Cigarette Smoke Initiates Oxidative Stress-Induced Cellular Phenotypic Modulation Leading to Cerebral Aneurysm Pathogenesis.

OBJECTIVE: Cigarette smoke exposure (CSE) is a risk factor for cerebral aneurysm (CA) formation, but the molecular mechanisms are unclear. Although CSE is known to contribute to excess reactive oxygen species generation, the role of oxidative stress on vascular smooth muscle cell (VSMC) phenotypic modulation and pathogenesis of CAs is unknown. The goal of this study was to investigate whether CSE activates a NOX (NADPH oxidase)-dependent pathway leading to VSMC phenotypic modulation and CA formation and rupture. APPROACH AND RESULTS: In cultured cerebral VSMCs, CSE increased expression of NOX1 and reactive oxygen species which preceded upregulation of proinflammatory/matrix remodeling genes (MCP-1, MMPs [matrix metalloproteinase], TNF-α, IL-1β, NF-κB, KLF4 [Kruppel-like factor 4]) and downregulation of contractile genes (SM-α-actin [smooth muscle α actin], SM-22α [smooth muscle 22α], SM-MHC [smooth muscle myosin heavy chain]) and myocardin. Inhibition of reactive oxygen species production and knockdown of NOX1 with siRNA or antisense decreased CSE-induced upregulation of NOX1 and inflammatory genes and downregulation of VSMC contractile genes and myocardin. p47phox-/- NOX knockout mice, or pretreatment with the NOX inhibitor, apocynin, significantly decreased CA formation and rupture compared with controls. NOX1 protein and mRNA expression were similar in p47phox-/- mice and those pretreated with apocynin but were elevated in unruptured and ruptured CAs. CSE increased CA formation and rupture, which was diminished with apocynin pretreatment. Similarly, NOX1 protein and mRNA and reactive oxygen species were elevated by CSE, and in unruptured and ruptured CAs. CONCLUSIONS: CSE initiates oxidative stress-induced phenotypic modulation of VSMCs and CA formation and rupture. These molecular changes implicate oxidative stress in the pathogenesis of CAs and may provide a potential target for future therapeutic strategies

Ecological and Genomic Attributes of Novel Bacterial Taxa That Thrive in Subsurface Soil Horizons.

While most bacterial and archaeal taxa living in surface soils remain undescribed, this problem is exacerbated in deeper soils, owing to the unique oligotrophic conditions found in the subsurface. Additionally, previous studies of soil microbiomes have focused almost exclusively on surface soils, even though the microbes living in deeper soils also play critical roles in a wide range of biogeochemical processes. We examined soils collected from 20 distinct profiles across the United States to characterize the bacterial and archaeal communities that live in subsurface soils and to determine whether there are consistent changes in soil microbial communities with depth across a wide range of soil and environmental conditions. We found that bacterial and archaeal diversity generally decreased with depth, as did the degree of similarity of microbial communities to those found in surface horizons. We observed five phyla that consistently increased in relative abundance with depth across our soil profiles: Chloroflexi, Nitrospirae, Euryarchaeota, and candidate phyla GAL15 and Dormibacteraeota (formerly AD3). Leveraging the unusually high abundance of Dormibacteraeota at depth, we assembled genomes representative of this candidate phylum and identified traits that are likely to be beneficial in low-nutrient environments, including the synthesis and storage of carbohydrates, the potential to use carbon monoxide (CO) as a supplemental energy source, and the ability to form spores. Together these attributes likely allow members of the candidate phylum Dormibacteraeota to flourish in deeper soils and provide insight into the survival and growth strategies employed by the microbes that thrive in oligotrophic soil environments.IMPORTANCE Soil profiles are rarely homogeneous. Resource availability and microbial abundances typically decrease with soil depth, but microbes found in deeper horizons are still important components of terrestrial ecosystems. By studying 20 soil profiles across the United States, we documented consistent changes in soil bacterial and archaeal communities with depth. Deeper soils harbored communities distinct from those of the more commonly studied surface horizons. Most notably, we found that the candidate phylum Dormibacteraeota (formerly AD3) was often dominant in subsurface soils, and we used genomes from uncultivated members of this group to identify why these taxa are able to thrive in such resource-limited environments. Simply digging deeper into soil can reveal a surprising number of novel microbes with unique adaptations to oligotrophic subsurface conditions

Financing Direct Democracy: Revisiting the Research on Campaign Spending and Citizen Initiatives

The conventional view in the direct democracy literature is that spending against a measure is more effective than spending in favor of a measure, but the empirical results underlying this conclusion have been questioned by recent research. We argue that the conventional finding is driven by the endogenous nature of campaign spending: initiative proponents spend more when their ballot measure is likely to fail. We address this endogeneity by using an instrumental variables approach to analyze a comprehensive dataset of ballot propositions in California from 1976 to 2004. We find that both support and opposition spending on citizen initiatives have strong, statistically significant, and countervailing effects. We confirm this finding by looking at time series data from early polling on a subset of these measures. Both analyses show that spending in favor of citizen initiatives substantially increases their chances of passage, just as opposition spending decreases this likelihood

Visual function, traumatic brain injury, and posttraumatic stress disorder

Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are signature injuries of the Iraq and Afghanistan conflicts. The conditions can be comorbid and have overlapping signs and symptoms, making it difficult to diagnose and treat each. TBI is associated with numerous changes in vision function, but vision problems secondary to PTSD have not been documented. To address this shortcoming, we reviewed the medical records of 100 patients with a history of TBI, noting PTSD diagnoses, visual symptoms, vision function abnormalities, and medications with visual side effects. Forty-one patients had PTSD and 59 did not. High rates of binocular vision and oculomotor function deficits were measured in patients with a history of TBI, but no significant differences between patients with or without PTSD were evident. However, compared to patients without PTSD, patients with PTSD had more self-reported visual symptoms in all four assessments and the complaint rates were significantly higher for light sensitivity and reading problems. Together, these findings may be beneficial in understanding vision problems in patients with TBI and PTSD as comorbid conditions compared with those with TBI alone

The Vehicle, Spring 1974

Table of Contents PhotoJim Painterpage 1 Six Poems of the LandRay Schmuddepage 5 At Last to Find FreedomJann Briesacherpage 7 The Last IrisMarjorie Thoelepage 9 (Untitled)Melinda E. Recordpage 10 MenJan Schroederpage 10 ImpressionsJudy Bardpage 11 ScaredAnita Surpage 11 Loved and LostJan Schroederpage 12 Dripped-Over WaxAnita Surpage 13 The Crowded RoomWilliam E. Uteschpage 14 A River in IllinoisJames Jonespage 14 Sneeze SeasonDarlene A. Moorepage 14 ChangesMark Chianakaspage 15 PhotoJim Painterpage 16 Wedding VowsJann Briesacherpage 17 PhotoJim Painterpage 18 PhotoJim Painterpage 19 PhotoJim Painterpage 20 PhotoJim Painterpage 21 PhotoJim Painterpage 22 PhotoLarry Smyserpage 23 From Outside ColoradoRay Schmuddepage 24 Dairy QueenGayle Gleichmanpage 26 With Sunstreaks in our HairNancy Broom Brownpage 33 PhotoJim Painterpage 34 Water\u27s EdgeMarjorie Thoelepage 35 My 665th Illusion of SanityGordon Glessnerpage 36 Is it my turn to do the laundry again??? Jann Briesacherpage 38 TV Teachingbobbdoddpage 39 GuidanceWendy Diane Wielandpage 40 PhotoJim Painterpage 41 RaindropsJane Ann Beerspage 42 WaitingJan Schroederpage 42 To JonJudy Bardpage 43 One Autumn Day in 1971E. Christmanpage 43 More Surely Than Picture AlbumsMarjorie Thoelepage 44 WingspanningNancy Broom Brownpage 45 ReligionMelinda E. Recordpage 45 Rosalie StevensonMark Holleypage 46 PhotoJim Painterpage 47 WhiteShirley A. Rardinpage 48 The Beginning of a Perfect DayShirley A. Rardinpage 49 PhotoMichael Chenpage 50 Rosethorn Wall of June 17bobbdoddpage 51 ManJan Schroederpage 51 HaikuJudy Bardpage 51 You know it leaves me emptyJames Osbornepage 52 For JesseJames Osbornepage 52 EndingsMark Chianakaspage 53 ConfusionGary L. Owenspage 53 PhotoMichael Chenpage 54 PoemsJann Briesacherpage 54 Journey of just oneNancy Broom Brownpage 55 Blackbirds in IllinoisJames Jonespage 56 PoemsJann Briesacherpage 56 PhotoMichael Chenpage 57 I am a poemDarlene A. Moorepage 57 A Glimpse of ParadiseJann Briesacherpage 57 PhotoJim Painterpage 58 PoemSheila Marie Foorpage 59 In my windowBarbara S. Meyerpage 59 Section 4., Draft 3bobbdoddpage 60 PhotoJim Painterpage 61 PoemJann Briesacherpage 61 PhotoGary Deanpage 62 I amWilliam E. Uteschpage 62 To a tank-car in IllinoisJames Jonespage 63 PoemJane Ann Beerspage 63 PoemsJann Briesacherpage 63 Editor\u27s Pagepage 64https://thekeep.eiu.edu/vehicle/1031/thumbnail.jp

Solar Wind Turbulence and the Role of Ion Instabilities

International audienc

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

The Vehicle, Spring 1974

Table of Contents PhotoJim Painterpage 1 Six Poems of the LandRay Schmuddepage 5 At Last to Find FreedomJann Briesacherpage 7 The Last IrisMarjorie Thoelepage 9 (Untitled)Melinda E. Recordpage 10 MenJan Schroederpage 10 ImpressionsJudy Bardpage 11 ScaredAnita Surpage 11 Loved and LostJan Schroederpage 12 Dripped-Over WaxAnita Surpage 13 The Crowded RoomWilliam E. Uteschpage 14 A River in IllinoisJames Jonespage 14 Sneeze SeasonDarlene A. Moorepage 14 ChangesMark Chianakaspage 15 PhotoJim Painterpage 16 Wedding VowsJann Briesacherpage 17 PhotoJim Painterpage 18 PhotoJim Painterpage 19 PhotoJim Painterpage 20 PhotoJim Painterpage 21 PhotoJim Painterpage 22 PhotoLarry Smyserpage 23 From Outside ColoradoRay Schmuddepage 24 Dairy QueenGayle Gleichmanpage 26 With Sunstreaks in our HairNancy Broom Brownpage 33 PhotoJim Painterpage 34 Water\u27s EdgeMarjorie Thoelepage 35 My 665th Illusion of SanityGordon Glessnerpage 36 Is it my turn to do the laundry again??? Jann Briesacherpage 38 TV Teachingbobbdoddpage 39 GuidanceWendy Diane Wielandpage 40 PhotoJim Painterpage 41 RaindropsJane Ann Beerspage 42 WaitingJan Schroederpage 42 To JonJudy Bardpage 43 One Autumn Day in 1971E. Christmanpage 43 More Surely Than Picture AlbumsMarjorie Thoelepage 44 WingspanningNancy Broom Brownpage 45 ReligionMelinda E. Recordpage 45 Rosalie StevensonMark Holleypage 46 PhotoJim Painterpage 47 WhiteShirley A. Rardinpage 48 The Beginning of a Perfect DayShirley A. Rardinpage 49 PhotoMichael Chenpage 50 Rosethorn Wall of June 17bobbdoddpage 51 ManJan Schroederpage 51 HaikuJudy Bardpage 51 You know it leaves me emptyJames Osbornepage 52 For JesseJames Osbornepage 52 EndingsMark Chianakaspage 53 ConfusionGary L. Owenspage 53 PhotoMichael Chenpage 54 PoemsJann Briesacherpage 54 Journey of just oneNancy Broom Brownpage 55 Blackbirds in IllinoisJames Jonespage 56 PoemsJann Briesacherpage 56 PhotoMichael Chenpage 57 I am a poemDarlene A. Moorepage 57 A Glimpse of ParadiseJann Briesacherpage 57 PhotoJim Painterpage 58 PoemSheila Marie Foorpage 59 In my windowBarbara S. Meyerpage 59 Section 4., Draft 3bobbdoddpage 60 PhotoJim Painterpage 61 PoemJann Briesacherpage 61 PhotoGary Deanpage 62 I amWilliam E. Uteschpage 62 To a tank-car in IllinoisJames Jonespage 63 PoemJane Ann Beerspage 63 PoemsJann Briesacherpage 63 Editor\u27s Pagepage 64https://thekeep.eiu.edu/vehicle/1031/thumbnail.jp

The Actin Associated Protein Palladin Is Important for the Early Smooth Muscle Cell Differentiation

Palladin, an actin associated protein, plays a significant role in regulating cell adhesion and cell motility. Palladin is important for development, as knockdown in mice is embryonic lethal, yet its role in the development of the vasculature is unknown. We have shown that palladin is essential for the expression of smooth muscle cells (SMC) marker genes and force development in response to agonist stimulation in palladin deficient SMCs. The goal of the study was to determine the molecular mechanisms underlying palladin's ability to regulate the expression of SMC marker genes. Results showed that palladin expression was rapidly induced in an A404 cell line upon retinoic acid (RA) induced differentiation. Suppression of palladin expression with siRNAs inhibited the expression of RA induced SMC differentiation genes, SM α-actin (SMA) and SM22, whereas over-expression of palladin induced SMC gene expression. Chromatin immunoprecipitation assays provided evidence that palladin bound to SMC genes, whereas co-immunoprecipitation assays also showed binding of palladin to myocardin related transcription factors (MRTFs). Endogenous palladin was imaged in the nucleus, increased with leptomycin treatment and the carboxyl-termini of palladin co-localized with MRTFs in the nucleus. Results support a model wherein palladin contributes to SMC differentiation through regulation of CArG-SRF-MRTF dependent transcription of SMC marker genes and as previously published, also through actin dynamics. Finally, in E11.5 palladin null mouse embryos, the expression of SMA and SM22 mRNA and protein is decreased in the vessel wall. Taken together, our findings suggest that palladin plays a key role in the differentiation of SMCs in the developing vasculature

Assessing the quality of models of the ambient solar wind

In this paper we present an assessment of the status of models of the global Solar Wind in the inner heliosphere. We limit our discussion to the class of models designed to provide solar wind forecasts, excluding those designed for the purpose of testing physical processes in idealized configurations. In addition, we limit our discussion to modeling of the ‘ambient’ wind in the absence of coronal mass ejections. In this assessment we cover use of the models both in forecast mode and as tools for scientific research. We present a brief history of the development of these models, discussing the range of physical approximations in use. We discuss the limitations of the data inputs available to these models and its impact on their quality. We also discuss current model development trends