Exposure to erionite, an asbestos-like mineral, causes unprecedented rates of malignant mesothelioma (MM) mortality in some Turkish villages. Erionite deposits are present in at least 12 US states. ...We investigated whether increased urban development has led to erionite exposure in the United States and after preliminary exploration, focused our studies on Dunn County, North Dakota (ND). In Dunn County, ND, we discovered that over the past three decades, more than 300 miles of roads were surfaced with erionite-containing gravel. To determine potential health implications, we compared erionite from the Turkish villages to that from ND. Our study evaluated airborne point exposure concentrations, examined the physical and chemical properties of erionite, and examined the hallmarks of mesothelial cell transformation in vitro and in vivo. Airborne erionite concentrations measured in ND along roadsides, indoors, and inside vehicles, including school buses, equaled or exceeded concentrations in Boyali, where 6.25% of all deaths are caused by MM. With the exception of outdoor samples along roadsides, ND concentrations were lower than those measured in Turkish villages with MM mortality ranging from 20 to 50%. The physical and chemical properties of erionite from Turkey and ND are very similar and they showed identical biological activities. Considering the known 30- to 60-y latency for MM development, there is reason for concern for increased risk in ND in the future. Our findings indicate that implementation of novel preventive and early detection programs in ND and other erionite-rich areas of the United States, similar to efforts currently being undertaken in Turkey, is warranted.
Heme oxygenase-1 (HO-1) is an inducible stress-response protein that imparts antioxidant and antiapoptotic effects. However, its pathophysiological role in cardiac remodeling and chronic heart ...failure (HF) is unknown. We hypothesized that induction of HO-1 in HF alleviates pathological remodeling.
Adult male nontransgenic and myocyte-restricted HO-1 transgenic mice underwent either sham operation or coronary ligation to induce HF. Four weeks after ligation, nontransgenic HF mice exhibited postinfarction left ventricular (LV) remodeling and dysfunction, hypertrophy, fibrosis, oxidative stress, apoptosis, and reduced capillary density, associated with a 2-fold increase in HO-1 expression in noninfarcted myocardium. Compared with nontransgenic mice, HO-1 transgenic HF mice exhibited significantly (P<0.05) improved postinfarction survival (94% versus 57%) and less LV dilatation (end-diastolic volume, 46+/-8 versus 85+/-32 microL), mechanical dysfunction (ejection fraction, 65+/-9% versus 49+/-16%), hypertrophy (LV/tibia length 4.4+/-0.4 versus 5.2+/-0.6 mg/mm), interstitial fibrosis (11.2+/-3.1% versus 18.5+/-3.5%), and oxidative stress (3-fold reduction in tissue malondialdehyde). Moreover, myocyte-specific HO-1 overexpression in HF promoted tissue neovascularization and ameliorated myocardial p53 expression (2-fold reduction) and apoptosis. In isolated mitochondria, mitochondrial permeability transition was inhibited by HO-1 in a carbon monoxide (CO)-dependent manner and was recapitulated by the CO donor tricarbonylchloro(glycinato)ruthenium(II) (CORM-3). HO-1-derived CO also prevented H2O2-induced cardiomyocyte apoptosis and cell death. Finally, in vivo treatment with CORM-3 alleviated postinfarction LV remodeling, p53 expression, and apoptosis.
HO-1 induction in the failing heart is an important cardioprotective adaptation that opposes pathological LV remodeling, and this effect is mediated, at least in part, by CO-dependent inhibition of mitochondrial permeability transition and apoptosis. Augmentation of HO-1 or its product, CO, may represent a novel therapeutic strategy for ameliorating HF.
Ingested soil and surface dust may be important contributors to elevated blood lead (Pb) levels in children exposed to Pb contaminated environments. Mitigation strategies have typically focused on ...excavation and removal of the contaminated soil. However, this is not always feasible for addressing widely disseminated contamination in populated areas often encountered in urban environments. The rationale for amending soils with phosphate is that phosphate will promote formation of highly insoluble Pb species (e.g., pyromorphite minerals) in soil, which will remain insoluble after ingestion and, therefore, inaccessible to absorption mechanisms in the gastrointestinal tract (GIT). Amending soil with phosphate might potentially be used in combination with other methods that reduce contact with or migration of contaminated soils, such as covering the soil with a green cap such as sod, clean soil with mulch, raised garden beds, or gravel. These remediation strategies may be less expensive and far less disruptive than excavation and removal of soil. This review evaluates evidence for efficacy of phosphate amendments for decreasing soil Pb bioavailability. Evidence is reviewed for (1) physical and chemical interactions of Pb and phosphate that would be expected to influence bioavailability, (2) effects of phosphate amendments on soil Pb bioaccessibility (i.e., predicted solubility of Pb in the GIT), and (3) results of bioavailability bioassays of amended soils conducted in humans and animal models. Practical implementation issues, such as criteria and methods for evaluating efficacy, and potential effects of phosphate on mobility and bioavailability of co-contaminants in soil are also discussed.
We report Northern Extended Millimeter Array CO(J = 3 − 2) observations of the dusty star-forming galaxy ACT-S J020941+001557 at z = 2.5528, which was detected as an unresolved source in the Atacama ...Cosmology Telescope (ACT) equatorial survey. Our spatially resolved spectral line data support the derivation of a gravitational lens model from 37 independent velocity channel maps using a pixel-based algorithm, from which we infer a velocity-dependent magnification factor 7-22 with a luminosity-weighted mean . The resulting source-plane reconstruction is consistent with a rotating disk, although other scenarios cannot be ruled out by our data. After correction for lensing, we derive a line luminosity , a cold gas mass , a dynamical mass , and a gas mass fraction . The line brightness temperature ratio of r3,1 1.6 relative to a Green Bank Telescope CO(J = 1 − 0) detection may be elevated by a combination of external heating of molecular clouds, differential lensing, and/or pointing errors.
Injury to the cellular components of the vascular wall and blood by endogenous and exogenous chemicals has been associated with atherosclerosis in humans and experimental systems. The genetic and ...molecular mechanisms responsible for initiation and promotion of atherosclerotic changes include modulation of extracellular matrix-integrin axis, genes involved in the regulation of growth and differentiation and possibly, genomic stability. This review summarizes seminal studies over the past 20 years that shed light on critical gene-gene and gene-environment interactions mediating the atherogenic response to chemical injury.
Multiple in vitro model systems are currently available to evaluate structure and function relationships in the cardiovascular system as well as the system’s response to injury. As the level of ...molecular sophistication continues to advance, so does the level of complexity of the analysis. One of the most daunting tasks faced by researchers interested in studying cardiovascular function and injury is the selection of the system or systems best suited to answer the particular question at hand. In order to successfully apply any given model system, the researcher must recognize the advantages and limitations in the system of choice. This review provides a listing of the historical and modern techniques used to study cardiovascular function and chemically-induced toxicity. With the growing number of new pharmaceuticals discovered each year, it is imperative to use experimental model systems that allow for identification of targets that participate in or mediate adverse outcomes. Clearly, in vitro analysis cannot replace in vivo experimentation, but the methods currently available allow for a reduction in the number of animals used for experimentation and a better understanding of the complexity associated with the injury response.
Scientific and medical evidence over the past 30 years has established striking parallels between atherosclerosis and cancer--pathogenetic relationships that cross the boundaries of fiction into the ...realm of reason. Both diseases in humans are characterized by uncontrolled regulation of cellular growth and differentiation and share many common genomic targets during the course of growth dysregulation. Such parallels can be reconciled if atherosclerotic plaques are viewed as neoplasms of smooth muscle origin.
Planck intermediate results Akrami, Y.; Ashdown, M.; Aumont, J. ...
Astronomy and astrophysics (Berlin),
12/2020, Letnik:
644
Journal Article
Recenzirano
Odprti dostop
We describe an extension of the most recent version of the
Planck
Catalogue of Compact Sources (PCCS2), produced using a new multi-band Bayesian Extraction and Estimation Package (
BeeP
).
BeeP
...assumes that the compact sources present in PCCS2 at 857 GHz have a dust-like spectral energy distribution (SED), which leads to emission at both lower and higher frequencies, and adjusts the parameters of the source and its SED to fit the emission observed in
Planck
’s three highest frequency channels at 353, 545, and 857 GHz, as well as the IRIS map at 3000 GHz. In order to reduce confusion regarding diffuse cirrus emission,
BeeP
’s data model includes a description of the background emission surrounding each source, and it adjusts the confidence in the source parameter extraction based on the statistical properties of the spatial distribution of the background emission.
BeeP
produces the following three new sets of parameters for each source: (a) fits to a modified blackbody (MBB) thermal emission model of the source; (b) SED-independent source flux densities at each frequency considered; and (c) fits to an MBB model of the background in which the source is embedded.
BeeP
also calculates, for each source, a reliability parameter, which takes into account confusion due to the surrounding cirrus. This parameter can be used to extract sub-samples of high-frequency sources with statistically well-understood properties. We define a high-reliability subset (
BeeP/base
), containing 26 083 sources (54.1% of the total PCCS2 catalogue), the majority of which have no information on reliability in the PCCS2. We describe the characteristics of this specific high-quality subset of PCCS2 and its validation against other data sets, specifically for: the sub-sample of PCCS2 located in low-cirrus areas; the
Planck
Catalogue of Galactic Cold Clumps; the
Herschel
GAMA15-field catalogue; and the temperature- and spectral-index-reconstructed dust maps obtained with
Planck
’s Generalized Needlet Internal Linear Combination method. The results of the
BeeP
extension of PCCS2, which are made publicly available via the
Planck
Legacy Archive, will enable the study of the thermal properties of well-defined samples of compact Galactic and extragalactic dusty sources.
Altered degradation of extracellular matrix (ECM) underlies vascular remodeling, a hallmark in the pathogenesis of cardiovascular diseases including hypertension and aneurysmal dilatation. Although ...alcohol is recognized as a risk factor for certain cardiovascular disease states, its role in vascular remodeling has not been completely explored. We studied the effect of chronic alcohol consumption on upregulation of the enzymatic activity of matrix metalloproteinase-2 (MMP-2) as a possible pathway for large vessel remodeling. For this purpose, female rats were placed on one of three diets: a modified Lieber-DeCarli liquid diet containing 35% ethanol-derived calories, a pair-fed liquid diet with ethanol replaced by isocaloric maltose-dextrin, or a standard rat pellet. Weekly blood alcohol concentration averaged 117 ± 7.9 mg/dl for the alcohol-fed rats. At 2, 4, and 72 weeks, aortas were removed and processed for measuring MMPs activity by gelatin zymography. Aortic extracts from rats on long-term (72 weeks), but not the short-term (2 and 4 weeks), alcohol diets showed increased MMP-2 activity. Furthermore, histochemical analysis of the aortas showed distinct disruption of the elastic fibers only in the 72 weeks alcohol-fed rats, compared to the control animals. These observations demonstrate that long-term alcohol consumption up-regulates MMP-2 activity, which is coincident with the alteration of aortic ECM composition through the degradation of vascular elastin components.
Responding to a model of juvenile offender case supervision that called for a new intervention paradigm to guide the work of probation and parole officers, the present article reports on the use of a ...family-based parole initiative known as the Growing Up FAST program. Developed in part as a tool for use within this new intervention paradigm, the Growing Up FAST parole program targets serious youthful offenders who have been released from juvenile correctional facilities and their families. Based on elements contained within the “what works” literature and the Balanced and Restorative Justice model, this program recognizes the central role that field staff can play in rehabilitation efforts. Demographic information and formative data regarding the first set of families to participate in this program are presented, then program limitations and lessons learned as part of the initial offering of this parole initiative are discussed.
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