Schedlbauer, A.; Ondek, K.; Disse, G.; Ekstrom, A.D.; Cowen, S.L.; Shahlaie, K.; Gurkoff, G.G.; Department of Psychology, University of Arizona; McKnight Brain Institute, University of Arizona (Frontiers Media S.A., 2021)
      Over one-third of patients with temporal lobe epilepsy are refractory to medication. In addition, anti-epileptic drugs often exacerbate cognitive comorbidities. Neuromodulation is an FDA treatment for refractory epilepsy, but patients often wait >20 years for a surgical referral for resection or neuromodulation. Using a rodent model, we test the hypothesis that 2 weeks of theta stimulation of the medial septum acutely following exposure to pilocarpine will alter the course of epileptogenesis resulting in persistent behavioral improvements. Electrodes were implanted in the medial septum, dorsal and ventral hippocampus, and the pre-frontal cortex of pilocarpine-treated rats. Rats received 30 min/day of 7.7 Hz or theta burst frequency on days 4–16 post-pilocarpine, prior to the development of spontaneous seizures. Seizure threshold, spikes, and oscillatory activity, as well as spatial and object-based learning, were assessed in the weeks following stimulation. Non-stimulated pilocarpine animals exhibited significantly decreased seizure threshold, increased spikes, and cognitive impairments as compared to vehicle controls. Furthermore, decreased ventral hippocampal power (6–10 Hz) correlated with both the development of spikes and impaired cognition. Measures of spikes, seizure threshold, and cognitive performance in both acute 7.7 Hz and theta burst stimulated animals were statistically similar to vehicle controls when tested during the chronic phase of epilepsy, weeks after stimulation was terminated. These data indicate that modulation of the septohippocampal circuit early after pilocarpine treatment alters the progression of epileptic activity, resulting in elevated seizure thresholds, fewer spikes, and improved cognitive outcome. Results from this study support that septal theta stimulation has the potential to serve in combination or as an alternative to high frequency thalamic stimulation in refractory cases and that further research into early intervention is critical. © Copyright © 2021 Izadi, Schedlbauer, Ondek, Disse, Ekstrom, Cowen, Shahlaie and Gurkoff.
    • Early life history responses and phenotypic shifts in a rare endemic plant responding to climate change

      Winkler, Daniel E; Lin, Michelle Yu-Chan; Delgadillo, José; Chapin, Kenneth J; Huxman, Travis E; Univ Arizona, Ecol & Evolutionary Biol (OXFORD UNIV PRESS, 2019-10-31)
      Changes in species ranges are anticipated with climate change, where in alpine settings, fragmentation and contraction are likely. This is especially true in high altitude biodiversity hotspots, where warmer growing seasons and increased drought events may negatively impact populations by limiting regeneration. Here, we test for high-altitude species responses to the interactive effects of warming and drought in Heterotheca brandegeei, a perennial cushion plant endemic to alpine outcroppings in Sierra de San Pedro Mártir National Park, Baja California, México. We exposed H. brandegeei seedlings to experimental warming and drought conditions to document early life history responses and the species ability to tolerate climate change. Drought negatively influenced seedling growth, with overall reductions in above- and belowground biomass. Warming and drought each led to substantial reductions in leaf development. At the same time, individuals maintained high specific leaf area and carbon investment in leaves across treatments, suggesting that existing phenotypic variation within populations may be high enough to withstand climate change. However, warming and drought interacted to negatively influence leaf-level water-use efficiency (WUE). Seedling mortality rates were nearly three times higher in warming and drought treatments, suggesting bleak prospects for H. brandegeei populations in future climate conditions. Overall, our results suggest H. brandegeei populations may experience substantial declines under future warmer and drier conditions. Some individuals may be able to establish, albeit, as smaller, more stressed plants. These results further suggest that warming alone may not be as consequential to populations as drought will be in this already water-limited system.
    • Early life metal exposure dysregulates cellular bioenergetics in children with regressive autism spectrum disorder

      Frye, Richard E.; Cakir, Janet; Rose, Shannon; Delhey, Leanna; Bennuri, Sirish C.; Tippett, Marie; Palmer, Raymond F.; Austin, Christine; Curtin, Paul; Arora, Manish; et al. (NATURE PUBLISHING GROUP, 2020-07)
      Neurodevelopmental regression (NDR) is a subtype of autism spectrum disorder (ASD) that manifests as loss of previously acquired developmental milestones. Early life dysregulation of nutritional metals and/or exposure to toxic metals have been associated with ASD, but the underlying biological mechanisms by which metals influence neurodevelopment remain unclear. We hypothesize that metals influences neurodevelopment through dysregulation of bioenergetics. Prenatal and early postnatal metal exposures were measured using validated tooth-matrix biomarkers in 27 ASD cases (13 with NDR) and 7 typically-developing (TD) controls. Mitochondrial respiration and glycolysis were measured in peripheral blood mononuclear cells using the Seahorse XF96. Children with ASD demonstrated lower prenatal and postnatal Copper (Cu) and prenatal Nickel concentrations and Copper-to-Zinc (Cu/Zn) ratio as compared with TD children. Children with ASD and NDR showed greater metal-related disruption of cellular bioenergetics than children with ASD without NDR. For children with ASD and NDR mitochondrial respiration decreased as prenatal Manganese concentration increased and increased as prenatal Zinc concentration increased; glycolysis decreased with increased exposure to prenatal Manganese and Lead and postnatal Manganese. For children with ASD without a history of NDR, glycolysis increased with increased postnatal exposure to Tin. Language and communication scores in children with ASD were positively related to prenatal Cu exposure and Cu/Zn ratio. This study suggests that prenatal nutritional metals may be important for neurodevelopment in children with ASD, and that exposure to toxic metals and differences in nutritional metal exposures is associated with dysregulation of cellular bioenergetics, particularly in the NDR subtype of ASD.
    • Early life risk factors for chronic sinusitis: A longitudinal birth cohort study

      Chang, Eugene H.; Stern, Debra A.; Willis, Amanda L.; Guerra, Stefano; Wright, Anne L.; Martinez, Fernando D.; Univ Arizona, Dept Otolaryngol; Univ Arizona, Asthma & Airway Dis Res Ctr (MOSBY-ELSEVIER, 2018-04)
      Background: Chronic sinusitis is a commonly diagnosed condition in adults who frequently present with late-stage disease and irreversible changes to the sinus mucosa. Understanding the natural history of chronic sinusitis is critical in developing therapies designed to prevent or slow the progression of disease. Objective: We sought to determine early life risk factors for adult sinusitis in a longitudinal cohort study (Tucson Children's Respiratory Study). Methods: Physician-diagnosed sinusitis was reported at age 6. Adult sinusitis between 22 and 32 years was defined as self-reported sinusitis plus physician-ordered sinus radiologic films. Atopy was assessed by skin prick test. Individuals were grouped into 4 phenotypes: no sinusitis (n = 621), transient childhood sinusitis only (n = 57), late-onset adult sinusitis only (n = 68), and early onset chronic sinusitis (childhood and adult sinusitis, n = 26). Results: Sinusitis was present in 10.8% of children and 12.2% of adults. Childhood sinusitis was the strongest independent risk factor for adult sinusitis (odds ratio = 4.2; 95% CI: 2.5-7.1; P < .0001; n = 772). Early onset chronic sinusitis was associated with increased serum IgE levels as early as at 9 months of age, atopy (assessed by skin prick test reactivity), childhood eczema and allergic rhinitis, frequent childhood colds, maternal asthma, and with increased prevalence of concurrent asthma. No association was found between late-onset adult sinusitis and any of the early life risk factors studied. Conclusions: We identified an early onset chronic sinusitis phenotype associated with a predisposition to viral infections/colds in early life, allergies, and asthma. Elucidation of the molecular mechanisms for this phenotype may lead to future therapies to prevent the progression of the disease into adult sinusitis.
    • Early Linguistic Markers of Trauma-Specific Processing Predict Post-trauma Adjustment

      Kleim, Birgit; Horn, Andrea B; Kraehenmann, Rainer; Mehl, Matthias R; Ehlers, Anke; Univ Arizona, Dept Psychol (FRONTIERS MEDIA SA, 2018-12-05)
      Identifying early predictors for psychiatric disorders, such as post-traumatic stress disorder (PTSD), is crucial for effective treatment and prevention efforts. Obtaining such predictors is challenging and methodologically limited, for example by individuals' distress, arousal, and reduced introspective ability. We investigated the predictive power of language-based, implicit markers of psychological processes (N = 163) derived from computerized text-analysis of trauma and control narratives provided within 18 days post-trauma. Trauma narratives with fewer cognitive processing words (indicating less cognitive elaboration), more death-related words (indicating perceived threat to life), and more first-person singular pronouns (indicating self-immersed processing) predicted greater PTSD symptoms at 6 months. These effects were specific to trauma narratives and held after controlling for early PTSD symptom severity and verbal intelligence. When self-report questionnaires of related processes were considered together with the trauma narrative linguistic predictors, use of more first-person singular pronouns remained a significant predictor alongside self-reported mental defeat. Language-based processing markers may complement questionnaire measures in early forecasting of post-trauma adjustment.
    • Early Marine Isotope Stage 3 human occupation of the Shandong Peninsula, coastal North China

      Li, Feng; Wang, Jian; Zhou, Xinying; Wang, Xiaomin; Long, Hao; Chen, Yupeng; Olsen, John W.; Chen, Fuyou; Univ Arizona, Sch Anthropol (WILEY, 2018-11)
      Archeological studies of coastal sites have yielded a large body of information regarding the dispersal of modern humans from Africa and the coastal adaptations of various hominin groups. Coastal areas have been attractive to humans since at least the late Middle Pleistocene, according to research conducted in Africa and the circum-Mediterranean region. However, little information concerning Paleolithic occupations has come to light in coastal areas of China. Here, we report on the chronology, archeology and paleoenvironmental reconstruction of the Pleistocene Dazhushan site on the east coast of the Shandong Peninsula in North China. Evidence indicates that prehistoric humans employing a flake technology occupied the current coastal area of the peninsula by at least early Marine Isotope Stage 3 (MIS 3; c. 57-29 ka) when the region was an inland area dominated by a mixed broadleaved forest and grassland environment occupied by terrestrial herbivores. Based on archeological evidence brought to light along the current Chinese coastline, correlated with sea level changes that have occurred since MIS 3, we suggest that future studies of coastal migrations and adaptations in eastern China will be considerably enhanced by a deeper understanding of the geomorphological evolution of those coastal regions.