Metallic nickel nano- and fine particles induce JB6 cell apoptosis through a caspase-8/AIF mediated cytochrome c-independent pathway

<p>Abstract</p> <p>Background</p> <p>Carcinogenicity of nickel compounds has been well documented. However, the carcinogenic effect of metallic nickel is still unclear. The present study investigates metallic nickel nano- and fine particle-induced apoptosis and the signal pathways involved in this process in JB6 cells. The data obtained from this study will be of benefit for elucidating the pathological and carcinogenic potential of metallic nickel particles.</p> <p>Results</p> <p>Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we found that metallic nickel nanoparticles exhibited higher cytotoxicity than fine particles. Both metallic nickel nano- and fine particles induced JB6 cell apoptosis. Metallic nickel nanoparticles produced higher apoptotic induction than fine particles. Western-blot analysis showed an activation of proapoptotic factors including Fas (CD95), Fas-associated protein with death domain (FADD), caspase-8, death receptor 3 (DR3) and BID in apoptotic cells induced by metallic nickel particles. Immunoprecipitation (IP) western blot analysis demonstrated the formation of the Fas-related death-inducing signaling complex (DISC) in the apoptotic process. Furthermore, lamin A and beta-actin were cleaved. Moreover, we found that apoptosis-inducing factor (AIF) was up-regulated and released from mitochondria to cytoplasm. Interestingly, although an up-regulation of cytochrome <it>c </it>was detected in the mitochondria of metallic nickel particle-treated cells, no cytochrome <it>c </it>release from mitochondria to cytoplasm was found. In addition, activation of antiapoptotic factors including phospho-Akt (protein kinase B) and Bcl-2 was detected. Further studies demonstrated that metallic nickel particles caused no significant changes in the mitochondrial membrane permeability after 24 h treatment.</p> <p>Conclusion</p> <p>In this study, metallic nickel nanoparticles caused higher cytotoxicity and apoptotic induction than fine particles in JB6 cells. Apoptotic cell death induced by metallic nickel particles in JB6 cells is through a caspase-8/AIF mediated cytochrome <it>c</it>-independent pathway. Lamin A and beta-actin are involved in the process of apoptosis. Activation of Akt and Bcl-2 may play an important role in preventing cytochrome <it>c </it>release from mitochondria to the cytoplasm and may also be important in the carcinogenicity of metallic nickel particles. In addition, the results may be useful as an important reference when comparing the toxicities of different nickel compounds.</p

Equitable Access to Mental Health and Substance Use Care: An Urgent Need

Due to the deepening mental health and substance use crisis in the U.S., there's an urgent need for equitable access to care that is timely, clinically effective, and adequately reimbursed by insurers. This need encompasses psychiatrists, psychologists, social workers, other counselors, and treatment facilities as well as mental health and substance use care delivered by primary care providers.Multiple studies, including analyses of insurance claims and surveys of employers and providers, have demonstrated that in-network health insurance coverage for treatment of mental health and substance use conditions remains inadequate and not "on par" with access to in-network health insurance coverage for physical health treatment.This patient-experience survey conducted by NORC (Survey) explored key topics such as: 1) how often mental health or substance use care is needed but not received; 2) how difficult it is to find in-network providers accepting new patients; 3) how often and why patients use out-ofnetwork providers for mental health or substance use care versus physical health care; 4) how often patients feel that mental health or substance use care from PCPs and other physical health providers is insufficient; 5) how often services are denied; and more

Loss of H2A.Z Is Not Sufficient to Determine Transcriptional Activity of Snf2-Related CBP Activator Protein or p400 Complexes

The p400 and SRCAP (Snf2-related CBP activator protein) complexes remodel chromatin by catalyzing deposition of histone H2A.Z into nucleosomes. This remodeling activity has been proposed as a basis for regulation of transcription by these complexes. Transcript levels of p21 or Sp1 mRNAs after knockdown of p400 or SRCAP reveals that each regulates transcription of these promoters differently. In this study, we asked whether deposition of H2A.Z within specific nucleosomes by p400 or SRCAP dictates transcriptional activity. Our data indicates that nucleosome density at specific p21 or Sp1 promoter positions is not altered by the loss of either remodeling complex. However, knockdown of SRCAP or p400 reduces deposition of H2A.Z∼50% into all p21 and Sp1 promoter nucleosomes. Thus, H2A.Z deposition is not targeted to specific nucleosomes. These results indicate that the deposition of H2A.Z by the p400 or SRCAP complexes is not sufficient to determine how each regulates transcription. This conclusion is further supported by studies that demonstrate a SRCAPΔATP mutant unable to deposit H2A.Z has similar transcriptional activity as wild-type SRCAP

Error Patterns in Apraxia of Speech

TB

Cyanidin-3-Glucoside, A Natural Product Derived From Blackberry, Exhibits Chemopreventive And Chemotherapeutic Activity

Epidemiological data suggest that consumption of fruits and vegetables has been associated with a lower incidence of cancer. Cyanidin-3-glucoside (C3G), a compound found in blackberry and other food products, was shown to possess chemopreventive and chemotherapeutic activity in the present study. In cultured JB6 cells, C3G was able to scavenge ultraviolet B-induced *OH and O2-* radicals. In vivo studies indicated that C3G treatment decreased the number of non-malignant and malignant skin tumors per mouse induced by 12-O-tetradecanolyphorbol-13-acetate (TPA) in 7,12-dimethylbenz[a]anthracene-initiated mouse skin. Pretreatment of JB6 cells with C3G inhibited UVB- and TPA-induced transactivation of NF-kappaB and AP-1 and expression of cyclooxygenase-2 and tumor necrosis factor-alpha. These inhibitory effects appear to be mediated through the inhibition of MAPK activity. C3G also blocked TPA-induced neoplastic transformation in JB6 cells. In addition, C3G inhibited proliferation of a human lung carcinoma cell line, A549. Animal studies showed that C3G reduced the size of A549 tumor xenograft growth and significantly inhibited metastasis in nude mice. Mechanistic studies indicated that C3G inhibited migration and invasion of A549 tumor cells. These finding demonstrate for the first time that a purified compound of anthocyanin inhibits tumor promoter-induced carcinogenesis and tumor metastasis in vivo

A continental analysis of ecosystem vulnerability to atmospheric nitrogen deposition

Atmospheric nitrogen (N) deposition has been shown to decrease plant species richness along regional deposition gradients in Europe and in experimental manipulations. However, the general response of species richness to N deposition across different vegetation types, soil conditions, and climates remains largely unknown even though responses may be contingent on these environmental factors. We assessed the effect of N deposition on herbaceous richness for15,136 forest, woodland, shrubland, and grassland sites across the continental United States, to address how edaphic and climatic conditions altered vulnerability to this stressor. In our dataset, with N deposition ranging from 1 to 19 kg N·ha−1·y−1, we found a unimodal relationship; richness increased at low deposition levels and decreased above 8.7 and 13.4 kg N·ha−1·y−1 in open and closed-canopy vegetation, respectively. N deposition exceeded critical loads for loss of plant species richness in 24% of 15,136 sites examined nationwide. There were negative relationships between species richness and N deposition in 36% of 44 community gradients. Vulnerability to N deposition was consistently higher in more acidic soils whereas the moderating roles of temperature and precipitation varied across scales. We demonstrate here that negative relationships between N deposition and species richness are common, albeit not universal, and that fine-scale processes can moderate vegetation responses to N deposition. Our results highlight the importance of contingent factors when estimating ecosystem vulnerability to N deposition and suggest that N deposition is affecting species richness in forested and nonforested systems across much of the continental United States

The Effect of HIV Infection on the Risk, Frequency, and Intensity of Plasmodium falciparum Parasitemia in Primigravid and Multigravid Women in Malawi

Human immunodeficiency virus (HIV) is common in pregnant women in many malaria-endemic regions and may increase risk of placental parasitemia. Placental malaria is more common in primigravidae than multigravidae, but the relationship between HIV and malaria across gravidities is not well characterized. We recruited pregnant Malawian women during the second trimester and followed them until delivery. Parasitemia was assessed at enrollment, follow-up visits, and delivery, when placental blood was sampled. There was no difference in risk of parasitemia between HIV-positive and HIV-negative primigravidae. Among multigravidae, HIV-infected women had greater than twice the risk of parasitemia as HIV-uninfected women throughout follow-up. Human immunodeficiency virus was also associated with more frequent peripheral parasitemia in multigravidae but not primigravidae. Both HIV and primigravid status were independently associated with higher peripheral and placental parasite densities. Although risk of parasitemia is lower in multigravidae than primigravidae, the HIV effect on risk of malaria is more pronounced in multigravidae

Nurses Alumni Association Bulletin, Fall 1995

1995-1996 Meeting Dates Calendar 1996 Annual Luncheon-Meeting Notice Officers and Committee Chairs Bulletin Publication Committee 1995-1996 Meeting Dates Calendar The President\u27s Message Financial Report What\u27s New Fiftieth Anniversary Resume of Minutes of Alumni Association Meetings Scholarship Funds at Work CAHS Alumni Board/Diploma School Alumni Office News Jefferson Health System Oldest Veteran Dies 1OOth Anniversary Pearl Harbor Remembered Memories Janet Hindson Retires Happy Birthday Scholarship Fund donors for 1994 Committee Reports By-Laws Development Bulletin Relief Fund Satellite Social Scholarship In Memoriam, Names of Deceased Graduates Class News Luncheon Photos Jefferson Alumni Identification Card The Diploma School of Nursing Alumni Association-Mabel C. Prevost Letter of Appreciation Tribute To a Mother An End Must Come Stuff For Senior Citizens to Chuckle Over Membership Application Relief Fund Application To Order: A Chronological History and Alumni Directory From TJU Bookstore Scholarship Fund Application Pins, Transcripts, Class Address List, Change of Address Forms, Alumni Identification Card Campus Map Picture - Class of 1893-189

Synthesis

Human activity in the last century has led to a substantial increase in nitrogen (N) emissions and deposition. This N deposition has reached a level that has caused or is likely to cause alterations to the structure and function of many ecosystems across the United States. One approach for quantifying the level of pollution that would be harmful to ecosystems is the critical loads approach. The critical load is dei ned as the level of a pollutant below which no detrimental ecological effect occurs over the long term according to present knowledge. The objective of this project was to synthesize current research relating atmospheric N deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The receptors that we evaluated included freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical, and (2) individual species, population, and community responses. This report synthesizes current research relating atmospheric nitrogen (N) deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The report evaluates the following receptors: freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical; and (2) individual species, population, and community responses. The range of critical loads for nutrient N reported for U.S. ecoregions, inland surface waters, and freshwater wetlands is 1 to 39 kg N ha-1 y-1. This range spans the range of N deposition observed over most of the country. The empirical critical loads for N tend to increase in the following sequence for different life forms: diatoms, lichens and bryophytes, mycorrhizal fungi, herbaceous plants and shrubs, trees

Synthesis

Human activity in the last century has led to a substantial increase in nitrogen (N) emissions and deposition. This N deposition has reached a level that has caused or is likely to cause alterations to the structure and function of many ecosystems across the United States. One approach for quantifying the level of pollution that would be harmful to ecosystems is the critical loads approach. The critical load is dei ned as the level of a pollutant below which no detrimental ecological effect occurs over the long term according to present knowledge. The objective of this project was to synthesize current research relating atmospheric N deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The receptors that we evaluated included freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical, and (2) individual species, population, and community responses. This report synthesizes current research relating atmospheric nitrogen (N) deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The report evaluates the following receptors: freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical; and (2) individual species, population, and community responses. The range of critical loads for nutrient N reported for U.S. ecoregions, inland surface waters, and freshwater wetlands is 1 to 39 kg N ha-1 y-1. This range spans the range of N deposition observed over most of the country. The empirical critical loads for N tend to increase in the following sequence for different life forms: diatoms, lichens and bryophytes, mycorrhizal fungi, herbaceous plants and shrubs, trees