Molecular Epidemiology of Influenza A/H3N2 Viruses Circulating in Mexico from 2003 to 2012

PubMed Central

Escalera-Zamudio, Marina; Nelson, Martha I.; Cobián Güemes, Ana Georgina; López-Martínez, Irma; Cruz-Ortiz, Natividad; Iguala-Vidales, Miguel; García, Elvia Rodríguez; Barrera-Badillo, Gisela; Díaz-Quiñonez, Jose Alberto; López, Susana; Arias, Carlos F.; Isa, Pavel

2014-01-01

In this work, nineteen influenza A/H3N2 viruses isolated in Mexico between 2003 and 2012 were studied. Our findings show that different human A/H3N2 viral lineages co-circulate within a same season and can also persist locally in between different influenza seasons, increasing the chance for genetic reassortment events. A novel minor cluster was also identified, named here as Korea, that circulated worldwide during 2003. Frequently, phylogenetic characterization did not correlate with the determined antigenic identity, supporting the need for the use of molecular evolutionary tools additionally to antigenic data for the surveillance and characterization of viral diversity during each flu season. This work represents the first long-term molecular epidemiology study of influenza A/H3N2 viruses in Mexico based on the complete genomic sequences and contributes to the monitoring of evolutionary trends of A/H3N2 influenza viruses within North and Central America. PMID:25075517

Global Migration Dynamics Underlie Evolution and Persistence of Human Influenza A (H3N2)

PubMed Central

Bedford, Trevor; Cobey, Sarah; Beerli, Peter; Pascual, Mercedes

2010-01-01

The global migration patterns of influenza viruses have profound implications for the evolutionary and epidemiological dynamics of the disease. We developed a novel approach to reconstruct the genetic history of human influenza A (H3N2) collected worldwide over 1998 to 2009 and used it to infer the global network of influenza transmission. Consistent with previous models, we find that China and Southeast Asia lie at the center of this global network. However, we also find that strains of influenza circulate outside of Asia for multiple seasons, persisting through dynamic migration between northern and southern regions. The USA acts as the primary hub of temperate transmission and, together with China and Southeast Asia, forms the trunk of influenza's evolutionary tree. These findings suggest that antiviral use outside of China and Southeast Asia may lead to the evolution of long-term local and potentially global antiviral resistance. Our results might also aid the design of surveillance efforts and of vaccines better tailored to different geographic regions. PMID:20523898

Persistent anomalies of the extratropical Northern Hemisphere wintertime circulation as an initiator of El Niño/Southern Oscillation events

DOE PAGES

Anderson, Bruce T.; Hassanzadeh, Pedram; Caballero, Rodrigo

2017-08-31

Climates across both hemispheres are strongly influenced by tropical Pacific variability associated with the El Niño/Southern Oscillation (ENSO). Conversely, extratropical variability also can affect the tropics. In particular, seasonal-mean alterations of near-surface winds associated with the North Pacific Oscillation (NPO) serve as a significant extratropical forcing agent of ENSO. However, it is still unclear what dynamical processes give rise to year-to-year shifts in these long-lived NPO anomalies. Here in this paper we show that intraseasonal variability in boreal winter pressure patterns over the Central North Pacific (CNP) imparts a significant signature upon the seasonal-mean circulations characteristic of the NPO. Furthermore » we show that the seasonal-mean signature results in part from year-to-year variations in persistent, quasi-stationary low-pressure intrusions into the subtropics of the CNP, accompanied by the establishment of persistent, quasi-stationary high-pressure anomalies over high latitudes of the CNP. Overall, we find that the frequency of these persistent extratropical anomalies (PEAs) during a given winter serves as a key modulator of intraseasonal variability in extratropical North Pacific circulations and, through their influence on the seasonal-mean circulations in and around the southern lobe of the NPO, the state of the equatorial Pacific 9–12 months later.« less

Persistent anomalies of the extratropical Northern Hemisphere wintertime circulation as an initiator of El Niño/Southern Oscillation events

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, Bruce T.; Hassanzadeh, Pedram; Caballero, Rodrigo

Climates across both hemispheres are strongly influenced by tropical Pacific variability associated with the El Niño/Southern Oscillation (ENSO). Conversely, extratropical variability also can affect the tropics. In particular, seasonal-mean alterations of near-surface winds associated with the North Pacific Oscillation (NPO) serve as a significant extratropical forcing agent of ENSO. However, it is still unclear what dynamical processes give rise to year-to-year shifts in these long-lived NPO anomalies. Here in this paper we show that intraseasonal variability in boreal winter pressure patterns over the Central North Pacific (CNP) imparts a significant signature upon the seasonal-mean circulations characteristic of the NPO. Furthermore » we show that the seasonal-mean signature results in part from year-to-year variations in persistent, quasi-stationary low-pressure intrusions into the subtropics of the CNP, accompanied by the establishment of persistent, quasi-stationary high-pressure anomalies over high latitudes of the CNP. Overall, we find that the frequency of these persistent extratropical anomalies (PEAs) during a given winter serves as a key modulator of intraseasonal variability in extratropical North Pacific circulations and, through their influence on the seasonal-mean circulations in and around the southern lobe of the NPO, the state of the equatorial Pacific 9–12 months later.« less

Decreased frequency and function of circulating plasmocytoid dendritic cells (pDC) in hepatitis B virus infected humans.

PubMed

Duan, Xue-Zhang; Wang, Min; Li, Han-Wei; Zhuang, Hui; Xu, Dongping; Wang, Fu-Sheng

2004-11-01

The Type 2 precursor plasmacytoid dendritic cells (pDC) represent the most important cell type in antiviral innate immunity. To understand the function of pDC during hepatitis B virus infection, the frequency and function of circulating pDC were analyzed by flow cytometric analysis, and IFN-alpha secretion of total PBMCs was determined by ELISA assay in 25 healthy subjects and 116 patients at various stages of chronic hepatitis B virus infection (CHB). The number of circulating pDC was found to be significantly lower in patients with CHB and associated liver cirrhosis (LC). The ability of PBMCs to secrete IFN-alpha also decreased significantly. There was a corresponding decrease of circulating NK cells and CD8+ T cells. We observed that lamuvidine antiviral therapy restored the number of circulating pDC and there was a reversal of pDC frequency with the control of HBV replication in chronic HBV patients, indicating these subjects are unlikely to be totally immunocompromised. The decrease of pDC was found to be related to nosocomial infections in LC patients. Our results suggest that CHB patients probably have a quantitative and qualitative impairment of circulating pDC or NK cells, which may be associated with HBV persistent infection as well as the nosocomial infections that arise in LC patients.

Mutation detection of E6 and LCR genes from HPV 16 associated with carcinogenesis.

PubMed

Mosmann, Jessica P; Monetti, Marina S; Frutos, Maria C; Kiguen, Ana X; Venezuela, Raul F; Cuffini, Cecilia G

2015-01-01

Human papillomavirus (HPV) is responsible for one of the most frequent sexually transmitted infections. The first phylogenetic analysis was based on a LCR region fragment. Nowadays, 4 variants are known: African (Af-1, Af-2), Asian-American (AA) and European (E). However the existence of sub-lineages of the European variant havs been proposed, specific mutations in the E6 and LCR sequences being possibly related to persistent viral infections. The aim of this study was a phylogenetic study of HPV16 sequences of endocervical samples from Cordoba, in order to detect the circulating lineages and analyze the presence of mutations that could be correlated with malignant disease. The phylogenetic analysis determined that 86% of the samples belonged to the E variant, 7% to AF-1 and the remaining 7% to AF-2. The most frequent mutation in LCR sequences was G7521A, in 80% of the analyzed samples; it affects the binding site of a transcription factor that could contribute to carcinogenesis. In the E6 sequences, the most common mutation was T350G (L83V), detected in 67% of the samples, associated with increased risk of persistent infection. The high detection rate of the European lineage correlated with patterns of human migration. This study emphasizes the importance of recognizing circulating lineages, as well as the detection of mutations associated with high-grade neoplastic lesions that could be correlated to the development of carcinogenic lesions.

L-form bacteria cohabitants in human blood: significance for health and diseases.

PubMed

Markova, Nadya D

2017-05-01

From a historical perspective, intriguing assumptions about unknown "live units" in human blood have attracted the attention of researchers, reflecting their desire to define a new class of microorganisms. Thus, the concept of "blood microbiota" brings about many questions about the nature, origin, and biological significance of the "unusual microbial cohabitants" in human blood. In contrast to current views that bloodstream in healthy humans is sterile, the hypothesis about the existence of microbes as L-forms (cell wall deficient bacteria) in human blood has evolved on the basis of known facts about their unique biology, as observed in our studies and those of other authors. Recently, we reported that bacterial L-forms persist in the human blood and that filterable, self-replicating bodies with a virus-like size of 100 nm are able to cross the maternal-fetal barrier by vertically transmitted pathway, then enter fetus blood circulation and colonize newborns. Subjects discussed here include the following: Is the existence of L-form bacteria in human blood a natural phenomenon? Are L-form bacteria commensal cohabitants in the human body? Since blood is an unfavorable compartment for the classical bacteria and their propagation, how do L-forms survive in blood circulation? How does L-form microbiota in blood influence the host immune system and contribute to systemic inflammatory, autoimmune, and tumor diseases? The current commentary presents the topic of "human microbiota and L-form bacteria" in its microcosm. It contains details of the hypothesis, supporting evidence and important implications.

Post-modification of preformed liposomes with novel non-phospholipid poly(ethylene glycol)-conjugated hexadecylcarbamoylmethyl hexadecanoic acid for enhanced circulation persistence in vivo

PubMed Central

Nag, Okhil K; Yadav, Vivek R; Hedrick, Andria; Awasthi, Vibhudutta

2013-01-01

We report synthesis and characterization of a novel PEG2000-conjugated hexadecylcarbamoylmethyl hexadecanoate (HDAS-PEG) as a PEG-phospholipid substitute for enhancing circulation persistence of liposomes. HDAS-PEG showed critical micelle concentration of 4.25 μM. We used post-insertion technique to introduce HDAS-PEG in outer lipid layer of the preformed liposomes. The presence of surface HDAS-PEG was confirmed by altered electrophoretic mobility, confocal microscopy and PEG estimation by ELISA. The post-inserted HDAS-PEG desorbed at approximately half the rate at which post-inserted DSPE-PEG desorbed from the liposome surface. HDAS-PEG significantly reduced liposome-induced complement activation (C4d, Bb and SC5b); HDAS-PEG was more effective than more commonly used DSPE-PEG in this capacity. For studying circulation persistence, the liposomes were labeled with 99mTc radionuclide and administered in rats. 99mTc-HDAS-PEG-liposomes showed prolonged persistence in blood as compared to that shown by 99mTc-plain liposomes. After 24 h of administration, < 1% of 99mTc-plain liposomes remained in blood, whereas approximately 28% of injected 99mTc-HDAS-PEG-liposomes were present in blood. In comparison, only 4.8% of 99mTc-DSPE-PEG-liposomes was measured in blood after 24 h. As expected, the clearance route of the liposomes was through liver and spleen. These results demonstrate the potential of a novel non-phosphoryl HDAS-PEG for surface modification of preformed liposomes with a goal of prolonging their circulation persistence and more effective inhibition of complement activation. PMID:23419666

Genomewide analysis of reassortment and evolution of human influenza A(H3N2) viruses circulating between 1968 and 2011.

PubMed

Westgeest, Kim B; Russell, Colin A; Lin, Xudong; Spronken, Monique I J; Bestebroer, Theo M; Bahl, Justin; van Beek, Ruud; Skepner, Eugene; Halpin, Rebecca A; de Jong, Jan C; Rimmelzwaan, Guus F; Osterhaus, Albert D M E; Smith, Derek J; Wentworth, David E; Fouchier, Ron A M; de Graaf, Miranda

2014-03-01

Influenza A(H3N2) viruses became widespread in humans during the 1968 H3N2 virus pandemic and have been a major cause of influenza epidemics ever since. These viruses evolve continuously by reassortment and genomic evolution. Antigenic drift is the cause for the need to update influenza vaccines frequently. Using two data sets that span the entire period of circulation of human influenza A(H3N2) viruses, it was shown that influenza A(H3N2) virus evolution can be mapped to 13 antigenic clusters. Here we analyzed the full genomes of 286 influenza A(H3N2) viruses from these two data sets to investigate the genomic evolution and reassortment patterns. Numerous reassortment events were found, scattered over the entire period of virus circulation, but most prominently in viruses circulating between 1991 and 1998. Some of these reassortment events persisted over time, and one of these coincided with an antigenic cluster transition. Furthermore, selection pressures and nucleotide and amino acid substitution rates of all proteins were studied, including those of the recently discovered PB1-N40, PA-X, PA-N155, and PA-N182 proteins. Rates of nucleotide and amino acid substitutions were most pronounced for the hemagglutinin, neuraminidase, and PB1-F2 proteins. Selection pressures were highest in hemagglutinin, neuraminidase, matrix 1, and nonstructural protein 1. This study of genotype in relation to antigenic phenotype throughout the period of circulation of human influenza A(H3N2) viruses leads to a better understanding of the evolution of these viruses. Each winter, influenza virus infects approximately 5 to 15% of the world's population, resulting in significant morbidity and mortality. Influenza A(H3N2) viruses evolve continuously by reassortment and genomic evolution. This leads to changes in antigenic recognition (antigenic drift) which make it necessary to update vaccines against influenza A(H3N2) viruses frequently. In this study, the relationship of genetic evolution to antigenic change spanning the entire period of A(H3N2) virus circulation was studied for the first time. The results presented in this study contribute to a better understanding of genetic evolution in correlation with antigenic evolution of influenza A(H3N2) viruses.

The genomic and epidemiological dynamics of human influenza A virus.

PubMed

Rambaut, Andrew; Pybus, Oliver G; Nelson, Martha I; Viboud, Cecile; Taubenberger, Jeffery K; Holmes, Edward C

2008-05-29

The evolutionary interaction between influenza A virus and the human immune system, manifest as 'antigenic drift' of the viral haemagglutinin, is one of the best described patterns in molecular evolution. However, little is known about the genome-scale evolutionary dynamics of this pathogen. Similarly, how genomic processes relate to global influenza epidemiology, in which the A/H3N2 and A/H1N1 subtypes co-circulate, is poorly understood. Here through an analysis of 1,302 complete viral genomes sampled from temperate populations in both hemispheres, we show that the genomic evolution of influenza A virus is characterized by a complex interplay between frequent reassortment and periodic selective sweeps. The A/H3N2 and A/H1N1 subtypes exhibit different evolutionary dynamics, with diverse lineages circulating in A/H1N1, indicative of weaker antigenic drift. These results suggest a sink-source model of viral ecology in which new lineages are seeded from a persistent influenza reservoir, which we hypothesize to be located in the tropics, to sink populations in temperate regions.

Insights Into Circulating Cytokine Dynamics during Pregnancy in HIV-Infected Beninese Exposed to Plasmodium falciparum Malaria

PubMed Central

Ibitokou, Samad A.; Denoeud-Ndam, Lise; Ezinmegnon, Sèm; Ladékpo, Rodolphe; Zannou, Djimon-Marcel; Massougbodji, Achille; Girard, Pierre-Marie; Cot, Michel; Luty, Adrian J. F.; Ndam, Nicaise Tuikue

2015-01-01

We investigated the circulating plasma levels of Th1- (Interleukin-2 [IL-2], tumor necrosis factor-α [TNF-α], interferon-gamma [IFN-γ]) and Th2-type (IL-4, IL-5, IL-10) cytokines in human immunodeficiency virus (HIV)-infected pregnant women living in a malaria-endemic area. We analyzed samples from 200 pregnant women included in the prevention of pregnancy-associated malaria in HIV-infected women: cotrimoxazole prophylaxis versus mefloquine (PACOME) clinical trial who were followed until delivery. Cytokine concentrations were measured by flow cytometry-based multiplex bead array. Significantly elevated levels of IL-10 and lower levels of TNF-α were observed at delivery compared with inclusion (P = 0.005). At inclusion, the presence of circulating IFN-γ, a higher CD4+ T cell count and having initiated intermittent preventive treatment of malaria with sulfadoxine pyrimethamine (SP-IPTp) were all associated with a lower likelihood of Plasmodium falciparum infection. At delivery, the inverse relationship between the presence of infection and circulating IFN-γ persisted, although there was a positive association between the likelihood of infection and the presence of circulating TNF-α. Initiation of antiretroviral therapy was associated with elevated IL-5 production. Consistent with our own and others' observations in HIV seronegative subjects, this study shows circulating IL-10 to be a marker of infection with P. falciparum during pregnancy even in HIV-infected women, although plasma IFN-γ may be a marker of anti-malarial protection in such women. PMID:26101276

Two Outbreak Sources of Influenza A (H7N9) Viruses Have Been Established in China.

PubMed

Wang, Dayan; Yang, Lei; Zhu, Wenfei; Zhang, Ye; Zou, Shumei; Bo, Hong; Gao, Rongbao; Dong, Jie; Huang, Weijuan; Guo, Junfeng; Li, Zi; Zhao, Xiang; Li, Xiaodan; Xin, Li; Zhou, Jianfang; Chen, Tao; Dong, Libo; Wei, Hejiang; Li, Xiyan; Liu, Liqi; Tang, Jing; Lan, Yu; Yang, Jing; Shu, Yuelong

2016-06-15

Due to enzootic infections in poultry and persistent human infections in China, influenza A (H7N9) virus has remained a public health threat. The Yangtze River Delta region, which is located in eastern China, is well recognized as the original source for H7N9 outbreaks. Based on the evolutionary analysis of H7N9 viruses from all three outbreak waves since 2013, we identified the Pearl River Delta region as an additional H7N9 outbreak source. H7N9 viruses are repeatedly introduced from these two sources to the other areas, and the persistent circulation of H7N9 viruses occurs in poultry, causing continuous outbreak waves. Poultry movements may contribute to the geographic expansion of the virus. In addition, the AnH1 genotype, which was predominant during wave 1, was replaced by JS537, JS18828, and AnH1887 genotypes during waves 2 and 3. The establishment of a new source and the continuous evolution of the virus hamper the elimination of H7N9 viruses, thus posing a long-term threat of H7N9 infection in humans. Therefore, both surveillance of H7N9 viruses in humans and poultry and supervision of poultry movements should be strengthened. Since its occurrence in humans in eastern China in spring 2013, the avian H7N9 viruses have been demonstrating the continuing pandemic threat posed by the current influenza ecosystem in China. As the viruses are silently circulated in poultry, with potentially severe outcomes in humans, H7N9 virus activity in humans in China is very important to understand. In this study, we identified a newly emerged H7N9 outbreak source in the Pearl River Delta region. Both sources in the Yangtze River Delta region and the Pearl River Delta region have been established and found to be responsible for the H7N9 outbreaks in mainland China. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Two Outbreak Sources of Influenza A (H7N9) Viruses Have Been Established in China

PubMed Central

Wang, Dayan; Yang, Lei; Zhu, Wenfei; Zhang, Ye; Zou, Shumei; Bo, Hong; Gao, Rongbao; Dong, Jie; Huang, Weijuan; Guo, Junfeng; Li, Zi; Zhao, Xiang; Li, Xiaodan; Xin, Li; Zhou, Jianfang; Chen, Tao; Dong, Libo; Wei, Hejiang; Li, Xiyan; Liu, Liqi; Tang, Jing; Lan, Yu; Yang, Jing

2016-01-01

ABSTRACT Due to enzootic infections in poultry and persistent human infections in China, influenza A (H7N9) virus has remained a public health threat. The Yangtze River Delta region, which is located in eastern China, is well recognized as the original source for H7N9 outbreaks. Based on the evolutionary analysis of H7N9 viruses from all three outbreak waves since 2013, we identified the Pearl River Delta region as an additional H7N9 outbreak source. H7N9 viruses are repeatedly introduced from these two sources to the other areas, and the persistent circulation of H7N9 viruses occurs in poultry, causing continuous outbreak waves. Poultry movements may contribute to the geographic expansion of the virus. In addition, the AnH1 genotype, which was predominant during wave 1, was replaced by JS537, JS18828, and AnH1887 genotypes during waves 2 and 3. The establishment of a new source and the continuous evolution of the virus hamper the elimination of H7N9 viruses, thus posing a long-term threat of H7N9 infection in humans. Therefore, both surveillance of H7N9 viruses in humans and poultry and supervision of poultry movements should be strengthened. IMPORTANCE Since its occurrence in humans in eastern China in spring 2013, the avian H7N9 viruses have been demonstrating the continuing pandemic threat posed by the current influenza ecosystem in China. As the viruses are silently circulated in poultry, with potentially severe outcomes in humans, H7N9 virus activity in humans in China is very important to understand. In this study, we identified a newly emerged H7N9 outbreak source in the Pearl River Delta region. Both sources in the Yangtze River Delta region and the Pearl River Delta region have been established and found to be responsible for the H7N9 outbreaks in mainland China. PMID:27030268

Weather conditions conducive to Beijing severe haze more frequent under climate change

NASA Astrophysics Data System (ADS)

Cai, Wenju; Li, Ke; Liao, Hong; Wang, Huijun; Wu, Lixin

2017-03-01

The frequency of Beijing winter severe haze episodes has increased substantially over the past decades, and is commonly attributed to increased pollutant emissions from China’s rapid economic development. During such episodes, levels of fine particulate matter are harmful to human health and the environment, and cause massive disruption to economic activities, as occurred in January 2013. Conducive weather conditions are an important ingredient of severe haze episodes, and include reduced surface winter northerlies, weakened northwesterlies in the midtroposphere, and enhanced thermal stability of the lower atmosphere. How such weather conditions may respond to climate change is not clear. Here we project a 50% increase in the frequency and an 80% increase in the persistence of conducive weather conditions similar to those in January 2013, in response to climate change. The frequency and persistence between the historical (1950-1999) and future (2050-2099) climate were compared in 15 models under Representative Concentration Pathway 8.5 (RCP8.5). The increased frequency is consistent with large-scale circulation changes, including an Arctic Oscillation upward trend, weakening East Asian winter monsoon, and faster warming in the lower troposphere. Thus, circulation changes induced by global greenhouse gas emissions can contribute to the increased Beijing severe haze frequency.

An Assessment of the Intestinal Lumen as a Site for Intervention in Reducing Body Burdens of Organochlorine Compounds

PubMed Central

Jandacek, Ronald J.; Genuis, Stephen J.

2013-01-01

Many individuals maintain a persistent body burden of organochlorine compounds (OCs) as well as other lipophilic compounds, largely as a result of airborne and dietary exposures. Ingested OCs are typically absorbed from the small intestine along with dietary lipids. Once in the body, stored OCs can mobilize from adipose tissue storage sites and, along with circulating OCs, are delivered into the small intestine via hepatic processing and biliary transport. Retained OCs are also transported into both the large and small intestinal lumen via non-biliary mechanisms involving both secretion and desquamation from enterocytes. OCs and some other toxicants can be reabsorbed from the intestine, however, they take part in enterohepatic circulation(EHC). While dietary fat facilitates the absorption of OCs from the small intestine, it has little effect on OCs within the large intestine. Non-absorbable dietary fats and fat absorption inhibitors, however, can reduce the re-absorption of OCs and other lipophiles involved in EHC and may enhance the secretion of these compounds into the large intestine—thereby hastening their elimination. Clinical studies are currently underway to determine the efficacy of using non-absorbable fats and inhibitors of fat absorption in facilitating the elimination of persistent body burdens of OCs and other lipophilic human contaminants. PMID:23476122

An assessment of the intestinal lumen as a site for intervention in reducing body burdens of organochlorine compounds.

PubMed

Jandacek, Ronald J; Genuis, Stephen J

2013-01-01

Many individuals maintain a persistent body burden of organochlorine compounds (OCs) as well as other lipophilic compounds, largely as a result of airborne and dietary exposures. Ingested OCs are typically absorbed from the small intestine along with dietary lipids. Once in the body, stored OCs can mobilize from adipose tissue storage sites and, along with circulating OCs, are delivered into the small intestine via hepatic processing and biliary transport. Retained OCs are also transported into both the large and small intestinal lumen via non-biliary mechanisms involving both secretion and desquamation from enterocytes. OCs and some other toxicants can be reabsorbed from the intestine, however, they take part in enterohepatic circulation(EHC). While dietary fat facilitates the absorption of OCs from the small intestine, it has little effect on OCs within the large intestine. Non-absorbable dietary fats and fat absorption inhibitors, however, can reduce the re-absorption of OCs and other lipophiles involved in EHC and may enhance the secretion of these compounds into the large intestine--thereby hastening their elimination. Clinical studies are currently underway to determine the efficacy of using non-absorbable fats and inhibitors of fat absorption in facilitating the elimination of persistent body burdens of OCs and other lipophilic human contaminants.

Persistent lymphadenopathy in homosexual men: a clinical and ultrastructural study.

PubMed

Anderson, M G; Dixey, J; Key, P; Ellis, D S; Tovey, G; McCaul, T F; Murray-Lyon, I M; Gazzard, B; Lawrence, A; Evans, B

1984-04-21

Ultrastructural changes (tubuloreticular structures and tube and ring shaped forms) previously described in patients with acquired immunodeficiency syndrome (AIDS) are described for the first time in the lymph nodes and circulating lymphocytes of patients with persistent lymphadenopathy. These observations support the view that the persistent lymphadenopathy syndrome and AIDS are caused by the same transmissible agent(s).

Recombination events and variability among full-length genomes of co-circulating molluscum contagiosum virus subtypes 1 and 2.

PubMed

López-Bueno, Alberto; Parras-Moltó, Marcos; López-Barrantes, Olivia; Belda, Sylvia; Alejo, Alí

2017-05-01

Molluscum contagiosum virus (MCV) is the sole member of the Molluscipoxvirus genus and causes a highly prevalent human disease of the skin characterized by the formation of a variable number of lesions that can persist for prolonged periods of time. Two major genotypes, subtype 1 and subtype 2, are recognized, although currently only a single complete genomic sequence corresponding to MCV subtype 1 is available. Using next-generation sequencing techniques, we report the complete genomic sequence of four new MCV isolates, including the first one derived from a subtype 2. Comparisons suggest a relatively distant evolutionary split between both MCV subtypes. Further, our data illustrate concurrent circulation of distinct viruses within a population and reveal the existence of recombination events among them. These results help identify a set of MCV genes with potentially relevant roles in molluscum contagiosum epidemiology and pathogenesis.

Low circulating ghrelin levels in women with polycystic ovary syndrome: a systematic review and meta-analysis

PubMed Central

Gao, Tian; Wu, Lang; Chang, Fuhou; Cao, Guifang

2016-01-01

Although numerous, human subject studies evaluating the relationship between circulating ghrelin levels and polycystic ovary syndrome (PCOS) risk have yielded inconsistent findings. We aimed to quantitatively assess the association by summarizing all available evidence from human subject studies. The PubMed and Web of Science databases were searched up to February 2015 for eligible studies. Studies were eligible if they reported circulating ghrelin levels in women with PCOS and healthy women controls. A fixed or random-effects model was used to pool risk estimations. Twenty studies including 894 PCOS patients and 574 controls were included in the meta-analysis. The studies had fair methodological quality. The pooling analysis of all available studies revealed that ghrelin levels were significantly lower in PCOS patients than in controls, with standardized mean difference of −0.40 (95% CI: −0.73, −0.08). The significant association persisted in many subgroup strata. However, the heterogeneity across studies was considerable and not eliminated in subgroup analyses. Meta-regression analysis further suggested that the heterogeneity might be relevant to variability in study location, PCOS relevant factors like HOMA-IR ratio, as well as other factors not assessed. In conclusion, our meta-analysis suggested that ghrelin levels were significantly lower in PCOS patients than in controls. Further studies with large sample sizes are warranted to replicate our findings. PMID:26607017

Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: potential for group housing.

PubMed

Jensen, Vivi Flou Hjorth; Mølck, Anne-Marie; Mårtensson, Martin; Strid, Mette Aagaard; Chapman, Melissa; Lykkesfeldt, Jens; Bøgh, Ingrid Brück

2017-06-01

Group housing is considered to be important for rats, which are highly sociable animals. Single housing may impact behaviour and levels of circulating stress hormones. Rats are typically used in the toxicological evaluation of insulin analogues. Human insulin (HI) is frequently used as a reference compound in these studies, and a comparator model of persistent exposure by HI infusion from external pumps has recently been developed to support toxicological evaluation of long-acting insulin analogues. However, this model requires single housing of the animals. Developing an insulin-infusion model which allows group housing would therefore greatly improve animal welfare. The aim of the present study was to investigate the suitability of implantable infusion pumps for HI infusion in group-housed rats. Group housing of rats implanted with a battery-driven pump proved to be possible. Intravenous infusion of HI lowered blood glucose levels persistently for two weeks, providing a comparator model for use in two-week repeated-dose toxicity studies with new long-acting insulin analogues, which allows group housing, and thereby increasing animal welfare compared with an external infusion model.

The persistent prevalence and evolution of cross-family recombinant coronavirus GCCDC1 among a bat population: a two-year follow-up.

PubMed

Obameso, Joseph O; Li, Hong; Jia, Hao; Han, Min; Zhu, Shiyan; Huang, Canping; Zhao, Yuhui; Zhao, Min; Bai, Yu; Yuan, Fei; Zhao, Honglan; Peng, Xia; Xu, Wen; Tan, Wenjie; Zhao, Yingze; Yuen, Kwok-Yung; Liu, William J; Lu, Lin; Gao, George F

2017-12-01

Bats are connected with the increasing numbers of emerging and re-emerging viruses that may break the species barrier and spread into the human population. Coronaviruses are one of the most common viruses discovered in bats, which were considered as the natural source of recent human-susceptible coronaviruses, i.e. SARS-COV and MERS-CoV. Our previous study reported the discovery of a bat-derived putative cross-family recombinant coronavirus with a reovirus gene p10, named as Ro-BatCoV GCCDC1. In this report, through a two-year follow-up of a special bat population in one specific cave of south China, we illustrate that Ro-BatCoV GCCDC1 persistently circulates among bats. Notably, through the longitudinal observation, we identified the dynamic evolution of Ro-BatCoV GCCDC1 in bats represented by continuously recombination events. Our study provides the first glimpse of the virus evolution in one longitudinally observed bat population cohort and underlines the surveillance and pre-warning of potential interspecies transmittable viruses in bats.

Progress toward interrupting wild poliovirus circulation in countries with reestablished transmission--Africa, 2009-2010.

PubMed

2011-03-18

Through efforts of the Global Polio Eradication Initiative (GPEI), begun in 1988, indigenous transmission of wild poliovirus (WPV) had been interrupted in all but four countries (Afghanistan, Pakistan, India, and Nigeria) by 2006. Since 2002, a total of 39 previously polio-free countries experienced outbreaks following importation of WPV of Indian or Nigerian origin. Most outbreaks were stopped <6 months after confirmation. However, circulation in Angola, Chad, Democratic Republic of the Congo (DRC), and Sudan persisted >12 months following importation before 2009. A key milestone of the GPEI 2010-2012 strategic plan was to interrupt WPV transmission in these African countries with reestablished transmission by the end of 2010. As of March 8, 2011, the milestone appeared to be on track only in Sudan. In Sudan, WPV type 1 (WPV1) was introduced in 2004, but no cases were detected for a 31-month period during 2005-2008. When resurgence occurred in 2008, surveillance and eradication efforts were enhanced, and no case has been detected since June 2009. In Chad, WPV type 3 (WPV3) transmission has persisted since 2007, although undetected for 7 months in 2010. In Angola, WPV1 circulation has persisted following importation in 2007, and became more widespread in 2010, with subsequent importations into DRC and Republic of the Congo (ROC). In DRC, WPV1 circulation has persisted since introduction in 2006. Achieving polio eradication depends on stopping WPV transmission in the four endemic countries and overcoming substantial, ongoing programmatic weaknesses in Chad, Angola, and DRC.

Successive Respiratory Syncytial Virus Epidemics in Local Populations Arise from Multiple Variant Introductions, Providing Insights into Virus Persistence

PubMed Central

Otieno, James R.; Ngama, Mwanajuma; Mwihuri, Alexander G.; Medley, Graham F.; Cane, Patricia A.; Nokes, D. James

2015-01-01

ABSTRACT Respiratory syncytial virus (RSV) is a global respiratory pathogen of humans, with infection occurring characteristically as recurrent seasonal epidemics. Unlike influenza viruses, little attention has been paid to the mechanism underlying worldwide spread and persistence of RSV and how this may be discerned through an improved understanding of the introduction and persistence of RSV in local communities. We analyzed 651 attachment (G) glycoprotein nucleotide sequences of RSV B collected over 11 epidemics (2002 to 2012) in Kilifi, Kenya, and contemporaneous data collected elsewhere in Kenya and 18 other countries worldwide (2002 to 2012). Based on phylogeny, genetic distance and clustering patterns, we set out pragmatic criteria to classify local viruses into distinct genotypes and variants, identifying those newly introduced and those locally persisting. Three genotypes were identified in the Kilifi data set: BA (n = 500), SAB1 (n = 148), and SAB4 (n = 3). Recurrent RSV epidemics in the local population were composed of numerous genetic variants, most of which have been newly introduced rather than persisting in the location from season to season. Global comparison revealed that (i) most Kilifi variants do not cluster closely with strains from outside Kenya, (ii) some Kilifi variants were closely related to those observed outside Kenya (mostly Western Europe), and (iii) many variants were circulating elsewhere but were never detected in Kilifi. These results are consistent with the hypothesis that year-to-year presence of RSV at the local level (i.e., Kilifi) is achieved primarily, but not exclusively, through introductions from a pool of variants that are geographically restricted (i.e., to Kenya or to the region) rather than global. IMPORTANCE The mechanism by which RSV persists and reinvades local populations is poorly understood. We investigated this by studying the temporal patterns of RSV variants in a rural setting in tropical Africa and comparing these variants with contemporaneous variants circulating in other countries. We found that periodic seasonal RSV transmission at the local level appears to require regular new introductions of variants. However, importantly, the evidence suggests that the source of new variants is mostly geographically restricted, and we hypothesize that year-to-year RSV persistence is at the country level rather than the global level. This has implications for control. PMID:26355091

Exposure to non-persistent pesticides and thyroid function: A systematic review of epidemiological evidence.

PubMed

Campos, Élida; Freire, Carmen

2016-08-01

Numerous pesticides are recognized for their endocrine-disrupting properties. Non-persistent pesticides such as organophosphates, dithiocarbamates and pyrethroids may interfere with thyroid function as suggested by animal studies. However, the influence of chronic exposure to these compounds on thyroidal functions in humans remains to be determined. The present study aimed to review epidemiological evidence for an association between exposure to non-persistent pesticides and circulating levels of thyroid hormones (thyroxin [T4] and triiodothyronine [T3]) and thyroid-stimulating hormone (TSH). A systematic review was conducted using MEDLINE, SCOPUS and Virtual Health Library (BVS) databases. Articles were limited to original studies and reports published in English, Portuguese or Spanish. Nineteen epidemiological studies were identified, 17 of which were cross-sectional, 14 were of occupationally exposed workers and 11 used exposure biomarkers. Fungicides and organophosphates (OP) insecticides were the most studied pesticides. Although methodological heterogeneity between studies was noted, particularly regarding study design, exposure assessment, and control of confounding, most of them showed associations with changes in T3 and T4, and/or TSH levels, while results from a few of these are consistent with experimental data supporting the findings that non-persistent pesticide exposure exerts hypothyroid-like effects. However, reporting quality was moderate to poor in 50% of the studies, particularly regarding method of selection of participants and discussion of external validity. Overall, current knowledge regarding the impact of non-persistent pesticides on human thyroid function is still limited. Given the widespread use of pesticides, future research should assess effects of exposure to currently-used pesticides in cohort studies combining comprehensive questionnaire-based assessment and biomarkers. Investigators need to pay particular attention to exposure during critical windows of brain development and exposure in agricultural populations. Copyright © 2016 Elsevier GmbH. All rights reserved.

Metabolic fate of polyphenols in the human superorganism

PubMed Central

van Duynhoven, John; Vaughan, Elaine E.; Jacobs, Doris M.; Kemperman, Robèr A.; van Velzen, Ewoud J. J.; Gross, Gabriele; Roger, Laure C.; Possemiers, Sam; Smilde, Age K.; Doré, Joël; Westerhuis, Johan A.; Van de Wiele, Tom

2011-01-01

Dietary polyphenols are components of many foods such as tea, fruit, and vegetables and are associated with several beneficial health effects although, so far, largely based on epidemiological studies. The intact forms of complex dietary polyphenols have limited bioavailability, with low circulating levels in plasma. A major part of the polyphenols persists in the colon, where the resident microbiota produce metabolites that can undergo further metabolism upon entering systemic circulation. Unraveling the complex metabolic fate of polyphenols in this human superorganism requires joint deployment of in vitro and humanized mouse models and human intervention trials. Within these systems, the variation in diversity and functionality of the colonic microbiota can increasingly be captured by rapidly developing microbiomics and metabolomics technologies. Furthermore, metabolomics is coming to grips with the large biological variation superimposed on relatively subtle effects of dietary interventions. In particular when metabolomics is deployed in conjunction with a longitudinal study design, quantitative nutrikinetic signatures can be obtained. These signatures can be used to define nutritional phenotypes with different kinetic characteristics for the bioconversion capacity for polyphenols. Bottom-up as well as top-down approaches need to be pursued to link gut microbial diversity to functionality in nutritional phenotypes and, ultimately, to bioactivity of polyphenols. This approach will pave the way for personalization of nutrition based on gut microbial functionality of individuals or populations. PMID:20615997

Whole-Genome Sequencing and Variant Analysis of Human Papillomavirus 16 Infections.

PubMed

van der Weele, Pascal; Meijer, Chris J L M; King, Audrey J

2017-10-01

Human papillomavirus (HPV) is a strongly conserved DNA virus, high-risk types of which can cause cervical cancer in persistent infections. The most common type found in HPV-attributable cancer is HPV16, which can be subdivided into four lineages (A to D) with different carcinogenic properties. Studies have shown HPV16 sequence diversity in different geographical areas, but only limited information is available regarding HPV16 diversity within a population, especially at the whole-genome level. We analyzed HPV16 major variant diversity and conservation in persistent infections and performed a single nucleotide polymorphism (SNP) comparison between persistent and clearing infections. Materials were obtained in the Netherlands from a cohort study with longitudinal follow-up for up to 3 years. Our analysis shows a remarkably large variant diversity in the population. Whole-genome sequences were obtained for 57 persistent and 59 clearing HPV16 infections, resulting in 109 unique variants. Interestingly, persistent infections were completely conserved through time. One reinfection event was identified where the initial and follow-up samples clustered differently. Non-A1/A2 variants seemed to clear preferentially ( P = 0.02). Our analysis shows that population-wide HPV16 sequence diversity is very large. In persistent infections, the HPV16 sequence was fully conserved. Sequencing can identify HPV16 reinfections, although occurrence is rare. SNP comparison identified no strongly acting effect of the viral genome affecting HPV16 infection clearance or persistence in up to 3 years of follow-up. These findings suggest the progression of an early HPV16 infection could be host related. IMPORTANCE Human papillomavirus 16 (HPV16) is the predominant type found in cervical cancer. Progression of initial infection to cervical cancer has been linked to sequence properties; however, knowledge of variants circulating in European populations, especially with longitudinal follow-up, is limited. By sequencing a number of infections with known follow-up for up to 3 years, we gained initial insights into the genetic diversity of HPV16 and the effects of the viral genome on the persistence of infections. A SNP comparison between sequences obtained from clearing and persistent infections did not identify strongly acting DNA variations responsible for these infection outcomes. In addition, we identified an HPV16 reinfection event where sequencing of initial and follow-up samples showed different HPV16 variants. Based on conventional genotyping, this infection would incorrectly be considered a persistent HPV16 infection. In the context of vaccine efficacy and monitoring studies, such infections could potentially cause reduced reported efficacy or efficiency. Copyright © 2017 van der Weele et al.

Comparative analysis of the Rotarix™ vaccine strain and G1P[8] rotaviruses detected before and after vaccine introduction in Belgium.

PubMed

Zeller, Mark; Heylen, Elisabeth; Tamim, Sana; McAllen, John K; Kirkness, Ewen F; Akopov, Asmik; De Coster, Sarah; Van Ranst, Marc; Matthijnssens, Jelle

2017-01-01

G1P[8] rotaviruses are responsible for the majority of human rotavirus infections worldwide. The effect of universal mass vaccination with rotavirus vaccines on circulating G1P[8] rotaviruses is still poorly understood. Therefore we analyzed the complete genomes of the Rotarix™ vaccine strain, and 70 G1P[8] rotaviruses, detected between 1999 and 2010 in Belgium (36 before and 34 after vaccine introduction) to investigate the impact of rotavirus vaccine introduction on circulating G1P[8] strains. All rotaviruses possessed a complete Wa-like genotype constellation, but frequent intra-genogroup reassortments were observed as well as multiple different cluster constellations circulating in a single season. In addition, identical cluster constellations were found to circulate persistently over multiple seasons. The Rotarix™ vaccine strain possessed a unique cluster constellation that was not present in currently circulating G1P[8] strains. At the nucleotide level, the VP6, VP2 and NSP2 gene segments of Rotarix™ were relatively distantly related to any Belgian G1P[8] strain, but other gene segments of Rotarix™ were found in clusters also containing circulating Belgian strains. At the amino acid level, the genetic distance between Rotarix™ and circulating Belgian strains was considerably lower, except for NSP1. When we compared the Belgian G1P[8] strains collected before and after vaccine introduction a reduction in the proportion of strains that were found in the same cluster as the Rotarix™ vaccine strain was observed for most gene segments. The reduction in the proportion of strains belonging to the same cluster may be the result of the vaccine introduction, although natural fluctuations cannot be ruled out.

Physical climate response to a reduction of anthropogenic climate forcing

NASA Astrophysics Data System (ADS)

Myneni, R. B.; Samanta, A.; Anderson, B. T.; Ganguly, S.; Knyazikhin, Y.; Nemani, R. R.

2009-12-01

Recent research indicates that the warming of the climate system resulting from increased greenhouse gas (GHG) emissions over the next century will persist for many centuries after the cessation of these emissions, due principally to the persistence of elevated atmospheric carbon dioxide (CO2) concentrations and their attendant radiative forcing. However, it is unknown whether the responses of other components of the climate system—including those related to Greenland and Antarctic ice cover, the Atlantic thermohaline circulation, the West African monsoon, and ecosystems and human welfare—would be reversed even if atmospheric CO2 concentrations were to recover to 1990 levels. Here, using a simple set of experiments employing a current-generation numerical climate model, we show that many physical characteristics of the climate system, including global temperatures, precipitation, soil moisture and sea ice, recover as CO2 concentrations decrease. In contrast, stratospheric water vapor, especially in the high latitudes, exhibits non-linear hysteresis. In these regions, increases in water vapor, which initially result from increased CO2 concentrations, remain present even as CO2 concentrations recover. This result has implications for the sensitivity of the global climate system, the evolution and recovery of stratospheric ozone, and the persistence of weather patterns in the high latitudes. Our work also demonstrates that further identification of threshold behavior in response to human-induced global climate change requires an examination of the full Earth system, including cryosphere, biosphere, and chemistry.

Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats.

PubMed

Miller, Desinia B; Snow, Samantha J; Henriquez, Andres; Schladweiler, Mette C; Ledbetter, Allen D; Richards, Judy E; Andrews, Debora L; Kodavanti, Urmila P

2016-09-01

Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25ppm or 1.00ppm ozone, 5h/day, 3 consecutive days/week (wk) for 13wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13wk or following a 1wk recovery period (13wk+1wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13wk, however, these responses were largely reversible following a 1wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism. Published by Elsevier Inc.

Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats☆,☆☆

PubMed Central

Miller, Desinia B.; Snow, Samantha J.; Henriquez, Andres; Schladweiler, Mette C.; Ledbetter, Allen D.; Richards, Judy E.; Andrews, Debora L.; Kodavanti, Urmila P.

2017-01-01

Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25 ppm or 1.00 ppm ozone, 5 h/day, 3 consecutive days/week (wk) for 13 wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13 wk or following a 1 wk recovery period (13 wk + 1 wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13 wk, however, these responses were largely reversible following a 1 wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism. PMID:27368153

Spatiotemporal dynamics of Puumala hantavirus associated with its rodent host, Myodes glareolus

PubMed Central

Weber de Melo, Vanessa; Sheikh Ali, Hanan; Freise, Jona; Kühnert, Denise; Essbauer, Sandra; Mertens, Marc; Wanka, Konrad M; Drewes, Stephan; Ulrich, Rainer G; Heckel, Gerald

2015-01-01

Many viruses significantly impact human and animal health. Understanding the population dynamics of these viruses and their hosts can provide important insights for epidemiology and virus evolution. Puumala virus (PUUV) is a European hantavirus that may cause regional outbreaks of hemorrhagic fever with renal syndrome in humans. Here, we analyzed the spatiotemporal dynamics of PUUV circulating in local populations of its rodent reservoir host, the bank vole (Myodes glareolus) during eight years. Phylogenetic and population genetic analyses of all three genome segments of PUUV showed strong geographical structuring at a very local scale. There was a high temporal turnover of virus strains in the local bank vole populations, but several virus strains persisted through multiple years. Phylodynamic analyses showed no significant changes in the local effective population sizes of PUUV, although vole numbers and virus prevalence fluctuated widely. Microsatellite data demonstrated also a temporally persisting subdivision between local vole populations, but these groups did not correspond to the subdivision in the virus strains. We conclude that restricted transmission between vole populations and genetic drift play important roles in shaping the genetic structure and temporal dynamics of PUUV in its natural host which has several implications for zoonotic risks of the human population. PMID:26136821

Antitumor effects and persistence of a novel HER2 CAR T cells directed to gastric cancer in preclinical models

PubMed Central

Han, Yali; Liu, Chuanyong; Li, Guanhua; Li, Juan; Lv, Xingyan; Shi, Huan; Liu, Jie; Liu, Shuai; Yan, Peng; Wang, Shuyun; Sun, Yuping; Sun, Meili

2018-01-01

New immunotherapeutic approaches are urgently needed for gastric cancer due to its poor survival and unsatisfactory treatment. Here we applied the humanized chA21 scfv based chimeric antigen receptor (CAR) modified T cells approach to the HER2 overexpressing gastric cancer treatment. The chA21-4-1BBz CAR T cells specifically exerted Th1 skewed cytokine response and efficient cytolysis of HER2 overexpressing human gastric cancer cells in vitro. Both the cytokine production and cytotoxicity levels were correlated with the level of HER2 surface expression by tumor cells. In established subcutaneous xenograft and peritoneal metastasis models, chA21-4-1BBz CAR T cells dramatically facilitated regression of HER2 overexpressing tumor and prolonged survival of tumor-bearing mice, whereas spared the progression of HER2 low-expressing tumor. Additionally, the capability of these CAR T cells to persist in circulation, as well as specifically home to, and accumulate in tumor sites were identified. Taken together, these results provide the basis for the future clinical investigation of the humanized chA21 scFv based, 4-1BB costimulated CAR T cells for the treatment of gastric cancer, and other HER2-expressing solid tumors. PMID:29416924

Local persistence and global dissemination play a significant role in the circulation of influenza B viruses in Leyte Island, Philippines.

PubMed

Furuse, Yuki; Odagiri, Takashi; Tamaki, Raita; Kamigaki, Taro; Otomaru, Hirono; Opinion, Jamie; Santo, Arlene; Dolina-Lacaba, Donna; Daya, Edgard; Okamoto, Michiko; Saito-Obata, Mariko; Inobaya, Marianette; Tan, Alvin; Tallo, Veronica; Lupisan, Socorro; Suzuki, Akira; Oshitani, Hitoshi

2016-05-01

The local and global transmission dynamics of influenza B virus is not completely understood mainly because of limited epidemiological and sequence data for influenza B virus. Here we report epidemiological and molecular characteristics of influenza B viruses from 2010 to 2013 in Leyte Island, Philippines. Phylogenetic analyses showed global dissemination of the virus among both neighboring and distant areas. The analyses also suggest that southeast Asia is not a distributor of influenza B virus and can introduce the virus from other areas. Furthermore, we found evidence on the local persistence of the virus over years in the Philippines. Taken together, both local persistence and global dissemination play a significant role in the circulation of influenza B virus. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

B cell depleting therapy regulates splenic and circulating T follicular helper cells in immune thrombocytopenia.

PubMed

Audia, Sylvain; Rossato, Marzia; Trad, Malika; Samson, Maxime; Santegoets, Kim; Gautheron, Alexandrine; Bekker, Cornelis; Facy, Olivier; Cheynel, Nicolas; Ortega-Deballon, Pablo; Boulin, Mathieu; Berthier, Sabine; Leguy-Seguin, Vanessa; Martin, Laurent; Ciudad, Marion; Janikashvili, Nona; Saas, Philippe; Radstake, Timothy; Bonnotte, Bernard

2017-02-01

B cells are involved in immune thrombocytopenia (ITP) pathophysiology by producing antiplatelet auto-antibodies. However more than a half of ITP patients do not respond to B cell depletion induced by rituximab (RTX). The persistence of splenic T follicular helper cells (TFH) that we demonstrated to be expanded during ITP and to support B cell differentiation and antiplatelet antibody-production may participate to RTX inefficiency. Whereas it is well established that the survival of TFH depends on B cells in animal models, nothing is known in humans yet. To determine the effect of B cell depletion on human TFH, we quantified B cells and TFH in the spleen and in the blood from ITP patients treated or not with RTX. We showed that B cell depletion led to a dramatic decrease in splenic TFH and in CXCL13 and IL-21, two cytokines predominantly produced by TFH. The absolute count of circulating TFH and serum CXCL13 also decreased after RTX treatment, whatever the therapeutic response. Therefore, we showed that the maintenance of TFH required B cells and that TFH are not involved in the inefficiency of RTX in ITP. Copyright © 2016 Elsevier Ltd. All rights reserved.

Persistent sample circulation microextraction combined with graphite furnace atomic absorption spectroscopy for trace determination of heavy metals in fish species marketed in Kermanshah, Iran, and human health risk assessment.

PubMed

Safari, Yahya; Karimaei, Mostafa; Sharafi, Kiomars; Arfaeinia, Hossein; Moradi, Masoud; Fattahi, Nazir

2018-06-01

Persistent sample circulation microextraction (PSCME) combined with graphite furnace atomic absorption spectrometry (GFAAS) was developed as a high pre-concentration technique for the determination of heavy metals in fish species. In this method, a few microliters of organic solvent (40.0 µL carbon tetrachloride) was transferred to the bottom of a conical sample cup. Then 10.0 mL of aqueous solution was transformed to fine droplets while passing through the organic solvent. At this stage, metal-ligand hydrophobic complex was extracted into the organic solvent. After extraction, 20 µL of extraction solvent was injected into the graphite tube using an auto-sampler. Under optimal conditions, enrichment factors and enhancement factor were in the range of 180-240 and 155-214, respectively. The calibration curves were linear in the range of 0.03-200 µg kg -1 and the limits of detection (LODs) were in the range of 0.01-0.05 µg kg -1 . Repeatability (intra-day) and reproducibility (inter-day) for 0.50 µg L -1 Hg and 0.10 µg L -1 Cd and Pb were in the range of 3.1-4.2% (n = 7) and 4.3-6.1% (n = 7), respectively. Potential human health risk assessment was conducted by calculating estimated weekly intake (EWI) of the metals from eating fish and comparison of these values with provisional tolerable weekly intake (PTWI) values. EWI data for the studied metals through fish consumption were lower than the PTWI values. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Hyperbiofilm Formation by Bordetella pertussis Strains Correlates with Enhanced Virulence Traits

PubMed Central

Cattelan, Natalia; Jennings-Gee, Jamie; Dubey, Purnima

2017-01-01

ABSTRACT Pertussis, or whooping cough, caused by the obligate human pathogen Bordetella pertussis is undergoing a worldwide resurgence. The majority of studies of this pathogen are conducted with laboratory-adapted strains which may not be representative of the species as a whole. Biofilm formation by B. pertussis plays an important role in pathogenesis. We conducted a side-by-side comparison of the biofilm-forming abilities of the prototype laboratory strains and the currently circulating isolates from two countries with different vaccination programs. Compared to the reference strain, all strains examined herein formed biofilms at high levels. Biofilm structural analyses revealed country-specific differences, with strains from the United States forming more structured biofilms. Bacterial hyperaggregation and reciprocal expression of biofilm-promoting and -inhibitory factors were observed in clinical isolates. An association of increased biofilm formation with augmented epithelial cell adhesion and higher levels of bacterial colonization in the mouse nose and trachea was detected. To our knowledge, this work links for the first time increased biofilm formation in bacteria with a colonization advantage in an animal model. We propose that the enhanced biofilm-forming capacity of currently circulating strains contributes to their persistence, transmission, and continued circulation. PMID:28893915

Primary immunodeficiencies predisposed to Epstein-Barr virus-driven haematological diseases.

PubMed

Parvaneh, Nima; Filipovich, Alexandra H; Borkhardt, Arndt

2013-09-01

Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, maintains lifelong subclinical persistent infections in humans. In the circulation, EBV primarily infects the B cells, and protective immunity is mediated by EBV-specific cytotoxic T cells (CTLs) and natural killer (NK) cells. However, EBV has been linked to several devastating diseases, such as haemophagocytic lymphohistiocytosis (HLH) and lymphoproliferative diseases in the immunocompromised host. Some types of primary immunodeficiencies (PIDs) are characterized by the development of EBV-associated complications as their predominant clinical feature. The study of such genetic diseases presents an ideal opportunity for a better understanding of the biology of the immune responses against EBV. Here, we summarize the range of PIDs that are predisposed to EBV-associated haematological diseases, describing their clinical picture and pathogenetic mechanisms. © 2013 John Wiley & Sons Ltd.

Rice production systems and avian influenza: Interactions between mixed-farming systems, poultry and wild birds

USGS Publications Warehouse

Muzaffar, S.B.; Takekawa, John Y.; Prosser, D.J.; Newman, S.H.; Xiao, X.

2010-01-01

Wild waterfowl are the reservoir for avian influenza viruses (AIVs), a family of RNA viruses that may cause mild sickness in waterbirds. Emergence of H5N1, a highly pathogenic avian influenza (HPAI) strain, causing severe disease and mortality in wild birds, poultry and humans, had raised concerns about the role of wild birds in possible transmission of the disease. In this review, the link between rice production systems, poultry production systems, and wild bird ecology is examined to assess the extent to which these interactions could contribute towards the persistence and evolution of HPAI H5N1. The rice (Oryza sativa) and poultry production systems in Asia described, and then migration and movements of wild birds discussed. Mixed farming systems in Asia and wild bird movement and migration patterns create opportunities for the persistence of low pathogenic AIVs in these systems. Nonetheless, there is no evidence of long-term persistence of HPAI viruses (including the H5N1 subtype) in the wild. There are still significant gaps in the understanding of how AIVs circulate in rice systems. A better understanding of persistence of AIVs in rice farms, particularly of poultry origins, is essential in limiting exchange of AIVs between mixed-farming systems, poultry and wild birds.

Persistent Places and Paths on the Middle Western Plain.

ERIC Educational Resources Information Center

Borchert, John R.

1986-01-01

Briefly sketches the origin and persistence of the Midwest as a physical, city-centered circulation and settlement system drawing from physical, cultural, economic, and applied specialties within geography. Illustrates the coherence of the specialties within a regional-historical framework with basic geographic/scientific problems of scale,…

Changes in the hemagglutinin of H5N1 viruses during human infection – Influence on receptor binding☆

PubMed Central

Crusat, Martin; Liu, Junfeng; Palma, Angelina S.; Childs, Robert A.; Liu, Yan; Wharton, Stephen A.; Lin, Yi Pu; Coombs, Peter J.; Martin, Stephen R.; Matrosovich, Mikhail; Chen, Zi; Stevens, David J.; Hien, Vo Minh; Thanh, Tran Tan; Nhu, Le Nguyen Truc; Nguyet, Lam Anh; Ha, Do Quang; van Doorn, H.Rogier; Hien, Tran Tinh; Conradt, Harald S.; Kiso, Makoto; Gamblin, Steve J.; Chai, Wengang; Skehel, John J.; Hay, Alan J.; Farrar, Jeremy; de Jong, Menno D.; Feizi, Ten

2013-01-01

As avian influenza A(H5N1) viruses continue to circulate in Asia and Africa, global concerns of an imminent pandemic persist. Recent experimental studies suggest that efficient transmission between humans of current H5N1 viruses only requires a few genetic changes. An essential step is alteration of the virus hemagglutinin from preferential binding to avian receptors for the recognition of human receptors present in the upper airway. We have identified receptor-binding changes which emerged during H5N1 infection of humans, due to single amino acid substitutions, Ala134Val and Ile151Phe, in the hemagglutinin. Detailed biological, receptor-binding, and structural analyses revealed reduced binding of the mutated viruses to avian-like receptors, but without commensurate increased binding to the human-like receptors investigated, possibly reflecting a receptor-binding phenotype intermediate in adaptation to more human-like characteristics. These observations emphasize that evolution in nature of avian H5N1 viruses to efficient binding of human receptors is a complex multistep process. PMID:24050651

Effect of Anesthesia Carrier Gas on In-Vivo Circulation Times of Ultrasound Microbubble Contrast Agents in Rats

PubMed Central

Mullin, Lee; Gessner, Ryan; Kwan, James; Kaya, Mehmet; Borden, Mark A.; Dayton, Paul A.

2012-01-01

Purpose Microbubble contrast agents are currently implemented in a variety of both clinical and preclinical ultrasound imaging studies. The therapeutic and diagnostic capabilities of these contrast agents are limited by their short in-vivo lifetimes, and research to lengthen their circulation times is ongoing. In this manuscript, observations are presented from a controlled experiment performed to evaluate differences in circulation times for lipid shelled perfluorocarbon-filled contrast agents circulating within rodents as a function of inhaled anesthesia carrier gas. Methods The effects of two common anesthesia carrier gas selections - pure oxygen and medical air – were observed within five rats. Contrast agent persistence within the kidney was measured and compared for oxygen and air anesthesia carrier gas for six bolus contrast injections in each animal. Simulations were performed to examine microbubble behavior with changes in external environment gases. Results A statistically significant extension of contrast circulation time was observed for animals breathing medical air compared to breathing pure oxygen. Simulations support experimental observations and indicate that enhanced contrast persistence may be explained by reduced ventilation/perfusion mismatch and classical diffusion, in which nitrogen plays a key role by contributing to the volume and diluting other gas species in the microbubble gas core. Conclusion: Using medical air in place of oxygen as the carrier gas for isoflurane anesthesia can increase the circulation lifetime of ultrasound microbubble contrast agents. PMID:21246710

Predictive thresholds for plague in Kazakhstan.

PubMed

Davis, Stephen; Begon, Mike; De Bruyn, Luc; Ageyev, Vladimir S; Klassovskiy, Nikolay L; Pole, Sergey B; Viljugrein, Hildegunn; Stenseth, Nils Chr; Leirs, Herwig

2004-04-30

In Kazakhstan and elsewhere in central Asia, the bacterium Yersinia pestis circulates in natural populations of gerbils, which are the source of human cases of bubonic plague. Our analysis of field data collected between 1955 and 1996 shows that plague invades, fades out, and reinvades in response to fluctuations in the abundance of its main reservoir host, the great gerbil (Rhombomys opimus). This is a rare empirical example of the two types of abundance thresholds for infectious disease-invasion and persistence- operating in a single wildlife population. We parameterized predictive models that should reduce the costs of plague surveillance in central Asia and thereby encourage its continuance.

The Asian house shrew Suncus murinus as a reservoir and source of human outbreaks of plague in Madagascar.

PubMed

Rahelinirina, Soanandrasana; Rajerison, Minoarisoa; Telfer, Sandra; Savin, Cyril; Carniel, Elisabeth; Duplantier, Jean-Marc

2017-11-01

Identifying key reservoirs for zoonoses is crucial for understanding variation in incidence. Plague re-emerged in Mahajanga, Madagascar in the 1990s but there has been no confirmed case since 1999. Here we combine ecological and genetic data, from during and after the epidemics, with experimental infections to examine the role of the shrew Suncus murinus in the plague epidemiological cycle. The predominance of S. murinus captures during the epidemics, their carriage of the flea vector and their infection with Yersinia pestis suggest they played an important role in the maintenance and transmission of plague. S. murinus exhibit a high but variable resistance to experimental Y. pestis infections, providing evidence of its ability to act as a maintenance host. Genetic analyses of the strains isolated from various hosts were consistent with two partially-linked transmission cycles, with plague persisting within the S. murinus population, occasionally spilling over into the rat and human populations. The recent isolation from a rat in Mahajanga of a Y. pestis strain genetically close to shrew strains obtained during the epidemics reinforces this hypothesis and suggests circulation of plague continues. The observed decline in S. murinus and Xenopsylla cheopis since the epidemics appears to have decreased the frequency of spillover events to the more susceptible rats, which act as a source of infection for humans. Although this may explain the lack of confirmed human cases in recent years, the current circulation of plague within the city highlights the continuing health threat.

Molecular Epidemiology of Oyster-Related Human Noroviruses and Their Global Genetic Diversity and Temporal-Geographical Distribution from 1983 to 2014

PubMed Central

Yu, Yongxin; Cai, Hui; Hu, Linghao; Lei, Rongwei; Pan, Yingjie; Yan, Shuling

2015-01-01

Noroviruses (NoVs) are a leading cause of epidemic and sporadic cases of acute gastroenteritis worldwide. Oysters are well recognized as the main vectors of environmentally transmitted NoVs, and disease outbreaks linked to oyster consumption have been commonly observed. Here, to quantify the genetic diversity, temporal distribution, and circulation of oyster-related NoVs on a global scale, 1,077 oyster-related NoV sequences deposited from 1983 to 2014 were downloaded from both NCBI GenBank and the NoroNet outbreak database and were then screened for quality control. A total of 665 sequences with reliable information were obtained and were subsequently subjected to genotyping and phylogenetic analyses. The results indicated that the majority of oyster-related NoV sequences were obtained from coastal countries and regions and that the numbers of sequences in these regions were unevenly distributed. Moreover, >80% of human NoV genotypes were detected in oyster samples or oyster-related outbreaks. A higher proportion of genogroup I (GI) (34%) was observed for oyster-related sequences than for non-oyster-related outbreaks, where GII strains dominated with an overwhelming majority of >90%, indicating that the prevalences of GI and GII are different in humans and oysters. In addition, a related convergence of the circulation trend was found between oyster-related NoV sequences and human pandemic outbreaks. This suggests that oysters not only act as a vector of NoV through environmental transmission but also serve as an important reservoir of human NoVs. These results highlight the importance of oysters in the persistence and transmission of human NoVs in the environment and have important implications for the surveillance of human NoVs in oyster samples. PMID:26319869

Extracting quasi-steady Lagrangian transport patterns from the ocean circulation: An application to the Gulf of Mexico.

PubMed

Duran, R; Beron-Vera, F J; Olascoaga, M J

2018-03-26

We construct a climatology of Lagrangian coherent structures (LCSs)-the concealed skeleton that shapes transport-with a twelve-year-long data-assimilative simulation of the sea-surface circulation in the Gulf of Mexico (GoM). Computed as time-mean Cauchy-Green strain tensorlines of the climatological velocity, the climatological LCSs (cLCSs) unveil recurrent Lagrangian circulation patterns. The cLCSs strongly constrain the ensemble-mean Lagrangian circulation of the instantaneous model velocity, showing that a climatological velocity can preserve meaningful transport information. The quasi-steady transport patterns revealed by the cLCSs agree well with aspects of the GoM circulation described in several previous observational and numerical studies. For example, the cLCSs identify regions of persistent isolation, and suggest that coastal regions previously identified as high-risk for pollution impact are regions of maximal attraction. We also show that cLCSs are remarkably accurate at identifying transport patterns observed during the Deepwater Horizon and Ixtoc oil spills, and during the Grand LAgrangian Deployment (GLAD) experiment. Thus it is shown that computing cLCSs is an efficient and meaningful way of synthesizing vast amounts of Lagrangian information. The cLCS method confirms previous GoM studies, and contributes to our understanding by revealing the persistent nature of the dynamics and kinematics treated therein.

Persistence of Circulating Hepatitis C Virus Antigens-Specific Immune Complexes in Patients with Resolved HCV Infection.

PubMed

Hu, Ke-Qin; Cui, Wei

2018-05-01

Our recent study indicated the possible presence of detectable hepatitis C virus antigens (HCV-Ags) after denaturation of sera with resolved HCV (R-HCV) infection. The present study determined and characterized persistent HCV-Ags-specific immune complexes (ICs) in these patients. Sixty-eight sera with R-HCV and 34 with viremic HCV (V-HCV) infection were tested for free and IC-bound HCV-Ags using HCV-Ags enzyme immunoassay (EIA), the presence of HCV-Ags-specific ICs by immunoprecipitation and Western blot (IP-WB), HCV ICs containing HCV virions using IP and HCV RNA RT-PCR, and correlation of HCV ICs with clinical presentation in these patients. Using HCV-Ags EIA, we found 57.4% of sera with R-HCV infection were tested positive for bound, but not free HCV-Ags. Using pooled or individual anti-HCV E1/E2, cAg, NS3, NS4b, and/or NS5a to precipitate HCV-specific-Ags, we confirmed persistent HCV-Ags ICs specific to various HCV structural and non-structural proteins not only in V-HCV infection, but also in R-HCV infection. Using IP and HCV RNA PCR, we then confirmed the presence of HCV virions within circulating ICs in V-HCV, but not in R-HCV sera. Multivariable analysis indicated significant and independent associations of persistent circulating HCV-Ags-specific ICs with both age and the presence of cirrhosis in patients with R-HCV infection. Various HCV-Ag-specific ICs, but not virions, persist in 57.4% of patients who had spontaneous or treatment-induced HCV clearance for 6 months to 20 years. These findings enriched our knowledge on HCV pathogenesis and support further study on its long-term clinical relevance, such as extrahepatic manifestation, transfusion medicine, and hepatocarcinogenesis.

Divergent human origin influenza viruses detected in Australian swine populations.

PubMed

Wong, Frank Y K; Donato, Celeste; Deng, Yi-Mo; Teng, Don; Komadina, Naomi; Baas, Chantal; Modak, Joyanta; O'Dea, Mark; Smith, David W; Effler, Paul V; Cooke, Julie; Davies, Kelly R; Hurt, Aeron; Kung, Nina; Levy, Avram; Loh, Richmond; Shan, Songhua; Shinwari, Mustaghfira W; Stevens, Vittoria; Taylor, Joanne; Williams, David T; Watson, James; Eagles, Debbie; McCullough, Sam; Barr, Ian G; Dhanasekaran, Vijaykrishna

2018-06-06

Global swine populations infected with influenza A viruses pose a persistent pandemic risk. With the exception of a few countries, our understanding of the genetic diversity of swine influenza viruses is limited, hampering control measures and pandemic risk assessment. Here we report the genomic characteristics and evolutionary history of influenza A viruses isolated in Australia during 2012-2016 from two geographically isolated swine populations in the states of Queensland and Western Australia. Phylogenetic analysis with an expansive human and swine influenza virus dataset comprising >40,000 sequences sampled globally, revealed evidence of the pervasive introduction and long-term establishment of gene segments derived from several human influenza viruses of past seasons, including H1N1/1977, H1N1/1995, H3N2/1968, H3N2/2003, and H1N1pdm09, and a genotype that contained gene segments derived from the past three pandemics (1968, re-emerged 1977 and 2009). Of the six human-derived gene lineages only one comprising two viruses isolated in Queensland during 2012 was closely related to swine viruses detected from other regions, indicating a previously undetected circulation of Australian swine lineages for approximately 3-44 years. Although the date of introduction of these lineages into Australian swine populations could not be accurately ascertained, we found evidence of sustained transmission of two lineages in swine during 2012-2016. The continued detection of human-origin influenza virus lineages in swine over several decades with little or unpredictable antigenic drift indicates that isolated swine populations can act as 'antigenic archives' of human influenza, raising the risk of re-emergence in humans when sufficient susceptible populations arise. IMPORTANCE We described the evolutionary origins and antigenic properties of influenza A viruses isolated from two separate Australian swine populations during 2012-2016, showing that these viruses were distinct to each other and to those isolated from swine globally. Whole genome sequencing of virus isolates revealed a high genotypic diversity that had been generated exclusively through the introduction and establishment of human influenza viruses that circulated in past seasons. We detected six reassortants with gene segments derived from human H1N1/H1N1pdm09 and various human H3N2 viruses that circulated at various periods since 1968. We also found that these swine viruses were not related to swine viruses collected elsewhere indicating independent circulation. The detection of unique lineages and genotypes in Australia suggests that isolated swine populations that are sufficiently large can sustain influenza for extensive periods, we showed direct evidence of a sustained transmission for at least 4 years between 2012-2016. Copyright © 2018 American Society for Microbiology.

High Prevalence of Human Parvovirus B19 DNA in Myocardial Autopsy Samples from Subjects without Myocarditis or Dilative Cardiomyopathy▿

PubMed Central

Schenk, Thomas; Enders, Martin; Pollak, Stefan; Hahn, Ralph; Huzly, Daniela

2009-01-01

Human parvovirus B19 has been linked to a variety of cardiac diseases, as well as to erythema infectiosum, acute arthropathy, and fetal hydrops. A causal association between viral infection and cardiac disease was frequently postulated following the detection of B19 DNA by PCR in endomyocardial biopsy specimens. Since the lifelong persistence of B19 DNA in bone marrow, skin, synovia, tonsils, and liver was previously reported, the aim of our study was to investigate the possibility of asymptomatic B19 DNA persistence in heart tissue. Myocardial autopsy and postmortem blood samples were prospectively collected from 69 bodies sent to the Department of Forensic Medicine, Freiburg University Medical Center, for inquests. All study subjects were screened for B19-specific antibodies using a commercial enzyme immunoassay. Tissue samples were analyzed by real-time PCR for the presence of viral DNA. Since the presence of B19 genotype 2, known to have been circulating before 1960, would prove long-lasting persistence, the presence of the B19 genotype was retrospectively determined in seven of the study subjects by melting temperature analysis and sequencing of the PCR product. B19 DNA was found in myocardial samples from 46 of 48 seropositive and in none of 21 seronegative individuals. B19 genotype 1 was found in three patients born between 1950 and 1969. Genotype 2 was found in four patients born between 1927 and 1957. Our findings suggest lifelong persistence of B19 DNA in heart tissue. Thus, the detection of B19 DNA in myocardial biopsy specimens alone is not sufficient to postulate a relationship between B19 infection and cardiac disease. PMID:19005147

Differential blood flow responses to CO2 in human internal and external carotid and vertebral arteries

PubMed Central

Sato, Kohei; Sadamoto, Tomoko; Hirasawa, Ai; Oue, Anna; Subudhi, Andrew W; Miyazawa, Taiki; Ogoh, Shigehiko

2012-01-01

Arterial CO2 serves as a mediator of cerebral blood flow (CBF), and its relative influence on the regulation of CBF is defined as cerebral CO2 reactivity. Our previous studies have demonstrated that there are differences in CBF responses to physiological stimuli (i.e. dynamic exercise and orthostatic stress) between arteries in humans. These findings suggest that dynamic CBF regulation and cerebral CO2 reactivity may be different in the anterior and posterior cerebral circulation. The aim of this study was to identify cerebral CO2 reactivity by measuring blood flow and examine potential differences in CO2 reactivity between the internal carotid artery (ICA), external carotid artery (ECA) and vertebral artery (VA). In 10 healthy young subjects, we evaluated the ICA, ECA, and VA blood flow responses by duplex ultrasonography (Vivid-e, GE Healthcare), and mean blood flow velocity in middle cerebral artery (MCA) and basilar artery (BA) by transcranial Doppler (Vivid-7, GE healthcare) during two levels of hypercapnia (3% and 6% CO2), normocapnia and hypocapnia to estimate CO2 reactivity. To characterize cerebrovascular reactivity to CO2, we used both exponential and linear regression analysis between CBF and estimated partial pressure of arterial CO2, calculated by end-tidal partial pressure of CO2. CO2 reactivity in VA was significantly lower than in ICA (coefficient of exponential regression 0.021 ± 0.008 vs. 0.030 ± 0.008; slope of linear regression 2.11 ± 0.84 vs. 3.18 ± 1.09% mmHg−1: VA vs. ICA, P < 0.01). Lower CO2 reactivity in the posterior cerebral circulation was persistent in distal intracranial arteries (exponent 0.023 ± 0.006 vs. 0.037 ± 0.009; linear 2.29 ± 0.56 vs. 3.31 ± 0.87% mmHg−1: BA vs. MCA). In contrast, CO2 reactivity in ECA was markedly lower than in the intra-cerebral circulation (exponent 0.006 ± 0.007; linear 0.63 ± 0.64% mmHg−1, P < 0.01). These findings indicate that vertebro-basilar circulation has lower CO2 reactivity than internal carotid circulation, and that CO2 reactivity of the external carotid circulation is markedly diminished compared to that of the cerebral circulation, which may explain different CBF responses to physiological stress. PMID:22526884

Human Myeloid-derived Suppressor Cells are Associated With Chronic Immune Suppression After Severe Sepsis/Septic Shock.

PubMed

Mathias, Brittany; Delmas, Amber L; Ozrazgat-Baslanti, Tezcan; Vanzant, Erin L; Szpila, Benjamin E; Mohr, Alicia M; Moore, Frederick A; Brakenridge, Scott C; Brumback, Babette A; Moldawer, Lyle L; Efron, Philip A

2017-04-01

We hypothesized that after sepsis in humans, MDSCs will be persistently increased, functionally immunosuppressive, and associated with adverse clinical outcomes. Cancer and sepsis have surprisingly similar immunologic responses and equally dismal long term consequences. In cancer, increased myeloid-derived suppressor cells (MDSCs) induce detrimental immunosuppression, but little is known about the role of MDSCs after sepsis. Blood was obtained from 74 patients within 12 hours of severe sepsis/septic shock (SS/SS), and at set intervals out to 28 days, and also in 18 healthy controls. MDSCs were phenotyped for cell surface receptor expression and enriched by cell sorting. Functional and genome-wide expression analyses were performed. Multiple logistic regression analysis was conducted to determine if increased MDSC appearance was associated with in-hospital and long-term outcomes. After SS/SS, CD33CD11bHLA-DR MDSCs were dramatically increased out to 28 days (P < 0.05). When co-cultured with MDSCs from SS/SS patients, antigen-driven T-cell proliferation and TH1/TH2 cytokine production were suppressed (P < 0.05). Additionally, septic MDSCs had suppressed HLA gene expression and up-regulated ARG1 expression (P < 0.05). Finally, SS/SS patients with persistent increased percentages of blood MDSCs had increased nosocomial infections, prolonged intensive care unit stays, and poor functional status at discharge (P < 0.05). After SS/SS in humans, circulating MDSCs are persistently increased, functionally immunosuppressive, and associated with adverse outcomes. This novel observation warrants further studies. As observed in cancer immunotherapy, MDSCs could be a novel component in multimodality immunotherapy targeting detrimental inflammation and immunosuppression after SS/SS to improve currently observed dismal long-term outcomes.

Helper-dependent adenovirus achieve more efficient and persistent liver transgene expression in non-human primates under immunosuppression.

PubMed

Unzu, C; Melero, I; Hervás-Stubbs, S; Sampedro, A; Mancheño, U; Morales-Kastresana, A; Serrano-Mendioroz, I; de Salamanca, R E; Benito, A; Fontanellas, A

2015-11-01

Helper-dependent adenoviral (HDA) vectors constitute excellent gene therapy tools for metabolic liver diseases. We have previously shown that an HDA vector encoding human porphobilinogen deaminase (PBGD) corrects acute intermittent porphyria mice. Now, six non-human primates were injected in the left hepatic lobe with the PBGD-encoding HDA vector to study levels and persistence of transgene expression. Intrahepatic administration of 5 × 10(12) viral particles kg(-1) (10(10) infective units kg(-1)) of HDA only resulted in transient (≈14 weeks) transgene expression in one out of three individuals. In contrast, a more prolonged 90-day immunosuppressive regimen (tacrolimus, mycophenolate, rituximab and steroids) extended meaningful transgene expression for over 76 weeks in two out of two cases. Transgene expression under immunosuppression (IS) reached maximum levels 6 weeks after HDA administration and gradually declined reaching a stable plateau within the therapeutic range for acute porphyria. The non-injected liver lobes also expressed the transgene because of vector circulation. IS controlled anticapsid T-cell responses and decreased the induction of neutralizing antibodies. Re-administration of HDA-hPBGD at week +78 achieved therapeutically meaningful transgene expression only in those animals receiving IS again at the time of this second vector exposure. Overall, immunity against adenoviral capsids poses serious hurdles for long-term HDA-mediated liver transduction, which can be partially circumvented by pharmacological IS.

Autonomic neural control of dynamic cerebral autoregulation in humans

NASA Technical Reports Server (NTRS)

Zhang, Rong; Zuckerman, Julie H.; Iwasaki, Kenichi; Wilson, Thad E.; Crandall, Craig G.; Levine, Benjamin D.

2002-01-01

BACKGROUND: The purpose of the present study was to determine the role of autonomic neural control of dynamic cerebral autoregulation in humans. METHODS AND RESULTS: We measured arterial pressure and cerebral blood flow (CBF) velocity in 12 healthy subjects (aged 29+/-6 years) before and after ganglion blockade with trimethaphan. CBF velocity was measured in the middle cerebral artery using transcranial Doppler. The magnitude of spontaneous changes in mean blood pressure and CBF velocity were quantified by spectral analysis. The transfer function gain, phase, and coherence between these variables were estimated to quantify dynamic cerebral autoregulation. After ganglion blockade, systolic and pulse pressure decreased significantly by 13% and 26%, respectively. CBF velocity decreased by 6% (P<0.05). In the very low frequency range (0.02 to 0.07 Hz), mean blood pressure variability decreased significantly (by 82%), while CBF velocity variability persisted. Thus, transfer function gain increased by 81%. In addition, the phase lead of CBF velocity to arterial pressure diminished. These changes in transfer function gain and phase persisted despite restoration of arterial pressure by infusion of phenylephrine and normalization of mean blood pressure variability by oscillatory lower body negative pressure. CONCLUSIONS: These data suggest that dynamic cerebral autoregulation is altered by ganglion blockade. We speculate that autonomic neural control of the cerebral circulation is tonically active and likely plays a significant role in the regulation of beat-to-beat CBF in humans.

Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts

PubMed Central

Ramirez-Carvajal, Lisbeth; Pauszek, Steven J.; Ahmed, Zaheer; Farooq, Umer; Naeem, Khalid; Shabman, Reed S.; Stockwell, Timothy B.; Rodriguez, Luis L.

2018-01-01

Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008–2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008–2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region. PMID:29390015

Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts.

PubMed

Ramirez-Carvajal, Lisbeth; Pauszek, Steven J; Ahmed, Zaheer; Farooq, Umer; Naeem, Khalid; Shabman, Reed S; Stockwell, Timothy B; Rodriguez, Luis L

2018-01-01

Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008-2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008-2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region.

Proof-of-concept study: profile of circulating micro RNAs in bovine serum harvested during acute and persistent FMDV infection

USDA-ARS?s Scientific Manuscript database

Expression of 144 distinct bovine microRNAs (miRNAs) was quantified in bovine serum harvested during different phases of infection with foot-and-mouth disease virus (FMDV). There were marked differences in miRNA expression between acute, persistent, and convalescent phases of infection. During acu...

Differential Protein Expression Marks the Transition From Infection With Opisthorchis viverrini to Cholangiocarcinoma*

PubMed Central

Khoontawad, Jarinya; Pairojkul, Chawalit; Rucksaken, Rucksak; Pinlaor, Porntip; Wongkham, Chaisiri; Yongvanit, Puangrat; Pugkhem, Ake; Jones, Alun; Plieskatt, Jordan; Potriquet, Jeremy; Bethony, Jeffery; Pinlaor, Somchai; Mulvenna, Jason

2017-01-01

Parts of Southeast Asia have the highest incidence of intrahepatic cholangiocarcinoma (CCA) in the world because of infection by the liver fluke Opisthorchis viverrini (Ov). Ov-associated CCA is the culmination of chronic Ov-infection, with the persistent production of the growth factors and cytokines associated with persistent inflammation, which can endure for years in Ov-infected individuals prior to transitioning to CCA. Isobaric labeling and tandem mass spectrometry of liver tissue from a hamster model of CCA was used to compare protein expression profiles from inflammed tissue (Ovinfected but not cancerous) versus cancerous tissue (Ov-induced CCA). Immunohistochemistry and immunoblotting were used to verify dysregulated proteins in the animal model and in human tissue. We identified 154 dysregulated proteins that marked the transition from Ov-infection to Ov-induced CCA, i.e. proteins dysregulated during carcinogenesis but not Ov-infection. The verification of dysregulated proteins in resected liver tissue from humans with Ov-associated CCA showed the numerous parallels in protein dysregulation between human and animal models of Ov-induced CCA. To identify potential circulating markers for CCA, dysregulated proteins were compared with proteins isolated from exosomes secreted by a human CCA cell line (KKU055) and 27 proteins were identified as dysregulated in CCA and present in exosomes. These data form the basis of potential diagnostic biomarkers for human Ov-associated CCA. The profile of protein dysregulation observed during chronic Ovinfection and then in Ov-induced CCA provides insight into the etiology of an infection-induced inflammation-related cancer. PMID:28232516

Human immunodeficiency virus/human parvovirus B19 co-infection in blood donors and AIDS patients in Sichuan, China

PubMed Central

He, Miao; Zhu, Jiang; Yin, Huimin; Ke, Ling; Gao, Lei; Pan, Zhihong; Yang, Xiuhua; Li, Wuping

2012-01-01

Background Human parvovirus B19 (B19) is a common pathogen which causes a variety of diseases. Persistent B19 infection is related to the degree of host immunodeficiency in patients with human immunodeficiency virus (HIV) infection. However, the existence, loading, virus evolution and distribution of B19 in Chinese HIV-positive patients have not been determined. Materials and methods. We investigated 573 HIV-positive blood donors and AIDS patients in Sichuan, China in the last two decades. Bl9-specific serology and quantitative polymerase chain reaction were used to determine the prevalence of B19/HIV co-infection. Viral genome fragments were subjected to phylogeny and haplotype analysis. Results B19 genomic DNA was found in 26 of 573 (4.5%) HIV-positive individuals, a higher prevalence than in blood donors. DNA levels ranged from 5.3×102–1.1×105 copies/mL. The seroprevalence of IgG was significantly lower in HIV-positive samples than in HIV-negative blood donors, indicating deficient production of B19-specific IgG in the former. The B19 isolates were genotype-1 subtype B19-1A which formed a monophyletic group; seven distinct haplotypes were discovered with 60% of the B19/HIV co-infected variants sharing one central haplotype. Discussion. This study on the prevalence, phylogeny and distribution of human parvovirus B19 in Sichuan, China, demonstrates the persistence of B19 in the circulation of both immunocompetent and immunocompromised subjects, with implications for blood safety. PMID:22790259

Environmental levels, toxicity and human exposure to tributyltin (TBT)-contaminated marine environment. a review. b_antizar@hotmail.com.

PubMed

Antizar-Ladislao, Blanca

2008-02-01

Tributyltin (TBT) is a toxic chemical used for various industrial purposes such as slime control in paper mills, disinfection of circulating industrial cooling waters, antifouling agents, and the preservation of wood. Due to its widespread use as an antifouling agent in boat paints, TBT is a common contaminant of marine and freshwater ecosystems exceeding acute and chronic toxicity levels. TBT is the most significant pesticide in marine and freshwaters in Europe and consequently its environmental level, fate, toxicity and human exposure are of current concern. Thus, the European Union has decided to specifically include TBT compounds in its list of priority compounds in water in order to control its fate in natural systems, due to their toxic, persistent, bioaccumulative and endocrine disruptive characteristics. Additionally, the International Maritime Organization has called for a global treaty that bans the application of TBT-based paints starting 1 of January 2003, and total prohibition by 1 of January 2008. This paper reviews the state of the science regarding TBT, with special attention paid to the environmental levels, toxicity, and human exposure. TBT compounds have been detected in a number of environmental samples. In humans, organotin compounds have been detected in blood and in the liver. As for other persistent organic pollutants, dietary intake is most probably the main route of exposure to TBT compounds for the general population. However, data concerning TBT levels in foodstuffs are scarce. It is concluded that investigations on experimental toxicity, dietary intake, potential human health effects and development of new sustainable technologies to remove TBT compounds are clearly necessary.

Splenectomy Is Modifying the Vascular Remodeling of Thrombosis

PubMed Central

Frey, Maria K.; Alias, Sherin; Winter, Max P.; Redwan, Bassam; Stübiger, Gerald; Panzenboeck, Adelheid; Alimohammadi, Arman; Bonderman, Diana; Jakowitsch, Johannes; Bergmeister, Helga; Bochkov, Valery; Preissner, Klaus T.; Lang, Irene M.

2014-01-01

Background Splenectomy is a clinical risk factor for complicated thrombosis. We hypothesized that the loss of the mechanical filtering function of the spleen may enrich for thrombogenic phospholipids in the circulation, thereby affecting the vascular remodeling of thrombosis. Methods and Results We investigated the effects of splenectomy both in chronic thromboembolic pulmonary hypertension (CTEPH), a human model disease for thrombus nonresolution, and in a mouse model of stagnant flow venous thrombosis mimicking deep vein thrombosis. Surgically excised thrombi from rare cases of CTEPH patients who had undergone previous splenectomy were enriched for anionic phospholipids like phosphatidylserine. Similar to human thrombi, phosphatidylserine accumulated in thrombi after splenectomy in the mouse model. A postsplenectomy state was associated with larger and more persistent thrombi. Higher counts of procoagulant platelet microparticles and increased leukocyte–platelet aggregates were observed in mice after splenectomy. Histological inspection revealed a decreased number of thrombus vessels. Phosphatidylserine‐enriched phospholipids specifically inhibited endothelial proliferation and sprouting. Conclusions After splenectomy, an increase in circulating microparticles and negatively charged phospholipids is enhanced by experimental thrombus induction. The initial increase in thrombus volume after splenectomy is due to platelet activation, and the subsequent delay of thrombus resolution is due to inhibition of thrombus angiogenesis. The data illustrate a potential mechanism of disease in CTEPH. PMID:24584745

The Impact of Low-Level Cloud Feedback on Persistent Changes in Atmospheric Circulation in the Pacific

NASA Astrophysics Data System (ADS)

Burgman, R.; Kirtman, B. P.; Clement, A. C.; Vazquez, H.

2017-12-01

Recent studies suggest that low clouds in the Pacific play an important role in the observed decadal climate variability and future climate change. In this study, we implement a novel modeling experiment designed to isolate how interactions between local and remote feedbacks associated with low cloud, SSTs, and the largescale circulation play a significant role in the observed persistence of tropical Pacific SST and associated North American drought. The modeling approach involves the incorporation of observed patterns of satellite-derived shortwave cloud radiative effect (SWCRE) into the coupled model framework and is ideally suited for examining the role of local and large-scale coupled feedbacks and ocean heat transport in Pacific decadal variability. We show that changes in SWCRE forcing in eastern subtropical Pacific alone reproduces much of the observed changes in SST and atmospheric circulation over the past 16 years, including the observed changes in precipitation over much of the Western Hemisphere.

Winter to winter recurrence of atmospheric circulation anomalies over East Asia and its impact on winter surface air temperature anomalies

PubMed Central

2017-01-01

The persistence of atmospheric circulation anomalies over East Asia shows a winter to winter recurrence (WTWR) phenomenon. Seasonal variations in sea level pressure anomalies and surface wind anomalies display significantly different characteristics between WTWR and non-WTWR years. The WTWR years are characterized by the recurrence of both a strong (weak) anomalous Siberian High and an East Asian winter monsoon over two successive winters without persistence through the intervening summer. However, anomalies during the non-WTWR years have the opposite sign between the current and ensuing winters. The WTWR of circulation anomalies contributes to that of surface air temperature anomalies (SATAs), which is useful information for improving seasonal and interannual climate predictions over East Asia and China. In the positive (negative) WTWR years, SATAs are cooler (warmer) over East Asia in two successive winters, but the signs of the SATAs are opposite in the preceding and subsequent winters during the non-WTWR years. PMID:28178351

Winter to winter recurrence of atmospheric circulation anomalies over East Asia and its impact on winter surface air temperature anomalies.

PubMed

Zhao, Xia; Yang, Guang

2017-01-01

The persistence of atmospheric circulation anomalies over East Asia shows a winter to winter recurrence (WTWR) phenomenon. Seasonal variations in sea level pressure anomalies and surface wind anomalies display significantly different characteristics between WTWR and non-WTWR years. The WTWR years are characterized by the recurrence of both a strong (weak) anomalous Siberian High and an East Asian winter monsoon over two successive winters without persistence through the intervening summer. However, anomalies during the non-WTWR years have the opposite sign between the current and ensuing winters. The WTWR of circulation anomalies contributes to that of surface air temperature anomalies (SATAs), which is useful information for improving seasonal and interannual climate predictions over East Asia and China. In the positive (negative) WTWR years, SATAs are cooler (warmer) over East Asia in two successive winters, but the signs of the SATAs are opposite in the preceding and subsequent winters during the non-WTWR years.

Summers with low Arctic sea ice linked to persistence of spring atmospheric circulation patterns

NASA Astrophysics Data System (ADS)

Kapsch, Marie-Luise; Skific, Natasa; Graversen, Rune G.; Tjernström, Michael; Francis, Jennifer A.

2018-05-01

The declining trend of Arctic September sea ice constitutes a significant change in the Arctic climate system. Large year-to-year variations are superimposed on this sea-ice trend, with the largest variability observed in the eastern Arctic Ocean. Knowledge of the processes important for this variability may lead to an improved understanding of seasonal and long-term changes. Previous studies suggest that transport of heat and moisture into the Arctic during spring enhances downward surface longwave radiation, thereby controlling the annual melt onset, setting the stage for the September ice minimum. In agreement with these studies, we find that years with a low September sea-ice concentration (SIC) are characterized by more persistent periods in spring with enhanced energy flux to the surface in forms of net longwave radiation plus turbulent fluxes, compared to years with a high SIC. Two main atmospheric circulation patterns related to these episodes are identified: one resembles the so-called Arctic dipole anomaly that promotes transport of heat and moisture from the North Pacific, whereas the other is characterized by negative geopotential height anomalies over the Arctic, favoring cyclonic flow from Siberia and the Kara Sea into the eastern Arctic Ocean. However, differences between years with low and high September SIC appear not to be due to different spring circulation patterns; instead it is the persistence and intensity of processes associated with these patterns that distinguish the two groups of anomalous years: Years with low September SIC feature episodes that are consistently stronger and more persistent than years with high SIC.

2.1 Natural History of Highly Pathogenic Avian Influenza H5N1

PubMed Central

Sonnberg, Stephanie; Webby, Richard J.; Webster, Robert G.

2013-01-01

The ecology of highly pathogenic avian influenza (HPAI) H5N1 has significantly changed from sporadic outbreaks in terrestrial poultry to persistent circulation in terrestrial and aquatic poultry and potentially in wild waterfowl. A novel genotype of HPAI H5N1 arose in 1996 in southern China and through ongoing mutation, reassortment, and natural selection, has diverged into distinct lineages and expanded into multiple reservoir hosts. The evolution of Goose/Guangdong-lineage highly pathogenic H5N1 viruses is ongoing: while stable interactions exist with some reservoir hosts, these viruses are continuing to evolve and adapt to others, and pose an un-calculable risk to sporadic hosts, including humans. PMID:23735535

The Asian house shrew Suncus murinus as a reservoir and source of human outbreaks of plague in Madagascar

PubMed Central

Rajerison, Minoarisoa; Telfer, Sandra; Savin, Cyril; Carniel, Elisabeth; Duplantier, Jean-Marc

2017-01-01

Identifying key reservoirs for zoonoses is crucial for understanding variation in incidence. Plague re-emerged in Mahajanga, Madagascar in the 1990s but there has been no confirmed case since 1999. Here we combine ecological and genetic data, from during and after the epidemics, with experimental infections to examine the role of the shrew Suncus murinus in the plague epidemiological cycle. The predominance of S. murinus captures during the epidemics, their carriage of the flea vector and their infection with Yersinia pestis suggest they played an important role in the maintenance and transmission of plague. S. murinus exhibit a high but variable resistance to experimental Y. pestis infections, providing evidence of its ability to act as a maintenance host. Genetic analyses of the strains isolated from various hosts were consistent with two partially-linked transmission cycles, with plague persisting within the S. murinus population, occasionally spilling over into the rat and human populations. The recent isolation from a rat in Mahajanga of a Y. pestis strain genetically close to shrew strains obtained during the epidemics reinforces this hypothesis and suggests circulation of plague continues. The observed decline in S. murinus and Xenopsylla cheopis since the epidemics appears to have decreased the frequency of spillover events to the more susceptible rats, which act as a source of infection for humans. Although this may explain the lack of confirmed human cases in recent years, the current circulation of plague within the city highlights the continuing health threat. PMID:29155827

HoBi-like virus challenge of pregnant cows that had previously given birth to calves persistently infected with bovine viral diarrhea virus

USDA-ARS?s Scientific Manuscript database

The ability of bovine viral diarrhea viruses (BVDV) to establish persistent infection (PI) following fetal infection is central to keeping these viruses circulating. Similarly, an emerging species of pestivirus, HoBi-like viruses, is also able to establish PIs. Dams that are not PI, but carrying PI ...

[Control of poliomyelitis and enterovirus infection in several areas of Russian Federation].

PubMed

Romanenkova, N I; Bichurina, M A; Rosaeva, N R

2011-01-01

Control of poliovirus circulation by study of material from patients with acute flaccid paralysis and contact individuals, from children of risk groups; molecular characteristics of isolated polioviruses; monitoring of circulation of polioviruses and nonpoliomyelitis enteroviruses in population and the environment. Isolation and study of polioviruses and nonpoliomyelitis enteroviruses from various sources was performed in accordance with WHO recommendations. Prolonged persistence and circulation of vaccine related strains of polioviruses in children is demonstrated. Enterovirus serotypes that circulate in the population and the environment more frequently are determined. CONCLUSION. Long term control of poliomyelitis and acute flaccid paralysis in combination with additional control variants in children from risk groups and objects of the environment allowed to obtain valuable data on poliovirus and nonpoliomyelitis enteroviruses circulation for the Program of eradication of poliomyelitis.

Sex differences in visuospatial abilities persist during induced hypogonadism

PubMed Central

Guerrieri, Gioia M.; Wakim, Paul G.; Keenan, P.A.; Schenkel, Linda A; Berlin, Kate; Gibson, Carolyn J.; Rubinow, David R.; Schmidt, Peter J.

2016-01-01

Background Despite well-established sex differences in the performance on tests of several cognitive domains (e.g., visuospatial ability), few studies in humans have evaluated if these sex differences are evident both in the presence of circulating sex hormones and during sex steroid hormonal suppression. Sex differences identified in the relative absence of circulating levels of estradiol and testosterone suggest that differences in brain structure or function exist independent of current hormonal environment and are more likely a reflection of differing developmental exposures and/or genetic substrates. Objective To evaluate cognitive performance in healthy eugonadal men and women before and again during GnRH agonist-induced hypogonadism. Methods Men (n = 16) and women (n = 15) without medical or psychiatric illness were matched for IQ. Cognitive tests were performed at baseline (when eugonadal) and after 68 weeks of GnRH agonist-induced gonadal suppression. The test batteries included measures of verbal and spatial memory, spatial ability, verbal fluency, motor speed/dexterity, and attention/concentration. Data were analyzed using repeated-measures models. Results During both eugonadism and hypogonadism, men performed significantly better than women on several measures of visuospatial performance including mental rotation, line orientation, Money Road Map, Porteus maze, and complex figure drawing. Although some test performances showed an effect of hormone treatment, the majority of these differences reflected an improved performance during hypogonadism compared with baseline (and probably reflected practice effects). Conclusion The well-documented male advantage in visuospatial performance, which we observed during eugonadal conditions, was maintained in the context of short-term suppression of gonadal function in both men and women. These findings suggest that, in humans, sex differences in visuospatial performance are not merely dependent on differences in the current circulating sex steroid environment. Thus sex differences in visuospatial performance in adulthood could reflect early developmental effects of sex steroid exposure or other environmental exposures differing across the sexes as our data confirm that these differences are independent of circulating estradiol or testosterone levels in men and women. PMID:26719236

Sex differences in visuospatial abilities persist during induced hypogonadism.

PubMed

Guerrieri, Gioia M; Wakim, Paul G; Keenan, P A; Schenkel, Linda A; Berlin, Kate; Gibson, Carolyn J; Rubinow, David R; Schmidt, Peter J

2016-01-29

Despite well-established sex differences in the performance on tests of several cognitive domains (e.g., visuospatial ability), few studies in humans have evaluated if these sex differences are evident both in the presence of circulating sex hormones and during sex steroid hormonal suppression. Sex differences identified in the relative absence of circulating levels of estradiol and testosterone suggest that differences in brain structure or function exist independent of current hormonal environment and are more likely a reflection of differing developmental exposures and/or genetic substrates. To evaluate cognitive performance in healthy eugonadal men and women before and again during GnRH agonist-induced hypogonadism. Men (n=16) and women (n=15) without medical or psychiatric illness were matched for IQ. Cognitive tests were performed at baseline (when eugonadal) and after 6-8 weeks of GnRH agonist-induced gonadal suppression. The test batteries included measures of verbal and spatial memory, spatial ability, verbal fluency, motor speed/dexterity, and attention/concentration. Data were analyzed using repeated-measures models. During both eugonadism and hypogonadism, men performed significantly better than women on several measures of visuospatial performance including mental rotation, line orientation, Money Road Map, Porteus maze, and complex figure drawing. Although some test performances showed an effect of hormone treatment, the majority of these differences reflected an improved performance during hypogonadism compared with baseline (and probably reflected practice effects). The well-documented male advantage in visuospatial performance, which we observed during eugonadal conditions, was maintained in the context of short-term suppression of gonadal function in both men and women. These findings suggest that, in humans, sex differences in visuospatial performance are not merely dependent on differences in the current circulating sex steroid environment. Thus sex differences in visuospatial performance in adulthood could reflect early developmental effects of sex steroid exposure or other environmental exposures differing across the sexes as our data confirm that these differences are independent of circulating estradiol or testosterone levels in men and women. Published by Elsevier Ltd.

A new threat to human reproduction system posed by Zika virus (ZIKV): From clinical investigations to experimental studies.

PubMed

Li, Xiangdong; Ma, Wenqiang; Wong, Gary; Ma, Shuoqian; Li, Shihua; Bi, Yuhai; Gao, George F

2017-09-08

Zika virus (ZIKV) was first isolated in 1947 from a rhesus monkey in the Zika forest of Uganda. ZIKV has since been silently circulating in a number of equatorial countries for over 50 years. The largest outbreak in humans occurred in Brazil in 2015-2016. Unlike its flavivirus relatives, sexual and post-transfusion transmissions of ZIKV have been reported. In addition, fetal infection can result in microcephaly and congenital Zikv syndrome has been reported in neonates. Moreover, ZIKV RNA can persist for at least 6 months in semen and 11 weeks in vaginal secretions after the infection, suggesting potential tropism for the male and female genital tracts. Accordingly, it is important to determine whether genital ZIKV infection could have deleterious effects on the male and female reproductive systems. Copyright © 2017. Published by Elsevier B.V.

Associations between blood persistent organic pollutants and 25-hydroxyvitamin D3 in pregnancy.

PubMed

Morales, Eva; Gascon, Mireia; Martinez, David; Casas, Maribel; Ballester, Ferran; Rodríguez-Bernal, Clara L; Ibarluzea, Jesus; Marina, Loreto Santa; Espada, Mercedes; Goñi, Fernando; Vizcaino, Esther; Grimalt, Joan O; Sunyer, Jordi

2013-07-01

Persistent organic pollutants (POPs) are suggested to contribute to lower vitamin D levels; however, studies in humans are scarce and have never focused on pregnancy, a susceptibility period for vitamin D deficiency. We investigated whether serum levels of POPs were associated with circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration in pregnancy. Cross-sectional associations of serum concentrations of eight POPs with plasma 25(OH)D3 concentration were analyzed in 2031 pregnant women participating in the Spanish population-based cohort INfancia y Medio Ambiente (INMA) Project. Serum concentrations of POPs were measured by gas chromatography and plasma 25(OH)D3 concentration was measured by high-performance liquid chromatography in pregnancy (mean 13.3±1.5weeks of gestation). Multivariable regression models were performed to assess the relationship between blood concentrations of POPs and 25(OH)D3. An inverse linear relationship was found between serum concentration of PCB180 and circulating 25(OH)D3. Multivariate linear regression models showed higher PCB180 levels to be associated with lower 25(OH)D3 concentration: quartile Q4 vs. quartile Q1, coefficient=-1.59, 95% CI -3.27, 0.08, p trend=0.060. A non-monotonic inverse relationship was found between the sum of predominant PCB congeners (PCB 180, 153 and 138) and 25(OH)D3 concentration: coefficient (95% CI) for quartile Q2 vs. Q1 [-0.50 (-1.94, 0.94)], quartile Q3 vs. Q1 [-1.56 (-3.11, -0.02)] and quartile Q4 vs. Q1 [-1.21 (-2.80, 0.38)], p trend=0.081. No significant associations were found between circulating 25(OH)D3 and serum levels of p,p'-DDE, p,p'-DDT, HCB, and ß-HCH. Our results suggest that the background exposure to PCBs may result in lower 25(OH)D3 concentration in pregnant women. Copyright © 2013 Elsevier Ltd. All rights reserved.

The use of stellite scatterometer winds to drive a primitive equation model of the Indian Ocean: The impact of bandlike sampling

NASA Technical Reports Server (NTRS)

Barnier, Bernard; Capella, Jorge; O'Brien, James J.

1994-01-01

The aim of this study is to evaluate the impact of the bandlike sampling of spaceborne scatterometers on the ability of scatterometer winds to successfully force the mean flow and seasonal cycle of an ocean model in the context of equatorial and tropical dynamics. The equatorial ocean is simulated with a four-layer, primitive equation, reduced gravity model of the Indian Ocean. The variable wind stress used in this study is derived from one year (1988) of 6-hour analyses of the 10-m wind vector over the Indian Ocean performed at the European Centre for Medium-Range Weather Forecasts (ECMWF). It is applied as a forcing at every grid point of the model to drive a reference circulation. Scatterometer winds are simulated from ECMWF winds, using the nominal configurations and orbital parameters of the European Remote Sensing 1 (ERS-1) and NASA Scatterometer (NSCAT) missions. The model is forced in real time under swaths with the raw scatterometer winds of ERS-1 and NSCAT, with a persistence condition (i.e., the wind is kept constsnt until the next passage of the satellite provides a new value). The circulation obtained for each of the scatterometer experiments is compared with the reference circulation. The seasonal circulation of the Indian Ocean with NSCAT winds is very similar to the reference. The perturbations introduced by the bandlike sampling and the persistance condition have an impact similar to that of a small uncorrelated noise added to the reference forcing. The persistence condition for ERS-1 does not give results which are as good as those obtained for NSCAT.

The effect of lipid monolayer in-plane rigidity on in vivo microbubble circulation persistence

PubMed Central

Garg, Sumit; Thomas, Alex A.; Borden, Mark A.

2013-01-01

The goal of this study was to increase in vivo microbubble circulation persistence for applications in medical imaging and targeted drug delivery. Our approach was to investigate the effect of lipid monolayer in-plane rigidity to reduce the rate of microbubble dissolution, while holding constant the microbubble size, concentration and surface architecture. We first estimated the impact of acyl chain length of the main diacyl phosphatidyl-choline (PC) lipid and inter-lipid distance on the cohesive surface energy and, based on these results, we hypothesized that microbubble stability and in vivo ultrasound contrast persistence would increase monotonically with increasing acyl chain length. We therefore measured microbubble in vitro stability to dilution with and without ultrasound exposure, as well as in vivo ultrasound contrast persistence. All measurements showed a sharp rise in stability between DPPC (C16:0) and DSPC (C18:0), which correlates to the wrinkling transition, which signals the onset of significant surface shear and gas permeation resistance, observed in prior single-bubble dissolution studies. Further evidence for the effect of the wrinkling transition came from an in vitro and in vivo stability comparison of microbubbles coated with pure DPPC with those of lung surfactant extract. Microbubble stability against dilution without ultrasound and in vivo ultrasound contrast persistence showed a monotonic increase with acyl chain length from DSPC to DBPC (C22:0). However, we also observed that stability dropped precipitously for all measurements on further increasing lipid acyl chain length from DBPC to DLiPC (C24:0). This result suggests that hydrophobic mismatch between the main PC lipid and the lipopolymer emulsifier, DSPE-PEG5000, may drive a less stable surface microstructure. Overall, these results support our general hypothesis of the role of in-plane rigidity for increasing the lifetime of microbubble circulation. PMID:23787108

Circulating anti-Müllerian hormone (AMH) associates with the maturity of boys' drawings: Does AMH slow cognitive development in males?

PubMed

Morgan, Kirstie; Ruffman, Ted; Bilkey, David K; McLennan, Ian S

2017-09-01

High levels of circulating anti-Müllerian hormone are unique to developing males, but the function of anti-Müllerian hormone in boys is unknown. In mice, anti-Müllerian hormone contributes to the male biases in the brain, but its receptors are present throughout non-sexually dimorphic portions of the brain. In humans, the speed of maturation is the most overt difference between girls and boys. We postulate that this is because anti-Müllerian hormone slows the maturation of the male human brain. One hundred and fourty three 5-year or 6-year-old boys and 38 age-matched girls drew a person and donated a blood sample. The children's drawings were blind-scored to generate a maturity index. The level of anti-Müllerian hormone and the other Sertoli cell hormone, inhibin B, were measured by ELISA. The relationship between the children's age, hormones and maturity index were examined by linear regression analysis. The girls drew more complex and realistic person than the boys (32%, p = 0.001), with their drawings also being larger (39%, p = 0.037) and more coloured-in (235%, p = 0.0005). The maturity index in boys correlated with age (+r = 0.43, p < 0.0005) and anti-Müllerian hormone level (-r = -0.29, p < 0.0005). The association between maturity index and anti-Müllerian hormone level persisted when corrected for age and for inhibin B (r = -0.24, p = 0.0005). The calculated effect of the median level of anti-Müllerian hormone (1 nM) was equal to 0.81 months of development. The size and colouring of the drawings did not correlate with the boys' age, anti-Müllerian hormone or inhibin B. This exploratory study provides the first indicative evidence that circulating anti-Müllerian hormone may influence the development of the human brain.

NASA A-Train and Terra Observations of the 2010 Russian Wildfires

NASA Technical Reports Server (NTRS)

Witte, J. C.; Douglass, A. R.; DaSilva, A.; Torres, O.; Levy, R.; Duncan, B. N.

2011-01-01

Wildfires raged throughout western Russia and parts of Eastern Europe during a persistent heat wave in the summer of 2010. Anomalously high surface temperatures (35 - 41 C) and low relative humidity (9 - 25 %) from mid- June to mid-August 2010 shown by analysis of radiosonde data from multiple sites in western Russia were ideal conditions for the wildfires to thrive. Measurements of outgoing longwave radiation (OLR) from the Atmospheric Infrared Sounder (AIRS) over western Russian indicate persistent subsidence during the heat wave. Daily three-day back-trajectories initiated over Moscow reveal a persistent anticyclonic circulation for 18 days in August, coincident with the most intense period of fire activity observed by Moderate Resolution Imaging Spectroradiometer (MODIS). This unfortunate meteorological coincidence allowed transport of polluted air from the region of intense fires to Moscow and the surrounding area. We demonstrate that the 2010 Russian wildfires are unique in the record of observations obtained by remote-sensing instruments on-board NASA satellites: Aura and Aqua (part of the A-Train Constellation) and Terra. Analysis of the distribution of MODIS fire products and aerosol optical thickness (AOT), UV aerosol index (AI) and single-scattering albedo (SSA) from Aura's Ozone Monitoring Instrument (OMI), and total column carbon monoxide (CO) from Aqua s Atmospheric Infrared Sounder (AIRS) show that the region in the center of western Russia surrounding Moscow (52-58 deg N, 33 -43 deg E) is most severely impacted by wildfire emissions. Over this area, AIRS CO, OMI AI, and MODIS AOT are significantly enhanced relative to the historical satellite record during the first 18 days in August when the anti-cyclonic circulation persisted. By mid-August, the anti-cyclonic circulation was replaced with westerly transport over Moscow and vicinity. The heat wave

An Observational Case Study of Persistent Fog and Comparison with an Ensemble Forecast Model

NASA Astrophysics Data System (ADS)

Price, Jeremy; Porson, Aurore; Lock, Adrian

2015-05-01

We present a study of a persistent case of fog and use the observations to evaluate the UK Met Office ensemble model. The fog appeared to form initially in association with small patches of low-level stratus and spread rapidly across southern England during 11 December 2012, persisting for 24 h. The low visibility and occurrence of fog associated with the event was poorly forecast. Observations show that the surprisingly rapid spreading of the layer was due to a circulation at the fog edge, whereby cold cloudy air subsided into and mixed with warmer adjacent clear air. The resulting air was saturated, and hence the fog layer grew rapidly outwards from its edge. Measurements of fog-droplet deposition made overnight show that an average of 12 g m h was deposited but that the liquid water content remained almost constant, indicating that further liquid was condensing at a similar rate to the deposition, most likely due to the slow cooling. The circulation at the fog edge was also present during its dissipation, by which time the fog top had lowered by 150 m. During this period the continuing circulation at the fog edge, and increasing wind shear at fog top, acted to dissipate the fog by creating mixing with, by then, the drier adjacent and overlying air. Comparisons with a new, high resolution Met Office ensemble model show that this type of case remains challenging to simulate. Most ensemble members successfully simulated the formation and persistence of low stratus cloud in the region, but produced too much cloud initially overnight, which created a warm bias. During the daytime, ensemble predictions that had produced fog lifted it into low stratus, whilst in reality the fog remained present all day. Various aspects of the model performance are discussed further.

Transmission or Within-Host Dynamics Driving Pulses of Zoonotic Viruses in Reservoir–Host Populations

PubMed Central

Plowright, Raina K.; Peel, Alison J.; Streicker, Daniel G.; Gilbert, Amy T.; McCallum, Hamish; Wood, James; Baker, Michelle L.; Restif, Olivier

2016-01-01

Progress in combatting zoonoses that emerge from wildlife is often constrained by limited knowledge of the biology of pathogens within reservoir hosts. We focus on the host–pathogen dynamics of four emerging viruses associated with bats: Hendra, Nipah, Ebola, and Marburg viruses. Spillover of bat infections to humans and domestic animals often coincides with pulses of viral excretion within bat populations, but the mechanisms driving such pulses are unclear. Three hypotheses dominate current research on these emerging bat infections. First, pulses of viral excretion could reflect seasonal epidemic cycles driven by natural variations in population densities and contact rates among hosts. If lifelong immunity follows recovery, viruses may disappear locally but persist globally through migration; in either case, new outbreaks occur once births replenish the susceptible pool. Second, epidemic cycles could be the result of waning immunity within bats, allowing local circulation of viruses through oscillating herd immunity. Third, pulses could be generated by episodic shedding from persistently infected bats through a combination of physiological and ecological factors. The three scenarios can yield similar patterns in epidemiological surveys, but strategies to predict or manage spillover risk resulting from each scenario will be different. We outline an agenda for research on viruses emerging from bats that would allow for differentiation among the scenarios and inform development of evidence-based interventions to limit threats to human and animal health. These concepts and methods are applicable to a wide range of pathogens that affect humans, domestic animals, and wildlife. PMID:27489944

Genesis and genetic constellations of swine influenza viruses in Thailand.

PubMed

Poonsuk, Sukontip; Sangthong, Pradit; Petcharat, Nantawan; Lekcharoensuk, Porntippa

2013-12-27

Swine influenza virus (SIV) is one of the most important zoonotic agents and the origin of the most recent pandemic virus. Asia is considered to be the epicenter for genetic exchanging of influenza A viruses and Southeast Asia including Thailand serves as a reservoir to maintain the persistence of the viruses for seeding other regions. Therefore, searching for new reassortants in this area has been routinely required. Although SIVs in Thailand have been characterized, collective information regarding their genetic evolution and gene constellations is limited. In this study, whole genomes of 30 SIVs isolated during clinical target surveillance plus all available sequences of past and currently circulating Thai SIVs were genetically characterized based on their evolutionary relationships. All genetic pools of Thai SIVs are comprised of four lineages including classical swine (CS), Eurasian swine (EAs), Triple reassortants (TRIG) and Seasonal human (Shs). Out of 84 isolates, nine H1N1, six H3N2 and one H1N2 strains were identified. Gene constellations of SIVs in Thailand are highly complex resulting from multiple reassortments among concurrently circulating SIVs and temporally introduced foreign genes. Most strains contain gene segments from both EAs and CS lineages and appeared transiently. TRIG lineage has been recently introduced into Thai SIV gene pools. The existence of EAs and TRIG lineages in this region may increase rates of genetic exchange and diversity while Southeast Asia is a persistent reservoir for influenza A viruses. Continual monitoring of SIV evolution in this region is crucial in searching for the next potential pandemic viruses. Copyright © 2013 Elsevier B.V. All rights reserved.

North Atlantic Deep Water formation inhibits high Arctic contamination by continental perfluorooctane sulfonate discharges

NASA Astrophysics Data System (ADS)

Zhang, Xianming; Zhang, Yanxu; Dassuncao, Clifton; Lohmann, Rainer; Sunderland, Elsie M.

2017-08-01

Perfluorooctane sulfonate (PFOS) is an aliphatic fluorinated compound with eight carbon atoms that is extremely persistent in the environment and can adversely affect human and ecological health. The stability, low reactivity, and high water solubility of PFOS combined with the North American phaseout in production around the year 2000 make it a potentially useful new tracer for ocean circulation. Here we characterize processes affecting the lifetime and accumulation of PFOS in the North Atlantic Ocean and transport to sensitive Arctic regions by developing a 3-D simulation within the MITgcm. The model captures variability in measurements across biogeographical provinces (R2 = 0.90, p = 0.01). In 2015, the North Atlantic PFOS reservoir was equivalent to 60% of cumulative inputs from the North American and European continents (1400 Mg). Cumulative inputs to the Arctic accounted for 30% of continental discharges, while the remaining 10% was transported to the tropical Atlantic and other regions. PFOS concentrations declined rapidly after 2002 in the surface mixed layer (half-life: 1-2 years) but are still increasing below 1000 m depth. During peak production years (1980-2000), plumes of PFOS-enriched seawater were transported to the sub-Arctic in energetic surface ocean currents. However, Atlantic Meridional Overturning Circulation (AMOC) and deep ocean transport returned a substantial fraction of this northward transport (20%, 530 Mg) to southern latitudes and reduced cumulative inputs to the Arctic (730 Mg) by 70%. Weakened AMOC due to climate change is thus likely to increase the magnitude of persistent bioaccumulative pollutants entering the Arctic Ocean.

Butterflies, Black swans and Dragon kings: How to use the Dynamical Systems Theory to build a "zoology" of mid-latitude circulation atmospheric extremes?

NASA Astrophysics Data System (ADS)

Faranda, D.; Yiou, P.; Alvarez-Castro, M. C. M.

2015-12-01

A combination of dynamical systems and statistical techniques allows for a robust assessment of the dynamical properties of the mid-latitude atmospheric circulation. Extremes at different spatial and time scales are not only associated to exceptionally intense weather structures (e.g. extra-tropical cyclones) but also to rapid changes of circulation regimes (thunderstorms, supercells) or the extreme persistence of weather structure (heat waves, cold spells). We will show how the dynamical systems theory of recurrence combined to the extreme value theory can take into account the spatial and temporal dependence structure of the mid-latitude circulation structures and provide information on the statistics of extreme events.

Molecular epidemiology of oyster-related human noroviruses and their global genetic diversity and temporal-geographical distribution from 1983 to 2014.

PubMed

Yu, Yongxin; Cai, Hui; Hu, Linghao; Lei, Rongwei; Pan, Yingjie; Yan, Shuling; Wang, Yongjie

2015-11-01

Noroviruses (NoVs) are a leading cause of epidemic and sporadic cases of acute gastroenteritis worldwide. Oysters are well recognized as the main vectors of environmentally transmitted NoVs, and disease outbreaks linked to oyster consumption have been commonly observed. Here, to quantify the genetic diversity, temporal distribution, and circulation of oyster-related NoVs on a global scale, 1,077 oyster-related NoV sequences deposited from 1983 to 2014 were downloaded from both NCBI GenBank and the NoroNet outbreak database and were then screened for quality control. A total of 665 sequences with reliable information were obtained and were subsequently subjected to genotyping and phylogenetic analyses. The results indicated that the majority of oyster-related NoV sequences were obtained from coastal countries and regions and that the numbers of sequences in these regions were unevenly distributed. Moreover, >80% of human NoV genotypes were detected in oyster samples or oyster-related outbreaks. A higher proportion of genogroup I (GI) (34%) was observed for oyster-related sequences than for non-oyster-related outbreaks, where GII strains dominated with an overwhelming majority of >90%, indicating that the prevalences of GI and GII are different in humans and oysters. In addition, a related convergence of the circulation trend was found between oyster-related NoV sequences and human pandemic outbreaks. This suggests that oysters not only act as a vector of NoV through environmental transmission but also serve as an important reservoir of human NoVs. These results highlight the importance of oysters in the persistence and transmission of human NoVs in the environment and have important implications for the surveillance of human NoVs in oyster samples. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Vascular Endothelial Growth Factor (VEGF) mRNA Isoforms are Altered in Bovine Granulosa Cells (GC) by Circulating Progestin Concentrations (P4) and May Indicate Follicle Status and Oocyte Competence

USDA-ARS?s Scientific Manuscript database

Previously, Melengestrol Acetate (MGA) fed for 14 d (0.5mg/cow/d; < 1 ng/ml P4) resulted in persistent follicles with increased size, decreased number of GC/follicular fluid (FF) volume, and less fertile oocytes. An experiment was conducted to determine effects of circulating P4 on amount of mRNA fo...

Electrocardiographic findings in Mexican chagasic subjects living in high and low endemic regions of Trypanosoma cruzi infection.

PubMed

Sosa-Jurado, Francisca; Mazariego-Aranda, Miguel; Hernández-Becerril, Nidia; Garza- Murillo, Verónica; Cárdenas, Manuel; Reyes, Pedro A; Hirayama, Kenji; Monteón, Victor M

2003-07-01

In México the first human chronic chagasic case was recognized in 1940. In spite of an increasing number of cases detected since that time, Chagas disease in México has been poorly documented. In the present work we studied 617 volunteers subjects living in high and low endemic regions of Trypanosoma cruzi infection with seroprevalence of 22% and 4% respectively. Hemoculture performed in those seropositive subjects failed to demonstrate circulating parasites, however polymerase chain reaction identified up to 60% of them as positives. A higher level of anti-T. cruzi antibodies was observed in seropositive residents in high endemic region, in spite of similar parasite persistence (p < 0.05). On standard 12 leads electrocardiogram (ECG) 20% to 22% seropositive individuals from either region showed right bundle branch block or ventricular extrasystoles which were more prevalent in seropositive than in seronegative individuals (p < 0.05). In conclusion, the frequency or type of ECG abnormality was influenced by serologic status but not by endemicity or parasite persistence. Furthermore, Mexican indeterminate patients have a similar ECG pattern to those reported in South America.

Genetic analysis and characterization of wild poliovirus type 1 during sustained transmission in a population with >95% vaccine coverage, Israel 2013.

PubMed

Shulman, Lester M; Martin, Javier; Sofer, Danit; Burns, Cara C; Manor, Yossi; Hindiyeh, Musa; Gavrilin, Eugene; Wilton, Thomas; Moran-Gilad, Jacob; Gamzo, Ronni; Mendelson, Ella; Grotto, Itamar

2015-04-01

Israel has >95% polio vaccine coverage with the last 9 birth cohorts immunized exclusively with inactivated polio vaccine (IPV). Using acute flaccid paralysis and routine, monthly countrywide environmental surveillance, no wild poliovirus circulation was detected between 1989 and February 2013, after which wild type 1 polioviruses South Asia genotype (WPV1-SOAS) have persistently circulated in southern Israel and intermittently in other areas without any paralytic cases as determined by intensified surveillance of environmental and human samples. We aimed to characterize antigenic and neurovirulence properties of WPV1-SOAS silently circulating in a highly vaccinated population. WPV1-SOAS capsid genes from environmental and stool surveillance isolates were sequenced, their neurovirulence was determined using transgenic mouse expressing the human poliovirus receptor (Tg21-PVR) mice, and their antigenicity was characterized by in vitro neutralization using human sera, epitope-specific monoclonal murine anti-oral poliovirus vaccine (OPV) antibodies, and sera from IPV-immunized rats and mice. WPV1 amino acid sequences in neutralizing epitopes varied from Sabin 1 and Mahoney, with little variation among WPV1 isolates. Neutralization by monoclonal antibodies against 3 of 4 OPV epitopes was lost. Three-fold lower geometric mean titers (Z = -4.018; P < .001, Wilcoxon signed-rank test) against WPV1 than against Mahoney in human serum correlated with 4- to 6-fold lower neutralization titers in serum from IPV-immunized rats and mice. WPV1-SOAS isolates were neurovirulent (50% intramuscular paralytic dose in Tg21-PVR mice: log10(7.0)). IPV-immunized mice were protected against WPV1-induced paralysis. Phenotypic and antigenic profile changes of WPV1-SOAS may have contributed to the intense silent transmission, whereas the reduced neurovirulence may have contributed to the absence of paralytic cases in the background of high population immunity. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Stochastic Model to Study Rift Valley Fever Persistence with Different Seasonal Patterns of Vector Abundance: New Insights on the Endemicity in the Tropical Island of Mayotte

PubMed Central

Dommergues, Laure; Zumbo, Betty; Cardinale, Eric

2015-01-01

Rift Valley fever (RVF) is a zoonotic vector-borne disease causing abortion storms in cattle and human epidemics in Africa. Our aim was to evaluate RVF persistence in a seasonal and isolated population and to apply it to Mayotte Island (Indian Ocean), where the virus was still silently circulating four years after its last known introduction in 2007. We proposed a stochastic model to estimate RVF persistence over several years and under four seasonal patterns of vector abundance. Firstly, the model predicted a wide range of virus spread patterns, from obligate persistence in a constant or tropical environment (without needing vertical transmission or reintroduction) to frequent extinctions in a drier climate. We then identified for each scenario of seasonality the parameters that most influenced prediction variations. Persistence was sensitive to vector lifespan and biting rate in a tropical climate, and to host viraemia duration and vector lifespan in a drier climate. The first epizootic peak was primarily sensitive to viraemia duration and thus likely to be controlled by vaccination, whereas subsequent peaks were sensitive to vector lifespan and biting rate in a tropical climate, and to host birth rate and viraemia duration in arid climates. Finally, we parameterized the model according to Mayotte known environment. Mosquito captures estimated the abundance of eight potential RVF vectors. Review of RVF competence studies on these species allowed adjusting transmission probabilities per bite. Ruminant serological data since 2004 and three new cross-sectional seroprevalence studies are presented. Transmission rates had to be divided by more than five to best fit observed data. Five years after introduction, RVF persisted in more than 10% of the simulations, even under this scenario of low transmission. Hence, active surveillance must be maintained to better understand the risk related to RVF persistence and to prevent new introductions. PMID:26147799

Heterosubtypic anti-avian H5N1 influenza antibodies in intravenous immunoglobulins from globally separate populations protect against H5N1 infection in cell culture

PubMed Central

Sullivan, John S; Selleck, Paul W; Downton, Teena; Boehm, Ingrid; Axell, Anna-Maree; Ayob, Yasmin; Kapitza, Natalie M; Dyer, Wayne; Fitzgerald, Anna; Walsh, Bradley; Lynch, Garry W

2009-01-01

With antigenically novel epidemic and pandemic influenza strains persistently on the horizon it is of fundamental importance that we understand whether heterosubtypic antibodies gained from exposures to circulating human influenzas exist and can protect against emerging novel strains. Our studies of IVIG obtained from an infection-naive population (Australian) enabled us to reveal heterosubtypic influenza antibodies that cross react with H5N1. We now expand those findings for an Australian donor population to include IVIG formulations from a variety of northern hemisphere populations. Examination of IVIGs from European and South East-Asian (Malaysian) blood donor populations further reveal heterosubtypic antibodies to H5N1 in humans from different global regions. Importantly these protect against highly pathogenic avian H5N1 infection in vitro, albeit at low titres of inhibition. Although there were qualitative and quantitative differences in binding and protection between globally different formulations, the heterosubtypic antibody activities for the respective IVIGs were in general quite similar. Of particular note because of the relative geographic proximity to the epicentre of H5N1 and the majority of human infections, was the similarity in the antibody binding responses between IVIGs from the Malayan peninsula, Europe and Australia. These findings highlight the value of employing IVIGs for the study of herd immunity, and particularly heterosubtypic antibody responses to viral antigens such as those conserved between circulating human influenzas and emerging influenza strains such as H5N1. They also open a window into a somewhat ill defined arena of antibody immunity, namely heterosubtypic immunity. PMID:20076794

Stochastic simulation of human pulmonary blood flow and transit time frequency distribution based on anatomic and elasticity data.

PubMed

Huang, Wei; Shi, Jun; Yen, R T

2012-12-01

The objective of our study was to develop a computing program for computing the transit time frequency distributions of red blood cell in human pulmonary circulation, based on our anatomic and elasticity data of blood vessels in human lung. A stochastic simulation model was introduced to simulate blood flow in human pulmonary circulation. In the stochastic simulation model, the connectivity data of pulmonary blood vessels in human lung was converted into a probability matrix. Based on this model, the transit time of red blood cell in human pulmonary circulation and the output blood pressure were studied. Additionally, the stochastic simulation model can be used to predict the changes of blood flow in human pulmonary circulation with the advantage of the lower computing cost and the higher flexibility. In conclusion, a stochastic simulation approach was introduced to simulate the blood flow in the hierarchical structure of a pulmonary circulation system, and to calculate the transit time distributions and the blood pressure outputs.

Processes and mechanisms of persistent extreme precipitation events in East China

NASA Astrophysics Data System (ADS)

Zhai, Panmao; Chen, Yang

2014-11-01

This study mainly presents recent progresses on persistent extreme precipitation events (PEPEs) in East China. A definition focusing both persistence and extremity of daily precipitation is firstly proposed. An identification method for quasi-stationary regional PEPEs is then designed. By utilizing the identified PEPEs in East China, typical circulation configurations from the lower to the upper troposphere are confirmed, followed by investigations of synoptic precursors for key components with lead time of 1-2 weeks. Two characteristic circulation patterns responsible for PEPEs in East China are identified: a double blocking high type and a single blocking high type. They may account for occurrence of nearly 80% PEPEs during last 60 years. For double blocking high type, about two weeks prior to PEPEs, two blockings developed and progressed towards the Ural Mountains and the Sea of Okhotsk, respectively. A northwestward progressive anomalous anticyclone conveying abundant moisture and eastward-extended South Asia High favoring divergence can be detected about one week in advance. A dominant summertime teleconnection over East Asia, East Asia/ Pacific (EAP) pattern, is deemed as another typical regime inducing PEPEs in the East China. Key elements of the EAP pattern initiated westward movement since one week prior to PEPEs. Eastward energy dispersion and poleward energy dispersion contributed to early development and subsequent maintenance of this teleconnection pattern, respectively. These typical circulation patterns and significant precursors may offer local forecasters some useful clues in identifying and predicting such high-impact precipitation events about 1-2 weeks in advance.

Persistence of genetic variants of the arctic fox strain of Rabies virus in southern Ontario.

PubMed

Nadin-Davis, Susan A; Muldoon, Frances; Wandeler, Alexander I

2006-01-01

Genetic-variant analysis of rabies viruses provides the most sensitive epidemiologic tool for following the spread and persistence of these viruses in their wildlife hosts. Since its introduction by a southern epizootic movement that began in the far north, the arctic fox (AFX) strain of Rabies virus has been enzootic in Ontario for almost 50 y. Prior genetic studies identified 4 principal genetic variants (ONT.T1 to ONT.T4) that were localized to different regions of the province; furthermore, these viruses could be distinguished from the variant circulating in northern regions of Quebec, Newfoundland, and arctic zones, ARC.T5. Despite an intensive provincial control program undertaken over the last decade that involved aerial distribution of baits laden with rabies vaccine to combat fox rabies throughout the enzootic zone of Ontario, pockets of rabies activity persist. Re-evaluation of the genetic characteristics of the viral variants circulating in these areas of persistence has been undertaken. These data demonstrate that the recent outbreaks are, with 1 exception, due to persistence of the regional variant first identified in the area in the early 1990s. In contrast, the disease in the Georgian Bay area is a consequence of the incursion of a variant previously found further south. An outbreak that occurred in northern Ontario north and west of North Bay and in the neighboring border areas of Quebec in 2000-2001 was due to renewed incursion of the ARC.T5 variant from more northerly areas.

Application of the solid phase C1q and Raji cell radioimmune assays for the detection of circulating immune complexes in glomerulonephritis.

PubMed Central

Tung, K S; Woodroffe, A J; Ahlin, T D; Williams, R C; Wilson, C B

1978-01-01

The C1q solid phase and Raji cell radioimmune assays were used to determine the frequency of detectable circulating immune complexes in patients with glomerulonephritis. In this study, 46% of 56 patients with glomerulonephritis had evidence of circulating immune complexes. More important, circulating immune complexes were associated with some, but not other, types of glomerulonephritis. Thus, immune complexes were detected in lupus glomerulonephritis (9/9 patients), rapidly progressive glomerulonephritis (5/6 patients), and acute nephritis (5/6 patients), but not in IgA-IgG glomerulonephritis (0/7 patients), or membranous glomerulonephritis (0/8 patients). The Raji cell radioimmune assay and the C1q solid phase radioimmune assay showed concordance of 79% in the detection of circulating immune complexes. Serial determinations, in general, showed either persistence of a negative or positive result of conversion of positive to negative. PMID:659639

Single-Dose Universal Hepatitis A Immunization in Argentina: Low Viral Circulation and High Persistence of Protective Antibodies Up to 4 Years.

PubMed

Vizzotti, C; González, J; Rearte, A; Urueña, A; Pérez Carrega, M; Calli, R; Gentile, A; Uboldi, A; Ramonet, M; Cañero-Velasco, M; Diosque, M

2015-12-01

Single-dose hepatitis A virus (HAV) vaccination was implemented in all Argentinean children aged 12 months in 2005. Between 2005 and 2011, a dramatic decline was observed in HAV infection rates, fulminant hepatitis, and liver transplantation. This study assessed current viral circulation and estimated protective antibody persistence 4 years after vaccination. Prevalence of prevaccination anti-HAV antibodies in 12-month-old children was evaluated as an indirect estimation of viral circulation (Group A). Seroprevalence was also measured in 5-year-old children who received 1 dose of HAV vaccine at 1 year of age (Group B). Blood samples were tested for immunoglobulin (Ig)G anti-HAV antibodies (seroprotection = ≥10 mIU/mL). All Group A-positive samples were tested for IgM anti-HAV antibodies to identify recent infections. Logistic regression analysis was done to evaluate associations between demographic and socioeconomic variables and seroprotection. Of 433 children from Group A, 29.5% (95% confidence interval [CI], 25.2-33.8) were positive for IgG anti-HAV antibodies with a geometric mean concentration (GMC) of 6.17 mIU/mL (95% CI, 5.33-7.15 mIU/mL); all IgM anti-HAV were negative. From 1139 in Group B, 93% (95% CI, 91.7-94.6) maintained seroprotection with a GMC of 97.96 mIU/mL (95% CI, 89.21-107.57 mIU/mL). Kindergarten attendance was associated with seroprotection in Group B (odds ratio [OR], 2.0; 95% CI, 1.26-3.3). In contrast, high maternal educational level was associated with a lack of seroprotection in this group (OR, .26; 95% CI, .09-.8). Single-dose, universal hepatitis A immunization in infants resulted in low HAV circulation and persistent immunologic protection up to 4 years in Argentina. Variables associated with presence or absence of seroprotection in vaccinated children could be related to differences in hygiene habits in settings with residual viral circulation. © The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Changes in Stratospheric Transport and Mixing During Sudden Stratospheric Warmings

NASA Astrophysics Data System (ADS)

de la Cámara, A.; Abalos, M.; Hitchcock, P.

2018-04-01

The extreme disruptions of the wintertime stratospheric circulation during sudden stratospheric warmings (SSW) have large effects on tracer concentrations through alterations in transport. This study analyzes the changes in residual circulation and isentropic mixing associated with SSWs, by performing composites using reanalysis (European Centre for Medium-Range Weather Forecasts Re-Analysis Interim) and simulations of the Whole Atmosphere Community Climate Model. The advective Brewer-Dobson circulation accelerates around 15 days prior to the wind reversal at 60°N, 10 hPa during the onset of SSWs. Soon afterward, it decelerates, leading to reduced advective transport into the vortex and descent over the pole, which persist for more than 2 months below 30 hPa. The isentropic mixing has a distinct signature in altitude: It is enhanced at the central date of the SSW in the midstratosphere (about 10 hPa or 800 K), and this signal is delayed and more persistent at lower altitudes. It is shown that sufficiently deep SSWs (particularly those related to Polar-night Jet Oscillation events) have a stronger response in the Brewer-Dobson circulation and mixing. In particular, both the polar downwelling and the tropical upwelling are anomalously weak in the lower stratosphere for 90 days after the onset of Polar-night Jet Oscillation events. The redistribution of potential vorticity during the life cycle of SSWs is discussed due to its relevance for the stratospheric circulation. It is shown that the diffusive flux of potential vorticity, calculated in equivalent latitude coordinates, remains anomalously high in the lower stratosphere, a feature that is not seen in more conventional advective eddy fluxes across latitude circles.

Activation of human herpesviruses 6 and 7 in patients with chronic fatigue syndrome.

PubMed

Chapenko, S; Krumina, A; Kozireva, S; Nora, Z; Sultanova, A; Viksna, L; Murovska, M

2006-12-01

Human herpesvirus 6 (HHV-6) and 7 (HHV-7) have been suggested as possible triggering agents for chronic fatigue syndrome (CFS). To determine the possible association of HHV-6 and HHV-7 infections with CFS. The prevalence of latent/persistent and active viral infections by nPCR, characteristic of HHV-6 variants using restriction endonuclease analysis and changes of lymphocyte subsets in peripheral blood by laser flow-cytometry in 17 CFS patients was examined. In addition, 12 patients with unexplained chronic fatigue and 20 blood donors (BD) were studied. No difference in prevalence of latent/persistent single viral infections between the patients and BD was found but dual infection rate was significantly higher in CFS patients. Active HHV-6 and dual (HHV-6 + HHV-7) infections were detected in CFS patients only and frequency of HHV-7 reactivation was also significantly higher in these patients. HHV-6 variant B was predominant in CFS patients (12/13). The changes of immunological parameters in CFS patients with active dual infection were characterized by significant decrease of CD3+ and CD4+ T cells, significant increase of CD95+ cells and decrease of CD4+/CD8+ ratio. HHV-6 and HHV-7 may be involved in the pathogenesis of CFS and reactivation of both viruses may provoke changes in the phenotype of circulating lymphocytes.

Environmental contamination in Antarctic ecosystems.

PubMed

Bargagli, R

2008-08-01

Although the remote continent of Antarctica is perceived as the symbol of the last great wilderness, the human presence in the Southern Ocean and the continent began in the early 1900s for hunting, fishing and exploration, and many invasive plant and animal species have been deliberately introduced in several sub-Antarctic islands. Over the last 50 years, the development of research and tourism have locally affected terrestrial and marine coastal ecosystems through fuel combustion (for transportation and energy production), accidental oil spills, waste incineration and sewage. Although natural "barriers" such as oceanic and atmospheric circulation protect Antarctica from lower latitude water and air masses, available data on concentrations of metals, pesticides and other persistent pollutants in air, snow, mosses, lichens and marine organisms show that most persistent contaminants in the Antarctic environment are transported from other continents in the Southern Hemisphere. At present, levels of most contaminants in Antarctic organisms are lower than those in related species from other remote regions, except for the natural accumulation of Cd and Hg in several marine organisms and especially in albatrosses and petrels. The concentrations of organic pollutants in the eggs of an opportunistic top predator such as the south polar skua are close to those that may cause adverse health effects. Population growth and industrial development in several countries of the Southern Hemisphere are changing the global pattern of persistent anthropogenic contaminants and new classes of chemicals have already been detected in the Antarctic environment. Although the Protocol on Environmental Protection to the Antarctic Treaty provides strict guidelines for the protection of the Antarctic environment and establishes obligations for all human activity in the continent and the Southern Ocean, global warming, population growth and industrial development in countries of the Southern Hemisphere will likely increase the impact of anthropogenic contaminants on Antarctic ecosystems.

Evidence for brain glial activation in chronic pain patients.

PubMed

Loggia, Marco L; Chonde, Daniel B; Akeju, Oluwaseun; Arabasz, Grae; Catana, Ciprian; Edwards, Robert R; Hill, Elena; Hsu, Shirley; Izquierdo-Garcia, David; Ji, Ru-Rong; Riley, Misha; Wasan, Ajay D; Zürcher, Nicole R; Albrecht, Daniel S; Vangel, Mark G; Rosen, Bruce R; Napadow, Vitaly; Hooker, Jacob M

2015-03-01

Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand (11)C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for (11)C-PBR28, nine patient-control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29-63 for patients and 28-65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Control of endemic swine flu persistence in farrow-to-finish pig farms: a stochastic metapopulation modeling assessment.

PubMed

Cador, Charlie; Andraud, Mathieu; Willem, Lander; Rose, Nicolas

2017-10-03

Swine influenza viruses (swIAVs) are known to persist endemically in farrow-to-finish pig farms, leading to repeated swine flu outbreaks in successive batches of pigs at a similar age (mostly around 8 weeks of age). This persistence in European swine herds involves swIAVs from European lineages including H1 av N1, H1 hu N2, H3N2, the 2009 H1N1 pandemic virus and their reassortants. The specific population dynamics of farrow-to-finish pig farms, the immune status of the animals at infection-time, the co-circulation of distinct subtypes leading to consecutive or concomitant infections have been evidenced as factors favouring swIAV persistence within herds. We developed a stochastic metapopulation model representing the co-circulation of two distinct swIAVs within a typical farrow-to-finish pig herd to evaluate the risk of reassortant viruses generation due to co-infection events. Control strategies related to herd management and/or vaccination schemes (batch-to-batch or mass vaccination of the sow herd and vaccination of growing pigs) were implemented to assess their relative efficacy regarding viral persistence. The overall probability of a co-infection event for France, possibly leading to reassortment, was evaluated to 16.8%. The export of consecutive piglets batches was identified as the most efficient measure facilitating swIAV infection fade-out. Although some vaccination schemes (batch-to-batch vaccination) had a beneficial effect in breeding sows by reducing the persistence of swIAVs within this subpopulation, none of vaccination strategies achieved swIAVs fade-out within the entire farrow-to-finish pig herd.

[The physiology of the isolated dog pancreas--the influence of the actual blood glucose level on the blood circulation in the pancreas].

PubMed

Hempfling, H; Husemann, B

1975-06-01

1. Glucose loading tests were undertaken on isolated pancreas or pancreas-duodenal preparations. 2. In 75% of cases a vasodilatation can be observed which leads to enhanced blood circulation under constant pressure in the isolated organ. 3. This vasodilatation persists until the level of blood sugar has normalized. 4. The experiment being carried out on an isolated organ, external factors such as the vagus nerve, do not become active.

Evidence for Circulation of the Rift Valley Fever Virus among Livestock in the Union of Comoros

PubMed Central

Soulé, Miradje; Faharoudine, Abdourahime; Foray, Coralie; Olive, Marie-Marie; Maquart, Marianne; Soulaimane, Abdouroihamane; Madi Kassim, Ahmed; Cêtre-Sossah, Catherine; Cardinale, Eric

2014-01-01

Rift Valley fever virus (RVFV) is an arthropod-borne phlebovirus reported to be circulating in most parts of Africa. Since 2009, RVFV has been suspected of continuously circulating in the Union of Comoros. To estimate the incidence of RVFV antibody acquisition in the Comorian ruminant population, 191 young goats and cattle were selected in six distinct zones and sampled periodically from April 2010 to August 2011. We found an estimated incidence of RVFV antibody acquisition of 17.5% (95% confidence interval (CI): [8.9–26.1]) with a significant difference between islands (8.2% in Grande Comore, 72.3% in Moheli and 5.8% in Anjouan). Simultaneously, a longitudinal entomological survey was conducted and ruminant trade-related information was collected. No RVFV RNA was detected out of the 1,568 blood-sucking caught insects, including three potential vectors of RVFV mosquito species. Our trade survey suggests that there is a continuous flow of live animals from eastern Africa to the Union of Comoros and movements of ruminants between the three Comoro islands. Finally, a cross-sectional study was performed in August 2011 at the end of the follow-up. We found an estimated RVFV antibody prevalence of 19.3% (95% CI: [15.6%–23.0%]). Our findings suggest a complex RVFV epidemiological cycle in the Union of Comoros with probable inter-islands differences in RVFV circulation patterns. Moheli, and potentially Anjouan, appear to be acting as endemic reservoir of infection whereas RVFV persistence in Grande Comore could be correlated with trade in live animals with the eastern coast of Africa. More data are needed to estimate the real impact of the disease on human health and on the national economy. PMID:25078616

Administration of herpes simplex-thymidine kinase-expressing donor T cells with a T-cell-depleted allogeneic marrow graft.

PubMed

Tiberghien, P; Ferrand, C; Lioure, B; Milpied, N; Angonin, R; Deconinck, E; Certoux, J M; Robinet, E; Saas, P; Petracca, B; Juttner, C; Reynolds, C W; Longo, D L; Hervé, P; Cahn, J Y

2001-01-01

Administration of donor T cells expressing the herpes simplex-thymidine kinase (HS-tk) with a hematopoietic stem cell (HSC) transplantation could allow, if graft-versus-host disease (GVHD) was to occur, a selective in vivo depletion of these T cells by the use of ganciclovir (GCV). The study evaluates the feasibility of such an approach. Escalating numbers of donor HS-tk-expressing CD3(+) gene-modified cells (GMCs) are infused with a T-cell-depleted bone marrow transplantation (BMT). Twelve patients with hematological malignancies received 2 x 10(5) (n = 5), 6 x 10(5) (n = 5), or 20 x 10(5) (n = 2) donor CD3(+) GMCs/kg with a BMT from a human leukocyte antigen (HLA)-identical sibling. No acute toxicity was associated with GMC administration. An early increase of circulating GMCs followed by a progressive decrease and long-lasting circulation of GMCs was documented. GCV treatment resulted in significant rapid decrease in circulating GMCs. Three patients developed acute GVHD, with a grade of at least II, while one patient developed chronic GVHD. Treatment with GCV alone was associated with a complete remission (CR) in 2 patients with acute GVHD, while the addition of glucocorticoids was necessary to achieve a CR in the last case. Long-lasting CR occurred with GCV treatment in the patient with chronic GVHD. Unfortunately, Epstein-Barr virus-lymphoproliferative disease occurred in 3 patients. Overall, the administration of low numbers of HS-tk-expressing T cells early following an HLA-identical BMT is associated with no acute toxicity, persistent circulation of the GMCs, and GCV-sensitive GVHD. Such findings open the way to the infusion of higher numbers of gene-modified donor T cells to enhance post-BMT immune competence while preserving GCV-sensitive alloreactivity.

Specific MAIT cell behaviour among innate-like T lymphocytes in critically ill patients with severe infections.

PubMed

Grimaldi, David; Le Bourhis, Lionel; Sauneuf, Bertrand; Dechartres, Agnès; Rousseau, Christophe; Ouaaz, Fatah; Milder, Maud; Louis, Delphine; Chiche, Jean-Daniel; Mira, Jean-Paul; Lantz, Olivier; Pène, Frédéric

2014-02-01

In between innate and adaptive immunity, the recently identified innate-like mucosal-associated invariant T (MAIT) lymphocytes display specific reactivity to non-streptococcal bacteria. Whether they are involved in bacterial sepsis has not been investigated. We aimed to assess the number and the time course of circulating innate-like T lymphocytes (MAIT, NKT and γδ T cells) in critically ill septic and non-septic patients and to establish correlations with the further development of intensive care unit (ICU)-acquired infections. We prospectively enrolled consecutive patients with severe sepsis and septic shock. Controls were critically ill patients with non-septic shock and age-matched healthy subjects. Circulating innate-like lymphocytes were enumerated using a flow cytometry assay at day 1, 4 and 7. One hundred and fifty six patients (113 severe bacterial infections, 36 non-infected patients and 7 patients with severe viral infections) and 26 healthy subjects were enrolled into the study. Patients with severe bacterial infections displayed an early decrease in MAIT cell count [median 1.3/mm(3); interquartile range (0.4-3.2)] as compared to control healthy subjects [31.1/mm(3) (12.1-45.2)], but also to non-infected critically ill patients [4.3/mm(3) (1.4-13.2)] (P < 0.0001 for all comparisons). In contrast NKT and γδ T cell counts did not differ between patients groups. The multivariate analysis identified non-streptococcal bacterial infection as an independent determinant of decrease in MAIT cell count. Furthermore, the incidence of ICU-acquired infections was higher in patients with persistent MAIT cell depletion. This large human study provides valuable information about MAIT cells in severe bacterial infections. The persistent depletion of MAIT cells is associated with the further development of ICU-acquired infections.

Persistence of genetic variants of the arctic fox strain of Rabies virus in southern Ontario

PubMed Central

2006-01-01

Abstract Genetic-variant analysis of rabies viruses provides the most sensitive epidemiologic tool for following the spread and persistence of these viruses in their wildlife hosts. Since its introduction by a southern epizootic movement that began in the far north, the arctic fox (AFX) strain of Rabies virus has been enzootic in Ontario for almost 50 y. Prior genetic studies identified 4 principal genetic variants (ONT.T1 to ONT.T4) that were localized to different regions of the province; furthermore, these viruses could be distinguished from the variant circulating in northern regions of Quebec, Newfoundland, and arctic zones, ARC.T5. Despite an intensive provincial control program undertaken over the last decade that involved aerial distribution of baits laden with rabies vaccine to combat fox rabies throughout the enzootic zone of Ontario, pockets of rabies activity persist. Re-evaluation of the genetic characteristics of the viral variants circulating in these areas of persistence has been undertaken. These data demonstrate that the recent outbreaks are, with 1 exception, due to persistence of the regional variant first identified in the area in the early 1990s. In contrast, the disease in the Georgian Bay area is a consequence of the incursion of a variant previously found further south. An outbreak that occurred in northern Ontario north and west of North Bay and in the neighboring border areas of Quebec in 2000–2001 was due to renewed incursion of the ARC.T5 variant from more northerly areas. PMID:16548327

Introductions and Evolution of Human-Origin Seasonal Influenza A Viruses in Multinational Swine Populations

PubMed Central

Wentworth, David E.; Culhane, Marie R.; Vincent, Amy L.; Viboud, Cecile; LaPointe, Matthew P.; Lin, Xudong; Holmes, Edward C.; Detmer, Susan E.

2014-01-01

ABSTRACT The capacity of influenza A viruses to cross species barriers presents a continual threat to human and animal health. Knowledge of the human-swine interface is particularly important for understanding how viruses with pandemic potential evolve in swine hosts. We sequenced the genomes of 141 influenza viruses collected from North American swine during 2002 to 2011 and identified a swine virus that possessed all eight genome segments of human seasonal A/H3N2 virus origin. A molecular clock analysis indicates that this virus—A/sw/Saskatchewan/02903/2009(H3N2)—has likely circulated undetected in swine for at least 7 years. For historical context, we performed a comprehensive phylogenetic analysis of an additional 1,404 whole-genome sequences from swine influenza A viruses collected globally during 1931 to 2013. Human-to-swine transmission occurred frequently over this time period, with 20 discrete introductions of human seasonal influenza A viruses showing sustained onward transmission in swine for at least 1 year since 1965. Notably, human-origin hemagglutinin (H1 and H3) and neuraminidase (particularly N2) segments were detected in swine at a much higher rate than the six internal gene segments, suggesting an association between the acquisition of swine-origin internal genes via reassortment and the adaptation of human influenza viruses to new swine hosts. Further understanding of the fitness constraints on the adaptation of human viruses to swine, and vice versa, at a genomic level is central to understanding the complex multihost ecology of influenza and the disease threats that swine and humans pose to each other. IMPORTANCE The swine origin of the 2009 A/H1N1 pandemic virus underscored the importance of understanding how influenza A virus evolves in these animals hosts. While the importance of reassortment in generating genetically diverse influenza viruses in swine is well documented, the role of human-to-swine transmission has not been as intensively studied. Through a large-scale sequencing effort, we identified a novel influenza virus of wholly human origin that has been circulating undetected in swine for at least 7 years. In addition, we demonstrate that human-to-swine transmission has occurred frequently on a global scale over the past decades but that there is little persistence of human virus internal gene segments in swine. PMID:24965467

Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Desinia B.

Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25 ppm or 1.00 ppm ozone, 5 h/day, 3 consecutive days/week (wk) for 13 wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13 wk ormore » following a 1 wk recovery period (13 wk + 1 wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13 wk, however, these responses were largely reversible following a 1 wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism. - Highlights: • Subchronic episodic ozone exposure caused pulmonary and metabolic effects. • These effects were largely reversible upon one week recovery. • Ozone exposure did not cause liver or muscle insulin resistance. • Subchronic ozone exposure led to decrease in serum insulin. • Ozone severely impaired beta cell insulin secretion in response to glucose.« less

Hydroclimate variability and regional atmospheric circulation over the past 1,350 years reconstructed from Lake Ohau, New Zealand

NASA Astrophysics Data System (ADS)

Roop, H. A.; Levy, R. H.; Vandergoes, M.; Dunbar, G. B.; Howarth, J. D.; Lorrey, A.; Phipps, S. J.

2016-12-01

Comprehensive understanding of natural climate-system dynamics requires high-resolution paleoclimate records extending beyond the instrumental period. This is particularly the case for the sparsely-instrumented Southern Hemisphere mid-latitudes, where the timing and amplitude of regional and hemispheric-scale climatic events are poorly constrained. Here we present a 1,350-year record of hydroclimatic variability and regional circulation derived from an annually laminated sediment record from Lake Ohau, South Island, New Zealand (44.23°S, 169.85°E). The climate of New Zealand is influenced by climatological patterns originating in both the tropics (e.g. El-Niño-Southern Oscillation, Interdecadal Pacific Oscillation) and the Antarctic (Southern Annular Mode, SAM). Utilizing the annually resolved Lake Ohau hydroclimate record in combination with a tree-ring record of summer temperature from Oroko Swamp, New Zealand (Cook et al., 2002), we generate a circulation index for the Western South Island of New Zealand. This index utilizes the temperature and precipitation anomalies defined by the Regional Climate Regime Classification scheme for New Zealand to assign synoptic scale circulation patterns to 25-year intervals from 900-2000 AD. This circulation index shows significant periods of change, most notably 835 - 985 AD when northerly airflow dominated and from 1385 - 1710 AD when strong southerly airflow persisted. Comparisons with regional SAM and ENSO reconstructions show that dry, warm conditions at Lake Ohau are consistently associated with strengthened tropical teleconnections to New Zealand and a positive SAM, while cold and wet conditions are driven by increased southerly airflow and negative phase SAM. A persistent negative SAM dominates the Little Ice Age (LIA; 1385-1710 AD) interval in the Western South Island. This same period coincides with the Northern Hemisphere LIA.

Fetal in vivo continuous cardiovascular function during chronic hypoxia

PubMed Central

Allison, B. J.; Brain, K. L.; Niu, Y.; Kane, A. D.; Herrera, E. A.; Thakor, A. S.; Botting, K. J.; Cross, C. M.; Itani, N.; Skeffington, K. L.; Beck, C.

2016-01-01

Key points The in vivo fetal cardiovascular defence to chronic hypoxia has remained by and large an enigma because no technology has been available to induce significant and prolonged fetal hypoxia whilst recording longitudinal changes in fetal regional blood flow as the hypoxic pregnancy is developing.We introduce a new technique able to maintain chronically instrumented maternal and fetal sheep preparations under isobaric chronic hypoxia for most of gestation, beyond levels that can be achieved by high altitude and of relevance in magnitude to the human intrauterine growth‐restricted fetus.This technology permits wireless recording in free‐moving animals of longitudinal maternal and fetal cardiovascular function, including beat‐to‐beat alterations in pressure and blood flow signals in regional circulations.The relevance and utility of the technique is presented by testing the hypotheses that the fetal circulatory brain sparing response persists during chronic fetal hypoxia and that an increase in reactive oxygen species in the fetal circulation is an involved mechanism. Abstract Although the fetal cardiovascular defence to acute hypoxia and the physiology underlying it have been established for decades, how the fetal cardiovascular system responds to chronic hypoxia has been comparatively understudied. We designed and created isobaric hypoxic chambers able to maintain pregnant sheep for prolonged periods of gestation under controlled significant (10% O2) hypoxia, yielding fetal mean PaO2 levels (11.5 ± 0.6 mmHg) similar to those measured in human fetuses of hypoxic pregnancy. We also created a wireless data acquisition system able to record fetal blood flow signals in addition to fetal blood pressure and heart rate from free moving ewes as the hypoxic pregnancy is developing. We determined in vivo longitudinal changes in fetal cardiovascular function including parallel measurement of fetal carotid and femoral blood flow and oxygen and glucose delivery during the last third of gestation. The ratio of oxygen (from 2.7 ± 0.2 to 3.8 ± 0.8; P < 0.05) and of glucose (from 2.3 ± 0.1 to 3.3 ± 0.6; P < 0.05) delivery to the fetal carotid, relative to the fetal femoral circulation, increased during and shortly after the period of chronic hypoxia. In contrast, oxygen and glucose delivery remained unchanged from baseline in normoxic fetuses. Fetal plasma urate concentration increased significantly during chronic hypoxia but not during normoxia (Δ: 4.8 ± 1.6 vs. 0.5 ± 1.4 μmol l−1, P<0.05). The data support the hypotheses tested and show persisting redistribution of substrate delivery away from peripheral and towards essential circulations in the chronically hypoxic fetus, associated with increases in xanthine oxidase‐derived reactive oxygen species. PMID:26926316

Life cycles of persistent anomalies. I - Evolution of 500 mb height fields

NASA Technical Reports Server (NTRS)

Dole, Randall M.

1989-01-01

The life cycles of persistent anomalies of the extratropical Northern Hemisphere wintertime circulation are studied, focusing on the typical characteristics of the 500 mb height anomaly and flow patterns accompanying the development and breakdown of large-scale flow anomalies in the eastern North Atlantic and the northern Soviet Union. Following onset, anomaly centers develop and intensify in sequence downstream from the main center, forming a quasi-stationary wavetrain pattern. From development through decay, corresponding positive and negative patterns have similar evolutions.

Quantification of temperature persistence over the Northern Hemisphere land-area

NASA Astrophysics Data System (ADS)

Pfleiderer, Peter; Coumou, Dim

2017-10-01

Extreme weather events such as heat waves and floods are damaging to society and their contribution to future climate impacts is expected to be large. Such extremes are often related to persistent local weather conditions. Weather persistence is linked to sea surface temperatures, soil-moisture (especially in summer) and large-scale circulation patterns and these factors can alter under past and future climate change. Though persistence is a key characteristic for extreme weather events, to date the climatology and potential changes in persistence have only been poorly documented. Here, we present a systematic analysis of temperature persistence for the northern hemisphere land area. We define persistence as the length of consecutive warm or cold days and use spatial clustering techniques to create regional persistence distributions. We find that persistence is longest in the Arctic and shortest in the mid-latitudes. Parameterizations of the regional persistence distributions show that they are characterized by an exponential decay with a drop in the decay rate for very persistent events, implying that feedback mechanisms are important in prolonging these events. For the mid-latitudes, we find that persistence in summer has increased over the past 60 years. The changes are particularly pronounced for prolonged events suggesting a lengthening in the duration of heat waves.

Electrophysiological effects of acute atrial stretch on persistent atrial fibrillation in patients undergoing open heart surgery.

PubMed

Elvan, Arif; Adiyaman, Ahmet; Beukema, Rypko J; Sie, Hauw T; Allessie, Maurits A

2013-03-01

The electrophysiologic effects of acute atrial dilatation and dedilatation in humans with chronic atrial fibrillation remains to be elucidated. To study the electrophysiological effects of acute atrial dedilatation and subsequent dilatation in patients with long-standing persistent atrial fibrillation (AF) with structural heart disease undergoing elective cardiac surgery. Nine patients were studied. Mean age was 71 ± 10 years, and left ventricular ejection was 46% ± 6%. Patients had at least moderate mitral valve regurgitation and dilated atria. After sternotomy and during extracorporal circulation, mapping was performed on the beating heart with 2 multielectrode arrays (60 electrodes each, interelectrode distance 1.5 mm) positioned on the lateral wall of the right atrium (RA) and left atrium (LA). Atrial pressure and size were altered by modifying extracorporal circulation. AF electrograms were recorded at baseline after dedilation and after dilatation of the atria afterward. At baseline, the median AF cycle length (mAFCL) was 184 ± 27 ms in the RA and 180 ± 17 ms in the LA. After dedilatation, the mAFCL shortened significantly to 168 ± 13 ms in the RA and to 168 ± 20 ms in the LA. Dilatation lengthened mAFCL significantly to 189 ± 17 ms in the RA and to 185 ± 23 ms in the LA. Conduction block (CB) at baseline was 14.3% ± 3.6% in the RA and 17.3% ± 5.5% in the LA. CB decreased significantly with dedilatation to 7.4% ± 2.9% in the RA and to 7.9% ± 6.3% in the LA. CB increased significantly with dilatation afterward to 15.0% ± 8.3% in the RA and to 18.5% ± 16.0% in the LA. Acute dedilatation of the atria in patients with long-standing persistent AF causes a decrease in the mAFCL in both atria. Subsequent dilatation increased the mAFCL. The amount of CB decreased with dedilatation and increased with dilatation afterward in both atria. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Decreases in circulating uncarboxylated osteocalcin are not associated with HOMA-IR changes in humans

USDA-ARS?s Scientific Manuscript database

Osteocalcin (OC) in its uncarboxylated form (ucOC) may improve glucose metabolism in mice. However, human data are equivocal. Vitamin K (VK) is the only known factor to reduce the proportion of circulating OC that is uncarboxylated. We hypothesized that a decrease in circulating ucOC through VK supp...

Circulating human papillomavirus DNA detected using droplet digital PCR in the serum of patients diagnosed with early stage human papillomavirus-associated invasive carcinoma.

PubMed

Jeannot, Emmanuelle; Becette, Véronique; Campitelli, Maura; Calméjane, Marie-Ange; Lappartient, Emmanuelle; Ruff, Evelyne; Saada, Stéphanie; Holmes, Allyson; Bellet, Dominique; Sastre-Garau, Xavier

2016-10-01

Specific human papillomavirus genotypes are associated with most ano-genital carcinomas and a large subset of oro-pharyngeal carcinomas. Human papillomavirus DNA is thus a tumour marker that can be detected in the blood of patients for clinical monitoring. However, data concerning circulating human papillomavirus DNA in cervical cancer patients has provided little clinical value, due to insufficient sensitivity of the assays used for the detection of small sized tumours. Here we took advantage of the sensitive droplet digital PCR method to identify circulating human papillomavirus DNA in patients with human papillomavirus-associated carcinomas. A series of 70 serum specimens, taken at the time of diagnosis, between 2002 and 2013, were retrospectively analyzed in patients with human papillomavirus-16 or human papillomavirus-18-associated carcinomas, composed of 47 cases from the uterine cervix, 15 from the anal canal and 8 from the oro-pharynx. As negative controls, 18 serum samples from women with human papillomavirus-16-associated high-grade cervical intraepithelial neoplasia were also analyzed. Serum samples were stored at -80°C (27 cases) or at -20°C (43 cases). DNA was isolated from 200 µl of serum or plasma and droplet digital PCR was performed using human papillomavirus-16 E7 and human papillomavirus-18 E7 specific primers. Circulating human papillomavirus DNA was detected in 61/70 (87%) serum samples from patients with carcinoma and in no serum from patients with cervical intraepithelial neoplasia. The positivity rate increased to 93% when using only serum stored at -80°C. Importantly, the two patients with microinvasive carcinomas in this series were positive. Quantitative evaluation showed that circulating viral DNA levels in cervical cancer patients were related to the clinical stage and tumour size, ranging from 55 ± 85 copies/ml (stage I) to 1774 ± 3676 copies/ml (stage IV). Circulating human papillomavirus DNA is present in patients with human papillomavirus-associated invasive cancers even at sub-clinical stages and its level is related to tumour dynamics. Droplet digital PCR is a promising method for circulating human papillomavirus DNA detection and quantification. No positivity was found in patients with human papillomavirus-associated high grade cervical intraepithelial neoplasia.

Circulating human papillomavirus DNA detected using droplet digital PCR in the serum of patients diagnosed with early stage human papillomavirus‐associated invasive carcinoma

PubMed Central

Jeannot, Emmanuelle; Becette, Véronique; Campitelli, Maura; Calméjane, Marie‐Ange; Lappartient, Emmanuelle; Ruff, Evelyne; Saada, Stéphanie; Holmes, Allyson; Bellet, Dominique

2016-01-01

Abstract Specific human papillomavirus genotypes are associated with most ano‐genital carcinomas and a large subset of oro‐pharyngeal carcinomas. Human papillomavirus DNA is thus a tumour marker that can be detected in the blood of patients for clinical monitoring. However, data concerning circulating human papillomavirus DNA in cervical cancer patients has provided little clinical value, due to insufficient sensitivity of the assays used for the detection of small sized tumours. Here we took advantage of the sensitive droplet digital PCR method to identify circulating human papillomavirus DNA in patients with human papillomavirus‐associated carcinomas. A series of 70 serum specimens, taken at the time of diagnosis, between 2002 and 2013, were retrospectively analyzed in patients with human papillomavirus‐16 or human papillomavirus‐18‐associated carcinomas, composed of 47 cases from the uterine cervix, 15 from the anal canal and 8 from the oro‐pharynx. As negative controls, 18 serum samples from women with human papillomavirus‐16‐associated high‐grade cervical intraepithelial neoplasia were also analyzed. Serum samples were stored at −80°C (27 cases) or at −20°C (43 cases). DNA was isolated from 200 µl of serum or plasma and droplet digital PCR was performed using human papillomavirus‐16 E7 and human papillomavirus‐18 E7 specific primers. Circulating human papillomavirus DNA was detected in 61/70 (87%) serum samples from patients with carcinoma and in no serum from patients with cervical intraepithelial neoplasia. The positivity rate increased to 93% when using only serum stored at −80°C. Importantly, the two patients with microinvasive carcinomas in this series were positive. Quantitative evaluation showed that circulating viral DNA levels in cervical cancer patients were related to the clinical stage and tumour size, ranging from 55 ± 85 copies/ml (stage I) to 1774 ± 3676 copies/ml (stage IV). Circulating human papillomavirus DNA is present in patients with human papillomavirus‐associated invasive cancers even at sub‐clinical stages and its level is related to tumour dynamics. Droplet digital PCR is a promising method for circulating human papillomavirus DNA detection and quantification. No positivity was found in patients with human papillomavirus‐associated high grade cervical intraepithelial neoplasia. PMID:27917295

Pathogenesis of parvovirus B19 infection: host gene variability, and possible means and effects of virus persistence.

PubMed

Kerr, J R

2005-01-01

Since conducting follow-up studies of patients with acute symptomatic parvovirus B19 infection which showed that a significant proportion of patients develop prolonged arthritis and chronic fatigue syndrome (CFS), we have become interested in the mechanisms of this phenomenon. We showed that these cases have high levels of pro-inflammatory cytokines in their circulation and that this correlates with the symptoms. However, the underlying mechanisms were not apparent, and we have used various approaches to begin studying this phenomenon. DNA polymorphisms were looked for and several were shown to be more common in these subjects compared with controls; these occur within genes of both the immune response [human leucocyte antigen (HLA)-DRB1, HLA-B, transforming growth factor (TGF)-beta1] and those involved in several other cellular functions (predominantly the cytoskeleton and cell adhesion). Interestingly, one particular single-nucleotide polymorphism (SNP) which is associated with symptomatic B19 infection occurs in the Ku80 gene which has recently been shown to be a B19 co-receptor. B19 persistence is probably the key to this phenomenon, and some new data are presented on short regions of sequence homology (17-26 bp) between human, mouse and rat parvoviruses and their respective hosts which occur in many host genes. This homology may provide a foothold for virus persistence and may also play a role in the genesis of disease through gene disruption. Finally, we used microarrays and TaqMan real-time polymerase chain reaction in 108 normal persons to study human gene expression in persons who are B19-seropositive versus B19-seronegative (age- and sex-matched) to examine the hypothesis that gene regulation may be altered in subjects harbouring the B19 virus DNA. Six genes were found to be differentially expressed with roles in the cytoskeleton (SKIP, MACF1, SPAG7, FLOT1), integrin signalling (FLOT1, RASSF5), HLA class III (c6orf48), and tumour suppression (RASSF5). These results have implications not only for B19 but also for other persistent viruses as well and confirmation is required. In conclusion, these disparate findings contribute to our understanding of the pathogenesis of B19 disease. We are using these studies as a starting point to study the phenomenon of chronic immune activation following B19 infection.

Retinal vascular changes are a marker for cerebral vascular diseases

PubMed Central

Moss, Heather E.

2016-01-01

The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk. PMID:26008809

Assessment of toxic potential of mycotoxin contaminated bread during in vitro human digestion on human B lymphoid cell line.

PubMed

Monaci, Linda; Garbetta, Antonella; Angelis, Elisabetta De; Visconti, Angelo; Minervini, Fiorenza

2015-01-05

Ingestion of food is considered a major route of exposure to many contaminants including mycotoxins. The amount of mycotoxin resisting to the digestion process and potentially absorbable by the systemic circulation is only a smaller part of that ingested. In vitro digestion models turn useful for evaluating mycotoxins bioaccessibility during the intestinal transit and can be intended as a valuable tool for the assessment of mycotoxin bioavailability in food. In this paper we describe a study aimed at investigating toxicity of in vitro gastro-duodenal digests of mycotoxin contaminated bread collected along the digestion time-course. Toxicity tests were carried out on a sensitive RPMI lymphoid B cell line chosen as the most suitable lineage to assess toxicity retained by gastro-duodenal digests. In parallel, a chemical quantification of T-2 and HT-2 toxins contaminating the bread digests was accomplished during the gastric and duodenal transit. The digestive fluids undergoing chemical and toxicological analysis were collected at the beginning and end of gastric phase, and after completion of the duodenal phase. Results proved that a correlation between HT-2 content and toxicity did exist although a more persistent toxic activity was displayed in the later stage of the duodenal phase. This persistent toxicity might be explained by the co-occurrence of unknown HT-2-related conjugates or metabolites formed during digestion. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Frequency and genotype of human parvovirus B19 among Iranian patients infected with HIV.

PubMed

Azadmanesh, Kayhan; Mohraz, Minoo; Kazemimanesh, Monireh; Aghakhani, Arezoo; Foroughi, Maryam; Banifazl, Mohammad; Eslamifar, Ali; Ramezani, Amitis

2015-07-01

The human parvovirus B19 (B19) usually causes a subclinical infection in immunocompetent individuals. Whereas immunocompromised individuals such as patients infected with HIV are at risk of persistent anemia due to B19 infection. Only few studies have been carried out on distribution and molecular epidemiology of B19 in Iran. We aimed to determine the frequency and genotype of B19 among Iranian patients infected with HIV. We conducted a survey on 99 HIV patients and 64 healthy controls. IgG and IgM antibodies against B19 were detected by ELISA and B19 DNA was assessed by nested PCR. PCR products were subjected to direct sequencing and classified after phylogenetic analysis. The prevalence of B19 immunoglobulin was 11.1% for IgG and 1% for IgM. B19 DNA was detected in 13.1% of cases. The prevalence of B19 IgG, IgM, and DNA in control group was 25%, 1.6%, and 9.4%, respectively. B19 IgG was significantly lower in HIV group than in normal controls. There was no significant difference regarding anemia between cases and controls. All sequenced B19 isolates belonged to genotype 1A with low genetic diversity. Our findings indicated that in the HAART era, the importance of B19 infections in HIV patients may be limited whereas persistent B19 viremia in the circulation of healthy controls raises a potential concern in blood donations. © 2015 Wiley Periodicals, Inc.

Seroepidemiology of Selected Arboviruses in Febrile Patients Visiting Selected Health Facilities in the Lake/River Basin Areas of Lake Baringo, Lake Naivasha, and Tana River, Kenya

PubMed Central

Lwande, Olivia; Orindi, Benedict; Irura, Zephania; Ongus, Juliette; Sang, Rosemary

2015-01-01

Abstract Introduction: Arboviruses cause emerging and re-emerging infections affecting humans and animals. They are spread primarily by blood-sucking insects such as mosquitoes, ticks, midges, and sandflies. Changes in climate, ecology, demographic, land-use patterns, and increasing global travel have been linked to an upsurge in arboviral disease. Outbreaks occur periodically followed by persistent low-level circulation. Aim: This study was undertaken to determine the seroepidemiology of selected arboviruses among febrile patients in selected lake/river basins of Kenya. Methods: Using a hospital-based cross-sectional descriptive survey, febrile patients were recruited and their serum samples tested for exposure to immunoglobulin M (IgM) and IgG antibodies against Crimean–Congo hemorrhagic fever virus (CCHFV), Rift Valley fever virus (RVFV), West Nile virus (WNV), and chikungunya virus (CHIKV). Samples positive for CHIKV and WNV were further confirmed by the plaque reduction neutralization test (PRNT). Results: Of the 379 samples examined, 176 were IgG positive for at least one of these arboviruses (46.4%, 95% confidence interval [CI] 41.4–51.5%). Virus-specific prevalence for CCHF, RVF, WN, and CHIK was 25.6%, 19.5%, 12.4%, and 2.6%, respectively. These prevalences varied significantly with geographical site (p<0.001), with Tana recording the highest overall arboviral seropositivity. PRNT results for Alphaviruses confirmed that the actual viruses circulating in Baringo were Semliki Forest virus (SFV) and CHIKV, o'nyong nyong virus (ONNV) in Naivasha, and SFV and Sindbis virus (SINDV) in Tana delta. Among the flaviviruses tested, WNV was circulating in all the three sites. Conclusion: There is a high burden of febrile illness in humans due to CCHFV, RVFV, WNV, and CHIKV infection in the river/lake basin regions of Kenya. PMID:25700043

Compaction-Driven Evolution of Pluto's Rocky Core: Implications for Water-Rock Interactions

NASA Astrophysics Data System (ADS)

Gabasova, L. R.; Tobie, G.; Choblet, G.

2018-05-01

We model the compaction of Pluto's rocky core after accretion and explore the potential for hydrothermal circulation within the porous layer, as well as examine its effect on core cooling and the persistence of a liquid internal ocean.

Persistent, circulative transmission of begomoviruses by whitefly vectors

USDA-ARS?s Scientific Manuscript database

Begomoviruses comprise an emerging and economically important group of plant viruses exclusively transmitted by the sweetpotato whitefly Bemisia tabaci in many regions of the world. The past twenty years have witnessed significant progress in studying the molecular interactions between members of th...

Three types of Indian Ocean Basin modes

NASA Astrophysics Data System (ADS)

Guo, Feiyan; Liu, Qinyu; Yang, Jianling; Fan, Lei

2017-04-01

The persistence of the Indian Ocean Basin Mode (IOBM) from March to August is important for the prediction of Asian summer monsoon. Based on the observational data and the pre-industrial control run outputs of the Community Climate System Model, version 4 (CCSM4), the IOBM is categorized into three types: the first type can persist until August; the second type transforms from the positive (negative) IOBM into the negative (positive) Indian Ocean Dipole Mode (IODM), accompanied by the El Niño-to-La Niña (La Niña-to-El Niño) transition in the boreal summer; the third type transforms from the positive (negative) IOBM into the positive (negative) IODM in early summer. It is discovered that aside from the influence of anomalous Walker Circulation resulted from the phase transition of ENSO, the persistence of Australia high anomaly (AHA) over the southeastern tropical Indian Ocean (TIO) and the west of Australia from March to May is favorable for the positive (negative) IOBM transformation into the positive (negative) IODM in the boreal summer. The stronger equatorially asymmetric sea surface temperature anomalies (SSTAs) in the boreal spring are the main mechanism for the persistence of IOBM, because the asymmetric atmospheric responses to the stronger equatorially asymmetric SSTAs in the TIO confine the AHA to the east of Australia from May to August. This result indicates a possibility of predicting summer atmospheric circulation based on the equatorial symmetry of SSTAs in the TIO in spring.

Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity

PubMed Central

Adusumilli, Prasad S.; Cherkassky, Leonid; Villena-Vargas, Jonathan; Colovos, Christos; Servais, Elliot; Plotkin, Jason; Jones, David R.; Sadelain, Michel

2015-01-01

Translating the recent success of chimeric antigen receptor (CAR) T cell therapy for hematological malignancies to solid tumors will necessitate overcoming several obstacles, including inefficient T cell tumor infiltration and insufficient functional persistence. Taking advantage of an orthotopic model that faithfully mimics human pleural malignancy, we evaluated two routes of administration of mesothelin-targeted T cells using the M28z CAR. We found that intra-pleurally administered CAR T cells vastly out-performed systemically infused T cells, requiring 30-fold fewer M28z T cells to induce long-term complete remissions. Following intrapleural T cell administration, prompt in vivo antigen-induced T cell activation allowed robust CAR T cell expansion and effector differentiation, resulting in enhanced anti-tumor efficacy and functional T cell persistence for 200 days. Regional T cell administration also promoted efficient elimination of extrathoracic tumor sites. This therapeutic efficacy was dependent on early CD4+ T cell activation associated with a higher intra-tumoral CD4/CD8 cell ratios and CD28-dependent CD4+ T cell-mediated cytotoxicity. In contrast, intravenously delivered CAR T cells, even when accumulated at equivalent numbers in the pleural tumor, did not achieve comparable activation, tumor eradication or persistence. The remarkable ability of intrapleurally administered T cells to circulate and persist supports the concept of delivering optimal CAR T cell therapy through “regional distribution centers.” Based on these results, we are opening a phase I clinical trial to evaluate the safety of intrapleural administration of mesothelin-targeted CAR T cells in patients with primary or secondary pleural malignancies. PMID:25378643

Implications of Efficient Hepatic Delivery by Tenofovir Alafenamide (GS-7340) for Hepatitis B Virus Therapy

PubMed Central

Wang, Ting; Park, Yeojin; Hao, Jia; Lepist, Eve-Irene; Babusis, Darius; Ray, Adrian S.

2015-01-01

Tenofovir alafenamide (TAF) is a prodrug of tenofovir (TFV) currently in clinical evaluation for treatment for HIV and hepatitis B virus (HBV) infections. Since the target tissue for HBV is the liver, the hepatic delivery and metabolism of TAF in primary human hepatocytes in vitro and in dogs in vivo were evaluated here. Incubation of primary human hepatocytes with TAF resulted in high levels of the pharmacologically active metabolite tenofovir diphosphate (TFV-DP), which persisted in the cell with a half-life of >24 h. In addition to passive permeability, studies of transfected cell lines suggest that the hepatic uptake of TAF is also facilitated by the organic anion-transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3, respectively). In order to inhibit HBV reverse transcriptase, TAF must be converted to the pharmacologically active form, TFV-DP. While cathepsin A is known to be the major enzyme hydrolyzing TAF in cells targeted by HIV, including lymphocytes and macrophages, TAF was primarily hydrolyzed by carboxylesterase 1 (CES1) in primary human hepatocytes, with cathepsin A making a small contribution. Following oral administration of TAF to dogs for 7 days, TAF was rapidly absorbed. The appearance of the major metabolite TFV in plasma was accompanied by a rapid decline in circulating TAF. Consistent with the in vitro data, high and persistent levels of TFV-DP were observed in dog livers. Notably, higher liver TFV-DP levels were observed after administration of TAF than those given TDF. These results support the clinical testing of once-daily low-dose TAF for the treatment of HBV infection. PMID:25870059

Trends in winter circulation over the British Isles and central Europe in twenty-first century projections by 25 CMIP5 GCMs

NASA Astrophysics Data System (ADS)

Stryhal, Jan; Huth, Radan

2018-03-01

Winter midlatitude atmospheric circulation has been extensively studied for its tight link to surface weather, and automated circulation classifications have often been used to this end. Here, eight such classifications are applied to daily sea level pressure patterns simulated by an ensemble of CMIP5 GCMs twenty-first century projections for the British Isles and central Europe in order to robustly estimate future changes in frequency, persistence, and strength of synoptic-scale circulation there. All methods are able to identify present-day biases of models reported before, such as an overestimated occurrence of zonal flow and underestimation of anticyclonic conditions and easterly advection, although the strength of these biases varies among the methods. In future, models show that the zonal flow will become more frequent while the strength of the mean flow is not projected to change. Over the British Isles, the models that better simulate the latitude of zonal flow over the historical period indicate a slight equatorward shift of westerlies in their projections, while the poleward expansion of circulation—expected in future at global scale—is apparent in those models that have large errors. Over central Europe, some classifications indicate an increase in persistence and especially in frequency of anticyclonic types, which is, however, shown to be rather an artifact of some methods than a real feature. On the other hand, the easterly flow is robustly projected to become markedly weaker in central Europe, which we hypothesize might be an important factor contributing to the projected decrease of cold extremes there.

Evidence of Local Persistence of Human Anthrax in the Country of Georgia Associated with Environmental and Anthropogenic Factors

PubMed Central

Kracalik, Ian T.; Malania, Lile; Tsertsvadze, Nikoloz; Manvelyan, Julietta; Bakanidze, Lela; Imnadze, Paata; Tsanava, Shota; Blackburn, Jason K.

2013-01-01

Background Anthrax is a soil-borne disease caused by the bacterium Bacillus anthracis and is considered a neglected zoonosis. In the country of Georgia, recent reports have indicated an increase in the incidence of human anthrax. Identifying sub-national areas of increased risk may help direct appropriate public health control measures. The purpose of this study was to evaluate the spatial distribution of human anthrax and identify environmental/anthropogenic factors associated with persistent clusters. Methods/Findings A database of human cutaneous anthrax in Georgia during the period 2000–2009 was constructed using a geographic information system (GIS) with case data recorded to the community location. The spatial scan statistic was used to identify persistence of human cutaneous anthrax. Risk factors related to clusters of persistence were modeled using a multivariate logistic regression. Areas of persistence were identified in the southeastern part of the country. Results indicated that the persistence of human cutaneous anthrax showed a strong positive association with soil pH and urban areas. Conclusions/Significance Anthrax represents a persistent threat to public and veterinary health in Georgia. The findings here showed that the local level heterogeneity in the persistence of human cutaneous anthrax necessitates directed interventions to mitigate the disease. High risk areas identified in this study can be targeted for public health control measures such as farmer education and livestock vaccination campaigns. PMID:24040426

FXR activation by obeticholic acid or nonsteroidal agonists induces a human-like lipoprotein cholesterol change in mice with humanized chimeric liver.

PubMed

Papazyan, Romeo; Liu, Xueqing; Liu, Jingwen; Dong, Bin; Plummer, Emily M; Lewis, Ronald D; Roth, Jonathan D; Young, Mark A

2018-06-01

Obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist that regulates bile acid and lipid metabolism. FXR activation induces distinct changes in circulating cholesterol among animal models and humans. The mechanistic basis of these effects has been elusive because of difficulties in studying lipoprotein homeostasis in mice, which predominantly package circulating cholesterol in HDLs. Here, we tested the effects of OCA in chimeric mice whose livers are mostly composed (≥80%) of human hepatocytes. Chimeric mice exhibited a human-like ratio of serum LDL cholesterol (LDL-C) to HDL cholesterol (HDL-C) at baseline. OCA treatment in chimeric mice increased circulating LDL-C and decreased circulating HDL-C levels, demonstrating that these mice closely model the cholesterol effects of FXR activation in humans. Mechanistically, OCA treatment increased hepatic cholesterol in chimeric mice but not in control mice. This increase correlated with decreased SREBP-2 activity and target gene expression, including a significant reduction in LDL receptor protein. Cotreatment with atorvastatin reduced total cholesterol, rescued LDL receptor protein levels, and normalized serum LDL-C. Treatment with two clinically relevant nonsteroidal FXR agonists elicited similar lipoprotein and hepatic changes in chimeric mice, suggesting that the increase in circulating LDL-C is a class effect of FXR activation.

H pylori status and angiogenesis factors in human gastric carcinoma

PubMed Central

Mangia, Anita; Chiriatti, Annalisa; Ranieri, Girolamo; Abbate, Ines; Coviello, Maria; Simone, Giovanni; Zito, Francesco Alfredo; Montemurro, Severino; Rucci, Antonello; Leo, Alfredo Di; Tommasi, Stefania; Berloco, Pasquale; Xu, Jian Ming; Paradiso, Angelo

2006-01-01

AIM: To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density (MVD), thymidine phosphorylase (TP), vascular endothelial growth factor receptor-1 (VEGF-R1), p53 and circulating VEGF levels. METHODS: Angiogenic markers were analyzed immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin (vacA) and the cytotoxin-associated gene (cagA) amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELISA, respectively. RESULTS: A total of 69% of patients were positive for circulating IgG antibodies against H pylori. cagA-positive H pylori strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was significantly associated with cagA (P = 0.0001). MVD was significantly correlated with both tumor VEGF expression (r = 0.361, P = 0.009) and serum VEGF levels (r = -0.347, P = 0.041). Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level (P = 0.026). CONCLUSION: H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic characteristics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical disease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent. PMID:17006982

Medical Complications of the Critically Ill Newborn: A Review for Early Intervention Professionals.

ERIC Educational Resources Information Center

McNab, Theresa C.; Blackman, James A.

1998-01-01

Provides early-intervention professionals with a basic familiarity and understanding of some of the newest technologies employed in the neonatal intensive care units for neonates with respiratory distress syndrome, persistent fetal circulation, retinopathy of prematurity, intraventricular hemorrhage, and periventricular leukomalacia. Early…

Hawaii cohort study of serum micronutrient concentrations and clearance of incident oncogenic human papillomavirus infection of the cervix.

PubMed

Goodman, Marc T; Shvetsov, Yurii B; McDuffie, Katharine; Wilkens, Lynne R; Zhu, Xuemei; Franke, Adrian A; Bertram, Cathy Cramer; Kessel, Bruce; Bernice, Marge; Sunoo, Christian; Ning, Lily; Easa, David; Killeen, Jeffrey; Kamemoto, Lori; Hernandez, Brenda Y

2007-06-15

The degree to which the resolution of human papillomavirus (HPV) infection parallels exposure to other factors, particularly those related to nutritional status, is a relatively unexplored area of research. We established a cohort of women for long-term follow-up to examine the association of serum retinol, carotenoid, and tocopherol concentrations with the clearance of incident cervical HPV infection. Interviews and biological specimens were obtained at baseline and at 4-month intervals. At each visit, a cervical cell specimen for HPV DNA analysis and cytology and a fasting blood sample to measure micronutrient levels were collected. A Cox proportional hazards model was used to study the relationship between clearance of 189 incident (type-specific) oncogenic HPV infections and the levels of 20 serum micronutrients among 122 women. Higher circulating levels of trans-zeaxanthin, total trans-lutein/zeaxanthin, cryptoxanthin (total and beta), total trans-lycopene and cis-lycopene, carotene (alpha, beta, and total), and total carotenoids were associated with a significant decrease in the clearance time of type-specific HPV infection, particularly during the early stages of infection (120 days) was not significantly associated with circulating levels of carotenoids or tocopherols. Results from this investigation support an association of micronutrients with the rapid clearance of incident oncogenic HPV infection of the uterine cervix.

A brief history of the discovery of the circulation of blood in the human body.

PubMed

Azizi, Mohammad-Hossein; Nayernouri, Touraj; Azizi, Farzaneh

2008-05-01

The present article describes briefly the development of the theories regarding the circulation of blood in humans, from the time of Galen (second century C.E.) to the work of William Harvey (17th century C.E.).We shall summarize the views of Galen together with those of two prominent Iranian physicians of the Middle Ages (Razi and Ahwazi known in the West as Rhazes and Haly Abbas respectively) as well as that of Ibn-Nafis from Damascus (the discoverer of the pulmonary circulation) and the Spanish physician and cleric Michael Servetus and finally the definitive work of William Harvey, the English physician who described the mechanism of both the systemic and pulmonary circulation of blood in the human body.

Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease.

PubMed

Pettigrew, Melinda M; Ahearn, Christian P; Gent, Janneane F; Kong, Yong; Gallo, Mary C; Munro, James B; D'Mello, Adonis; Sethi, Sanjay; Tettelin, Hervé; Murphy, Timothy F

2018-04-03

Nontypeable Haemophilus influenzae (NTHi) exclusively colonize and infect humans and are critical to the pathogenesis of chronic obstructive pulmonary disease (COPD). In vitro and animal models do not accurately capture the complex environments encountered by NTHi during human infection. We conducted whole-genome sequencing of 269 longitudinally collected cleared and persistent NTHi from a 15-y prospective study of adults with COPD. Genome sequences were used to elucidate the phylogeny of NTHi isolates, identify genomic changes that occur with persistence in the human airways, and evaluate the effect of selective pressure on 12 candidate vaccine antigens. Strains persisted in individuals with COPD for as long as 1,422 d. Slipped-strand mispairing, mediated by changes in simple sequence repeats in multiple genes during persistence, regulates expression of critical virulence functions, including adherence, nutrient uptake, and modification of surface molecules, and is a major mechanism for survival in the hostile environment of the human airways. A subset of strains underwent a large 400-kb inversion during persistence. NTHi does not undergo significant gene gain or loss during persistence, in contrast to other persistent respiratory tract pathogens. Amino acid sequence changes occurred in 8 of 12 candidate vaccine antigens during persistence, an observation with important implications for vaccine development. These results indicate that NTHi alters its genome during persistence by regulation of critical virulence functions primarily by slipped-strand mispairing, advancing our understanding of how a bacterial pathogen that plays a critical role in COPD adapts to survival in the human respiratory tract.

Evaluation of Two Commercial Enzyme-Linked Immunosorbent Assay Kits for the Detection of Human Circulating Metrnl.

PubMed

Zheng, Si-Li; Li, Zhi-Yong; Zhang, Zheng; Wang, Dong-Sheng; Xu, Jian; Miao, Chao-Yu

2018-04-01

Metrnl is a newly discovered secreted protein with neurotrophic activity and metabolic effect, while in earlier studies its circulating level in human was not explored. We evaluated two commercial enzyme-linked immunosorbent assay kits (DY7867-05, R&D Systems and SK00478-02, Aviscera Bioscience) for the detection of human circulating Metrnl. The DY7867-05 kit showed superiority over the SK00478-02 kit since it generated better curve fitting degree, smaller variation among tests, higher inter-assay reproducibility and better specificity, and could effectively detect human Metrnl in six types of blood samples. Subsequent analysis was performed using the DY7867-05 kit. Sample storage conditions were investigated. No gender difference in circulating Metrnl levels was found, while people with newly diagnosed type 2 diabetes mellitus (T2DM) had significantly lower Metrnl levels compared to the healthy controls.

Genetic Modification of the Lung Directed Toward Treatment of Human Disease.

PubMed

Sondhi, Dolan; Stiles, Katie M; De, Bishnu P; Crystal, Ronald G

2017-01-01

Genetic modification therapy is a promising therapeutic strategy for many diseases of the lung intractable to other treatments. Lung gene therapy has been the subject of numerous preclinical animal experiments and human clinical trials, for targets including genetic diseases such as cystic fibrosis and α1-antitrypsin deficiency, complex disorders such as asthma, allergy, and lung cancer, infections such as respiratory syncytial virus (RSV) and Pseudomonas, as well as pulmonary arterial hypertension, transplant rejection, and lung injury. A variety of viral and non-viral vectors have been employed to overcome the many physical barriers to gene transfer imposed by lung anatomy and natural defenses. Beyond the treatment of lung diseases, the lung has the potential to be used as a metabolic factory for generating proteins for delivery to the circulation for treatment of systemic diseases. Although much has been learned through a myriad of experiments about the development of genetic modification of the lung, more work is still needed to improve the delivery vehicles and to overcome challenges such as entry barriers, persistent expression, specific cell targeting, and circumventing host anti-vector responses.

The solar and equatorial QBO influences on the stratospheric circulation during the early northern-hemisphere winter. [Quasi-Biennial Oscillation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kodera, Kunihiko

1991-06-01

A case study was conducted to investigate the mechanism of how the solar cycle and the equatorial quasi-biennial oscillation (QBO) influence the stratospheric circulation during the Northern-Hemisphere winter. It was found that the solar and QBO influences on the stratospheric jet exist rather independently in the upper stratosphere during December. The mean-zonal wind anomalies produced in early winter persist by deformation until late winter through wave-mean flow interactions with planetary waves. The modulation effect of the solar influence by the QBO takes place during this process.

Postepizootic Persistence of Venezuelan Equine Encephalitis Virus, Venezuela

PubMed Central

Navarro, Juan-Carlos; Medina, Gladys; Vasquez, Clovis; Coffey, Lark L.; Wang, Eryu; Suárez, Alexander; Biord, Hernán; Salas, Marlene

2005-01-01

Five years after the apparent end of the major 1995 Venezuelan equine encephalitis (VEE) epizootic/epidemic, focal outbreaks of equine encephalitis occurred in Carabobo and Barinas States of western Venezuela. Virus isolates from horses in each location were nearly identical in sequence to 1995 isolates, which suggests natural persistence of subtype IC VEE virus (VEEV) strains in a genetically stable mode. Serologic evidence indicated that additional outbreaks occurred in Barinas State in 2003. Field studies identified known Culex (Melanoconion) spp. vectors and reservoir hosts of enzootic VEEV but a dearth of typical epidemic vectors. Cattle serosurveys indicated the recent circulation of enzootic VEEV strains, and possibly of epizootic strains. Persistence of VEEV subtype IC strains and infection of horses at the end of the rainy season suggest the possibility of an alternative, cryptic transmission cycle involving survival through the dry season of infected vectors or persistently infected vertebrates. PMID:16485478

Characterization of increased persistence and intensity of precipitation in the northeastern United States

NASA Astrophysics Data System (ADS)

Guilbert, Justin; Betts, Alan K.; Rizzo, Donna M.; Beckage, Brian; Bomblies, Arne

2015-03-01

We present evidence of increasing persistence in daily precipitation in the northeastern United States that suggests that global circulation changes are affecting regional precipitation patterns. Meteorological data from 222 stations in 10 northeastern states are analyzed using Markov chain parameter estimates to demonstrate that a significant mode of precipitation variability is the persistence of precipitation events. We find that the largest region-wide trend in wet persistence (i.e., the probability of precipitation in 1 day and given precipitation in the preceding day) occurs in June (+0.9% probability per decade over all stations). We also find that the study region is experiencing an increase in the magnitude of high-intensity precipitation events. The largest increases in the 95th percentile of daily precipitation occurred in April with a trend of +0.7 mm/d/decade. We discuss the implications of the observed precipitation signals for watershed hydrology and flood risk.

Correlation of antigenic expression with progress in antibiotic therapy of acute human brucellosis.

PubMed

Kwaasi, A A A; Al-Mohanna, F A; Nakeeb, S M; Roberts, G T; Al-Thawadi, S; Hassan, A Y; Al-Hokail, A; Elfaki, M G

2005-06-01

Human brucellosis is a zoonotic disease which is endemic in Saudi Arabia. The aim of this study was to investigate the humoral immune responses and identify the target antigens that persist at different stages in human brucellosis during antibiotic therapy. To do this, an acute case of accidental nosocomial infection was studied experimentally. Blood was collected from the patient at the time of diagnosis, and at weekly intervals during therapy until remission. IgG and IgM immunoblotting was used to characterize specific antigenic determinants, and ELISA antibody titration was performed to quantify the circulating antibodies. Results indicated that protein bands of 12-13.5 kDa bound IgG in the patient's sera but did not bind IgM on immunoblots and are probably not specific for, or important in, early stage infections. However, an 18 kDa band persisted during infection through remission. The pivotal and most important findings were that the number of protein bands seen on immunoblots, the magnitude of ELISA antibody titres and the concomitant changes in the intensity of the polypeptide bands of 42-43 kDa were positively correlated with the stage of infection. High numbers of anti-IgG and -IgM immunoblot bands coupled with high ELISA antibody titres and a concomitant increase in intensity of the 42-43 kDa bands were positively correlated with acute and severe infection. Conversely, a reduction in the number of polypeptide bands as well as a decrease in the intensity, until the complete disappearance of the 42-43 kDa bands, coupled with low (baseline) ELISA antibody titration values indicated successful treatment and remission. The routine use of the methods described here to ascertain the stage of the disease, assess the progress of antimicrobial therapy and monitor cases of relapse in human brucellosis is suggested.

Imbalanced Oxidative Stress Causes Chlamydial Persistence during Non-Productive Human Herpes Virus Co-Infection

PubMed Central

Prusty, Bhupesh K.; Böhme, Linda; Bergmann, Birgit; Siegl, Christine; Krause, Eva; Mehlitz, Adrian; Rudel, Thomas

2012-01-01

Both human herpes viruses and Chlamydia are highly prevalent in the human population and are detected together in different human disorders. Here, we demonstrate that co-infection with human herpes virus 6 (HHV6) interferes with the developmental cycle of C. trachomatis and induces persistence. Induction of chlamydial persistence by HHV6 is independent of productive virus infection, but requires the interaction and uptake of the virus by the host cell. On the other hand, viral uptake is strongly promoted under co-infection conditions. Host cell glutathione reductase activity was suppressed by HHV6 causing NADPH accumulation, decreased formation of reduced glutathione and increased oxidative stress. Prevention of oxidative stress restored infectivity of Chlamydia after HHV6-induced persistence. We show that co-infection with Herpes simplex virus 1 or human Cytomegalovirus also induces chlamydial persistence by a similar mechanism suggesting that Chlamydia -human herpes virus co-infections are evolutionary shaped interactions with a thus far unrecognized broad significance. PMID:23077614

Comparison of transmission efficiency of different isolates of Potato virus Y among three aphid vectors

USDA-ARS?s Scientific Manuscript database

Potato virus Y (PVY) strains are transmitted by different aphid species in a non-persistent, non-circulative manner. Green peach aphid (GPA, Myzus persicae Sulzer; Aphididae, Macrosiphini) is the most efficient vector in laboratory studies, but potato aphid (PA, Macrosiphum euphorbiae Thomas; Aphidi...

New perspectives on virus detection in shellfish: hemocytes as a source of concentrated virus

USDA-ARS?s Scientific Manuscript database

USDA ARS research indicates that circulating phagocytic cells (hemocytes) within oysters retain virus particles. We find that persistence of hepatitis A virus (HAV) within oyster hemocytes correlates with the presence of virus within whole oysters. Since bivalve shellfish have no self-nonself immun...

High turnover drives prolonged persistence of influenza in managed pig herds

PubMed Central

Aguas, Ricardo; Riley, Steven; Loeffen, Willie L. A.; Wood, James L. N.; Grenfell, Bryan T.

2016-01-01

Pigs have long been hypothesized to play a central role in the emergence of novel human influenza A virus (IAV) strains, by serving as mixing vessels for mammalian and avian variants. However, the key issue of viral persistence in swine populations at different scales is ill understood. We address this gap using epidemiological models calibrated against seroprevalence data from Dutch finishing pigs to estimate the ‘critical herd size’ (CHS) for IAV persistence. We then examine the viral phylogenetic evidence for persistence by comparing human and swine IAV. Models suggest a CHS of approximately 3000 pigs above which influenza was likely to persist, i.e. orders of magnitude lower than persistence thresholds for IAV and other acute viruses in humans. At national and regional scales, we found much stronger empirical signatures of prolonged persistence of IAV in swine compared with human populations. These striking levels of persistence in small populations are driven by the high recruitment rate of susceptible piglets, and have significant implications for management of swine and for overall patterns of genetic diversity of IAV. PMID:27358277

Studies on the liver sequestration of lymphocytes bearing membrane-associated galactose-terminal glycoconjugates: reversal with agents that effectively compete for the asialoglycoprotein receptor.

PubMed

Samlowski, W E; Spangrude, G J; Daynes, R A

1984-10-15

The removal of "effete" glycoproteins from the circulation represents a proposed physiologic role for the hepatocyte asialoglycoprotein receptor. Our experiments support the hypothesis that this receptor may also be directly involved in the removal from the circulation of cells bearing asialoglycoconjugates. We report that the enhanced liver localization of neuraminidase-treated lymphocytes can be competitively inhibited by the coinjection of asialofetuin (ASF). Fetuin itself was without effect. Competitive inhibition of the liver receptor allowed normal localization to lymphoid tissues of the enzyme-treated lymphocytes, a condition which persisted as long as free ASF was present in the circulation. Our studies support the concept that cell surface carbohydrates play an important role in the tissue distribution of circulating lymphocytes. The process of thymocyte maturation, bone marrow transplantation, and the adoptive immunotherapy with continuous T-cell lines represent conditions where recirculation potential may be influenced by the presence of galactose terminal glycoconjugates.

Quercetin transiently increases energy expenditure but persistently decreases circulating markers of inflammation in C57BL/6J mice fed a high-fat diet

PubMed Central

Stewart, Laura K.; Soileau, Jeff L.; Ribnicky, David; Wang, Zhong Q.; Raskin, Ilya; Poulev, Alexander; Majewski, Martin; Cefalu, William T.; Gettys, Thomas W.

2008-01-01

Quercetin, a polyphenolic compound and a major bioflavonoid in the human diet, has anti-inflammatory properties and has been postulated to enhance energy expenditure (EE). We sought to determine whether quercetin alters body weight, body composition, EE, and circulating markers of inflammation. At 6 weeks (W) of age, 2 cohorts of C57BL/6J mice (N = 80) were placed on one of 2 diets for 3W or 8W: (1) high fat (HF) (45% kcal fat) or (2) high fat + quercetin (HF + Q) (45% kcal fat + 0.8% quercetin). Quercetin concentrations in the diet and plasma were evaluated using mass spectrometry. Body weight, composition (nuclear magnetic resonance), and food consumption were measured weekly. Energy expenditure was measured by indirect calorimetry at 3 and 8W, and inflammatory markers were measured in plasma obtained at 8W. The presence of quercetin in the HF diet did not alter food consumption over time in the HF + Q group and did not differ from the HF group at any time point. However, circulating plasma quercetin concentrations declined between 3 and 8W. At 3W, EE was higher during both day and night phases (P < .0001) in the HF + Q group compared with the HF group; but this difference was not detected at 8W and did not translate into significant differences between the HF + Q and HF groups with respect to body weight or body composition. During the night phase, concentrations of the inflammatory markers (interferon-γ, interleukin-1α, and interleukin-4) were significantly lower when compared with HF treatment group (P < .05). Dietary supplementation with quercetin produces transient (3W) increases in EE that are not detected after 8W on the diet. A corresponding decrease in circulating quercetin between 3 and 8W suggests that metabolic adaptation may have diminished the impact of quercetin's early effect on EE and diminished its overall effect on nutrient partitioning and adiposity. However, quercetin at the levels provided was effective in reducing circulating markers of inflammation observed in animals on an HF diet at 8W. PMID:18555853

Out of Africa: a molecular perspective on the introduction of yellow fever virus into the Americas.

PubMed

Bryant, Juliet E; Holmes, Edward C; Barrett, Alan D T

2007-05-18

Yellow fever virus (YFV) remains the cause of severe morbidity and mortality in South America and Africa. To determine the evolutionary history of this important reemerging pathogen, we performed a phylogenetic analysis of the largest YFV data set compiled to date, representing the prM/E gene region from 133 viral isolates sampled from 22 countries over a period of 76 years. We estimate that the currently circulating strains of YFV arose in Africa within the last 1,500 years and emerged in the Americas following the slave trade approximately 300-400 years ago. These viruses then spread westwards across the continent and persist there to this day in the jungles of South America. We therefore illustrate how gene sequence data can be used to test hypotheses of viral dispersal and demographics, and document the role of human migration in the spread of infectious disease.

A 3-year serological and virological cattle follow-up in Madagascar highlands suggests a non-classical transmission route of Rift Valley fever virus.

PubMed

Nicolas, Gaëlle; Durand, Benoit; Rakotoarimanana, Tafika Tojofaniry; Lacote, Sandra; Chevalier, Véronique; Marianneau, Philippe

2014-02-01

Rift Valley fever virus (RVFV) is a mosquito-borne infection of livestock and human which causes a potentially severe disease. In 2008-2009, a RVF outbreak occurred in a temperate and mountainous area located on the highlands of Madagascar. A three-year cattle follow-up (2009-2011) was conducted in a pilot area of this highland. A seroprevalence rate of 28% was estimated in 2009 and a seroconversion rate of 7% in 2009-2010. A third cross-sectional survey showed a seroconversion rate of 14% in 2010-2011. In 2011 the longitudinal study suggested a RVFV circulation during the year. In this area where vectors density is low and cattle exchanges are linked to the virus local spread, we raise hypotheses that may explain the local persistence of the virus.

Out of Africa: A Molecular Perspective on the Introduction of Yellow Fever Virus into the Americas

PubMed Central

Bryant, Juliet E; Holmes, Edward C; Barrett, Alan D. T

2007-01-01

Yellow fever virus (YFV) remains the cause of severe morbidity and mortality in South America and Africa. To determine the evolutionary history of this important reemerging pathogen, we performed a phylogenetic analysis of the largest YFV data set compiled to date, representing the prM/E gene region from 133 viral isolates sampled from 22 countries over a period of 76 years. We estimate that the currently circulating strains of YFV arose in Africa within the last 1,500 years and emerged in the Americas following the slave trade approximately 300–400 years ago. These viruses then spread westwards across the continent and persist there to this day in the jungles of South America. We therefore illustrate how gene sequence data can be used to test hypotheses of viral dispersal and demographics, and document the role of human migration in the spread of infectious disease. PMID:17511518

June 2017: The Earliest European Summer Mega-heatwave of Reanalysis Period

NASA Astrophysics Data System (ADS)

Sánchez-Benítez, A.; García-Herrera, R.; Barriopedro, D.; Sousa, P. M.; Trigo, R. M.

2018-02-01

This paper examines the characteristics of the heatwave that affected western and central Europe in June 2017. Using a novel algorithm, we show that its extension, intensity, and persistence were comparable to those of other European mega-heatwaves, but it occurred earlier in the summer. The most affected area was Iberia, which experienced devastating forest fires with human casualties and the warmest temperatures of the reanalysis period from daily to seasonal scales. The peak of the mega-heatwave displayed an unprecedented warm air intrusion due to a record-breaking subtropical ridge with signatures closer to those of July and August. The atmospheric circulation was the main triggering factor of the event. However, thermodynamical changes of the last decades made a substantial contribution to the event, by increasing the likelihood of surpassing high-temperature thresholds. This episode could be a good example of a coming future, with high-summer mega-heatwaves occurring earlier.

Poultry raising systems and highly pathogenic avian influenza outbreaks in Thailand: the situation, associations, and impacts.

PubMed

Chantong, Wasan; Kaneene, John B

2011-05-01

Highly pathogenic avian influenza (HPAI), caused by the virus strain H5N1, currently occurs worldwide with the greatest burden in Southeast Asia where the disease was first reported. In Thailand where the disease was first confirmed in January 2004, the virus had been persistent as a major threat to the poultry industry and human health over the past several years. It was generally hypothesized that the main reason for the disease to circulate in Thailand was the existence of traditional backyard chickens and free-range ducks raising systems. Consequently, this study reviewed the structure of poultry raising systems, the recent outbreaks of HPAI H5N1, the disease association to the backyard and free-grazing poultry production, and consequences of the outbreaks in Thailand. Although the major outbreaks in the country had declined, the sustaining disease surveillance and prevention are still strongly recommended.

Antibody localization in the glomerular basement membrane may precede in situ immune deposit formation in rat glomeruli.

PubMed

Agodoa, L Y; Gauthier, V J; Mannik, M

1985-02-01

The administration of cationized antibodies, specific to human serum albumin, into the renal artery of rats caused transient presence of IgG in glomeruli by immunofluorescence microscopy. Intravenous infusion of appropriate doses of antigen after the injection of cationized antibodies resulted in immune deposit formation in glomeruli that persisted through 96 hr. By electron microscopy, these deposits were located in the subepithelial area. The injection of large doses of antigen produced immune deposits which were present in glomeruli for only a few hours, presumably due to formation of only small-latticed immune complexes. The presented data indicate that cationic antibodies bound to the fixed negative charges of the glomerular basement membrane can interact with circulating antigen to form immune deposits in glomeruli. This mechanism may be important because anionic antigens have been shown to induce the synthesis of cationic antibodies.

Experimental 'jet lag' inhibits adult neurogenesis and produces long-term cognitive deficits in female hamsters.

PubMed

Gibson, Erin M; Wang, Connie; Tjho, Stephanie; Khattar, Neera; Kriegsfeld, Lance J

2010-12-01

Circadian disruptions through frequent transmeridian travel, rotating shift work, and poor sleep hygiene are associated with an array of physical and mental health maladies, including marked deficits in human cognitive function. Despite anecdotal and correlational reports suggesting a negative impact of circadian disruptions on brain function, this possibility has not been experimentally examined. In the present study, we investigated whether experimental 'jet lag' (i.e., phase advances of the light:dark cycle) negatively impacts learning and memory and whether any deficits observed are associated with reductions in hippocampal cell proliferation and neurogenesis. Because insults to circadian timing alter circulating glucocorticoid and sex steroid concentrations, both of which influence neurogenesis and learning/memory, we assessed the contribution of these endocrine factors to any observed alterations. Circadian disruption resulted in pronounced deficits in learning and memory paralleled by marked reductions in hippocampal cell proliferation and neurogenesis. Significantly, deficits in hippocampal-dependent learning and memory were not only seen during the period of the circadian disruption, but also persisted well after the cessation of jet lag, suggesting long-lasting negative consequences on brain function. Together, these findings support the view that circadian disruptions suppress hippocampal neurogenesis via a glucocorticoid-independent mechanism, imposing pronounced and persistent impairments on learning and memory.

Antarctic-Wide Array of High-Resolution Ice Core Records Reveals Pervasive Lead Pollution Began in 1889 and Persists Today

NASA Technical Reports Server (NTRS)

McConnell, J. R.; Maselli, O. J.; Sigl, M.; Vallelonga, P.; Neumann, Thomas Allen; Anschutz, H.; Bales, R. C.; Curran, M. A. J.; Das, S. B.; Edwards, R.;

Right Ventricular Failure Post LVAD Implantation Corrected with Biventricular Support: An In Vitro Model.

PubMed

Shehab, Sajad; Allida, Sabine M; Davidson, Patricia M; Newton, Phillip J; Robson, Desiree; Jansz, Paul C; Hayward, Christopher S

Right ventricular failure after left ventricular assist device (LVAD) implantation is associated with high mortality. Management remains limited to pharmacologic therapy and temporary mechanical support. Delayed right ventricular assist device (RVAD) support after LVAD implantation is associated with poorer outcomes. With the advent of miniaturized, durable, continuous flow ventricular assist device systems, chronic RVAD and biventricular assist device (BiVAD) support has been used with some success. The purpose of this study was to assess combined BiVAD and LVAD with delayed RVAD support within a four-elemental mock circulatory loop (MCL) simulating the human cardiovascular system. Our hypothesis was that delayed continuous flow RVAD (RVAD) would produce similar hemodynamic and flow parameters to those of initial BiVAD support. Using the MCL, baseline biventricular heart failure with elevated right and left filling pressures with low cardiac output was simulated. The addition of LVAD within a biventricular configuration improved cardiac output somewhat, but was associated with persistent right heart failure with elevated right-sided filling pressures. The addition of an RVAD significantly improved LVAD outputs and returned filling pressures to normal throughout the circulation. In conclusion, RVAD support successfully restored hemodynamics and flow parameters of biventricular failure supported with isolated LVAD with persistent elevated right atrial pressure.

Antarctic-wide array of high-resolution ice core records reveals pervasive lead pollution began in 1889 and persists today.

PubMed

McConnell, J R; Maselli, O J; Sigl, M; Vallelonga, P; Neumann, T; Anschütz, H; Bales, R C; Curran, M A J; Das, S B; Edwards, R; Kipfstuhl, S; Layman, L; Thomas, E R

2014-07-28

Interior Antarctica is among the most remote places on Earth and was thought to be beyond the reach of human impacts when Amundsen and Scott raced to the South Pole in 1911. Here we show detailed measurements from an extensive array of 16 ice cores quantifying substantial toxic heavy metal lead pollution at South Pole and throughout Antarctica by 1889 - beating polar explorers by more than 22 years. Unlike the Arctic where lead pollution peaked in the 1970s, lead pollution in Antarctica was as high in the early 20(th) century as at any time since industrialization. The similar timing and magnitude of changes in lead deposition across Antarctica, as well as the characteristic isotopic signature of Broken Hill lead found throughout the continent, suggest that this single emission source in southern Australia was responsible for the introduction of lead pollution into Antarctica at the end of the 19(th) century and remains a significant source today. An estimated 660 t of industrial lead have been deposited over Antarctica during the past 130 years as a result of mid-latitude industrial emissions, with regional-to-global scale circulation likely modulating aerosol concentrations. Despite abatement efforts, significant lead pollution in Antarctica persists into the 21(st) century.

Antarctic-wide array of high-resolution ice core records reveals pervasive lead pollution began in 1889 and persists today

PubMed Central

McConnell, J. R.; Maselli, O. J.; Sigl, M.; Vallelonga, P.; Neumann, T.; Anschütz, H.; Bales, R. C.; Curran, M. A. J.; Das, S. B.; Edwards, R.; Kipfstuhl, S.; Layman, L.; Thomas, E. R.

2014-01-01

Interior Antarctica is among the most remote places on Earth and was thought to be beyond the reach of human impacts when Amundsen and Scott raced to the South Pole in 1911. Here we show detailed measurements from an extensive array of 16 ice cores quantifying substantial toxic heavy metal lead pollution at South Pole and throughout Antarctica by 1889 – beating polar explorers by more than 22 years. Unlike the Arctic where lead pollution peaked in the 1970s, lead pollution in Antarctica was as high in the early 20th century as at any time since industrialization. The similar timing and magnitude of changes in lead deposition across Antarctica, as well as the characteristic isotopic signature of Broken Hill lead found throughout the continent, suggest that this single emission source in southern Australia was responsible for the introduction of lead pollution into Antarctica at the end of the 19th century and remains a significant source today. An estimated 660 t of industrial lead have been deposited over Antarctica during the past 130 years as a result of mid-latitude industrial emissions, with regional-to-global scale circulation likely modulating aerosol concentrations. Despite abatement efforts, significant lead pollution in Antarctica persists into the 21st century. PMID:25068819

Assessment of Chlamydia psittaci Shedding and Environmental Contamination as Potential Sources of Worker Exposure throughout the Mule Duck Breeding Process

PubMed Central

Hulin, V.; Bernard, P.; Vorimore, F.; Aaziz, R.; Cléva, D.; Robineau, J.; Durand, B.; Angelis, L.

2015-01-01

Chlamydia psittaci is an obligate intracellular bacterium responsible for avian chlamydiosis, otherwise known as psittacosis, a zoonotic disease that may lead to severe atypical pneumonia. This study was conducted on seven mule duck flocks harboring asymptomatic birds to explore the circulation and persistence of C. psittaci during the entire breeding process and assess the potential sources of worker exposure. Cloacal swabs and air samples were taken on each occasion requiring humans to handle the birds. In parallel, environmental samples, including dust, water, and soil, were collected. Specific real-time PCR analyses revealed the presence of C. psittaci in all flocks but with three different shedding patterns involving ducks about the age of 4, 8, and 12 weeks with heavy, moderate, and low excretion levels, respectively. Air samples were only positive in flocks harboring heavy shedders. Dust in flocks with heavy or moderate shedders carried chlamydial loads strongly associated with the loads detected in avian and soil samples. Environmental contamination, significantly correlated with shedding dynamics, was considered to be the most probable source of exposure. The high prevalence of bacteriophage Chp1 in all flocks, mostly jointly present with chlamydia, suggests an important factor in C. psittaci persistence, thus creating a greater risk for humans. A survey conducted in these flocks regarding farming practices and activities showed that disinfection seems to be the most promising practice for reducing C. psittaci prevalence in ducks and that the place and the duration of action during operations seem to be potential risk factors. Strict adherence to good practices is strongly recommended. PMID:26712548

Extreme premature with persistent left superior vena cava.

PubMed

Aboitiz-Rivera, Carlos Manuel; Blachman-Braun, Ruben; Parra-Pérez, Mariana Yazmin

2017-10-01

Persistent left superior vena cava (PLSVC) is a congenital anomaly, that results when there is an absence of the normal regression of the left common precardinal vein during embryogenesis. Usually, this anomaly remains asymptomatic, however, when the PLSVC drains into the left atrium this could lead to a right-to-left shunt. Additionally, this can result in inadvertent delivery of air or thrombus into the systemic circulation with potential neurologic, cardiac and renal complications. In this article, we present a case of an extreme premature Mexican newborn in which the diagnosis was made after placement of a percutaneous central venues catheter.

Redox Signaling and Persistent Pulmonary Hypertension of the Newborn.

PubMed

Sharma, Megha; Afolayan, Adeleye J

2017-01-01

Reactive oxygen species (ROS) are redox-signaling molecules that are critically involved in regulating endothelial cell functions, host defense, aging, and cellular adaptation. Mitochondria are the major sources of ROS and important sources of redox signaling in pulmonary circulation. It is becoming increasingly evident that increased mitochondrial oxidative stress and aberrant signaling through redox-sensitive pathways play a direct causative role in the pathogenesis of many cardiopulmonary disorders including persistent pulmonary hypertension of the newborn (PPHN). This chapter highlights redox signaling in endothelial cells, antioxidant defense mechanism, cell responses to oxidative stress, and their contributions to disease pathogenesis.

T-cell homeostasis in breast cancer survivors with persistent fatigue.

PubMed

Bower, Julienne E; Ganz, Patricia A; Aziz, Najib; Fahey, John L; Cole, Steve W

2003-08-06

Approximately 30% of women successfully treated for breast cancer suffer persistent fatigue of unknown origin. Recent studies linking inflammatory processes to central nervous system-mediated fatigue led us to examine cellular immune system status in 20 fatigued breast cancer survivors and 19 matched non-fatigued breast cancer survivors. Fatigued survivors, compared with non-fatigued survivors, had statistically significantly increased numbers of circulating T lymphocytes (mean 31% increase, 95% confidence interval [CI] = 6% to 56%; P =.015 by two-sided analysis of variance [ANOVA]), with pronounced elevation in the numbers of CD4+ T lymphocytes (mean 41% increase, 95% CI = 15% to 68%; P =.003 by two-sided ANOVA) and CD56+ effector T lymphocytes (mean 52% increase, 95% CI = 4% to 99%; P =.027 by two-sided ANOVA). These changes were independent of patient demographic and treatment characteristics. Absolute numbers of B cells, natural killer cells, granulocytes, and monocytes were not altered. The increased numbers of circulating T cells correlated with elevations in the level of serum interleukin 1 receptor antagonist (for CD3+ cells, r =.56 and P =.001; for CD3+/CD4+ cells, r =.68 and P<.001, by Spearman rank correlation). Results of this study suggest that persistent fatigue in breast cancer survivors might be associated with a chronic inflammatory process involving the T-cell compartment. These results require confirmation in a larger study that is specifically designed to address this hypothesis.

Antigenicity of the 2015-2016 seasonal H1N1 human influenza virus HA and NA proteins.

PubMed

Clark, Amelia M; DeDiego, Marta L; Anderson, Christopher S; Wang, Jiong; Yang, Hongmei; Nogales, Aitor; Martinez-Sobrido, Luis; Zand, Martin S; Sangster, Mark Y; Topham, David J

2017-01-01

Antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) influenza virus proteins contributes to reduced vaccine efficacy. To analyze antigenic drift in human seasonal H1N1 viruses derived from the 2009 pandemic H1N1 virus (pH1N1-like viruses) accounts for the limited effectiveness (around 40%) of vaccination against pH1N1-like viruses during the 2015-2016 season, nasal washes/swabs collected from adult subjects in the Rochester, NY area, were used to sequence and isolate the circulating viruses. The HA and NA proteins from viruses circulating during the 2015-2016 season encoded eighteen and fourteen amino acid differences, respectively, when compared to A/California/04/2009, a strain circulating at the origin of the 2009 pandemic. The circulating strains belonged to subclade 6B.1, defined by HA amino acid substitutions S101N, S179N, and I233T. Hemagglutination-inhibiting (HAI) and HA-specific neutralizing serum antibody (Ab) titers from around 50% of pH1N1-like virus-infected subjects and immune ferrets were 2-4 fold lower for the 2015-2016 circulating strains compared to the vaccine strain. In addition, using a luminex-based mPlex HA assay, the binding of human sera from subjects infected with pH1N1-like viruses to the HA proteins from circulating and vaccine strains was not identical, strongly suggesting antigenic differences in the HA protein. Additionally, NA inhibition (NAI) Ab titers in human sera from pH1N1-like virus-infected subjects increased after the infection and there were measurable antigenic differences between the NA protein of circulating strains and the vaccine strain using both ferret and human antisera. Despite having been vaccinated, infected subjects exhibited low HAI Ab titers against the vaccine and circulating strains. This suggests that poor responses to the H1N1 component of the vaccine as well as antigenic differences in the HA and NA proteins of currently circulating pH1N1-like viruses could be contributing to risk of infection even after vaccination.

Antigenicity of the 2015–2016 seasonal H1N1 human influenza virus HA and NA proteins

PubMed Central

Anderson, Christopher S.; Wang, Jiong; Yang, Hongmei; Nogales, Aitor; Martinez-Sobrido, Luis; Zand, Martin S.; Sangster, Mark Y.; Topham, David J.

2017-01-01

Antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) influenza virus proteins contributes to reduced vaccine efficacy. To analyze antigenic drift in human seasonal H1N1 viruses derived from the 2009 pandemic H1N1 virus (pH1N1-like viruses) accounts for the limited effectiveness (around 40%) of vaccination against pH1N1-like viruses during the 2015–2016 season, nasal washes/swabs collected from adult subjects in the Rochester, NY area, were used to sequence and isolate the circulating viruses. The HA and NA proteins from viruses circulating during the 2015–2016 season encoded eighteen and fourteen amino acid differences, respectively, when compared to A/California/04/2009, a strain circulating at the origin of the 2009 pandemic. The circulating strains belonged to subclade 6B.1, defined by HA amino acid substitutions S101N, S179N, and I233T. Hemagglutination-inhibiting (HAI) and HA-specific neutralizing serum antibody (Ab) titers from around 50% of pH1N1-like virus-infected subjects and immune ferrets were 2–4 fold lower for the 2015–2016 circulating strains compared to the vaccine strain. In addition, using a luminex-based mPlex HA assay, the binding of human sera from subjects infected with pH1N1-like viruses to the HA proteins from circulating and vaccine strains was not identical, strongly suggesting antigenic differences in the HA protein. Additionally, NA inhibition (NAI) Ab titers in human sera from pH1N1-like virus-infected subjects increased after the infection and there were measurable antigenic differences between the NA protein of circulating strains and the vaccine strain using both ferret and human antisera. Despite having been vaccinated, infected subjects exhibited low HAI Ab titers against the vaccine and circulating strains. This suggests that poor responses to the H1N1 component of the vaccine as well as antigenic differences in the HA and NA proteins of currently circulating pH1N1-like viruses could be contributing to risk of infection even after vaccination. PMID:29145498

Circulating anti-double-stranded DNA antibody-secreting cells in patients with systemic lupus erythematosus: a novel biomarker for disease activity.

PubMed

Hanaoka, H; Okazaki, Y; Satoh, T; Kaneko, Y; Yasuoka, H; Seta, N; Kuwana, M

2012-10-01

Antibodies against double-stranded DNA (dsDNA) are widely used to diagnose systemic lupus erythematosus (SLE) and evaluate its activity in patients. This study was undertaken to examine the clinical utility of circulating anti-dsDNA antibody-secreting cells for evaluating SLE patients. Anti-dsDNA antibody-secreting cells quantified using an enzyme-linked immunospot assay were detected in the spleen, bone marrow and peripheral blood from MRL/lpr but not in control BALB/c mice. Circulating anti-dsDNA antibody-secreting cells were detected in 29 (22%) of 130 patients with SLE, but in none of 49 with non-SLE connective-tissue disease or 18 healthy controls. The presence of circulating anti-dsDNA antibody-secreting cells was associated with persistent proteinuria, high SLE disease activity index and systemic lupus activity measures, and a high serum anti-dsDNA antibody titre measured with an enzyme-linked immunosorbent assay. The positive predictive value for active disease was 48% for circulating anti-dsDNA antibody-secreting cells versus 17% for serum anti-dsDNA antibodies. A prospective cohort of patients with circulating anti-dsDNA antibodies and inactive SLE showed that the cumulative disease flare-free rate was significantly lower in patients with than without circulating anti-dsDNA antibody-secreting cells (p < 0.001). Circulating anti-dsDNA antibody-secreting cells are a useful biomarker for assessing disease activity in SLE patients.

Spatial stabilization and intensification of moistening and drying rate patterns under future climate change

NASA Astrophysics Data System (ADS)

Chavaillaz, Yann; Joussaume, Sylvie; Bony, Sandrine; Braconnot, Pascale

2016-08-01

Precipitation projections are usually presented as the change in precipitation between a fixed current baseline and a particular time in the future. However, upcoming generations will be affected in a way probably more related to the moving trend in precipitation patterns, i.e. to the rate and the persistence of regional precipitation changes from one generation to the next, than to changes relative to a fixed current baseline. In this perspective, we propose an alternative characterization of the future precipitation changes predicted by general circulation models, focusing on the precipitation difference between two subsequent 20-year periods. We show that in a business-as-usual emission pathway, the moistening and drying rates increase by 30-40 %, both over land and ocean. As we move further over the twenty-first century, more regions exhibit a significant rate of precipitation change, while the patterns become geographically stationary and the trends persistent. The stabilization of the geographical rate patterns that occurs despite the acceleration of global warming can be physically explained: it results from the increasing contribution of thermodynamic processes compared to dynamic processes in the control of precipitation change. We show that such an evolution is already noticeable over the last decades, and that it could be reversed if strong mitigation policies were quickly implemented. The combination of intensification and increasing persistence of precipitation rate patterns may affect the way human societies and natural ecosystems adapt to climate change, especially in the Mediterranean basin, in Central America, in South Asia and in the Arctic.

Infection of the whitefly Bemisia tabaci with Rickettsia spp. alters its interactions with Tomato yellow leaf curl virus

USDA-ARS?s Scientific Manuscript database

Numerous animal and plant viruses are transmitted by arthropod vectors in a persistent, circulative manner. Tomato yellow leaf curl virus (TYLCV) is transmitted by the sweet potato whitefly Bemisia tabaci. Here we report that infection with Rickettsia spp., a facultative endosymbiont of whiteflies...

The Call to Critique "Common Sense" Understandings about Boys and Masculinity(ies)

ERIC Educational Resources Information Center

Dalley-Trim, Leanne

2009-01-01

This paper is founded upon the premise that "common sense" understandings about boys persist within schools and, given this continuing circulation of such understandings, advocates the need to critique such conceptualising. It does so on the grounds that such understandings, and the essentialist discursive knowledges informing these, fail to take…

[The use of low-frequency magnetotherapy and EHF puncture in the combined treatment of arterial hypertension in vibration-induced disease].

PubMed

Drobyshev, V A; Filippova, G N; Loseva, M I; Shpagina, L A; Shelepova, N V; Zhelezniak, M S

2000-01-01

Combination of EHF therapy + magnetotherapy + drugs results in faster and persistent hypotensive and analgetic effect compared to standard drug therapy, potentiates action of vascular drugs on cerebral and peripheral circulation, reduces dose of hypotensive drugs in patients with arterial hypertension and vibration disease.

231Pa/230Th evidence for a weakened but persistent Atlantic meridional overturning circulation during Heinrich Stadial 1.

PubMed

Bradtmiller, Louisa I; McManus, Jerry F; Robinson, Laura F

2014-12-18

The strength of Atlantic meridional overturning circulation is believed to affect the climate over glacial-interglacial and millennial timescales. The marine sedimentary (231)Pa/(230)Th ratio is a promising paleocirculation proxy, but local particle effects may bias individual reconstructions. Here we present new Atlantic sedimentary (231)Pa/(230)Th data from the Holocene, the last glacial maximum and Heinrich Stadial 1, a period of abrupt cooling ca. 17,500 years ago. We combine our results with published data from these intervals to create a spatially distributed sedimentary (231)Pa/(230)Th database. The data reveal a net (231)Pa deficit during each period, consistent with persistent (231)Pa export. In highly resolved cores, Heinrich (231)Pa/(230)Th ratios exceed glacial ratios at nearly all depths, indicating a significant reduction, although not cessation, of overturning during Heinrich Stadial 1. These results support the inference that weakened overturning was a driver of Heinrich cooling, while suggesting that abrupt climate oscillations do not necessarily require a complete shutdown of overturning.

Mie lidar and radiosonde observations at Gadanki (13.5°N, 79.2°E) during sudden stratospheric warming of 2009

NASA Astrophysics Data System (ADS)

Sridharan, S.; Raghunath, K.; Sathishkumar, S.; Nath, D.

2011-03-01

During a major sudden stratospheric warming event (21-27 January 2009), Mie-lidar observations at Gadanki (13.5°N, 79.2°E) show persistent occurrence of cirrus clouds. Outgoing long-wave radiation averaged for 70°E-90°E, decreases to a low value (170 W/m2) on 27 January 2009 over equator indicating deep convection. The zonal mean ERA-Interim data reveal large northward and upward circulation over equatorial upper troposphere. The latitude-longitude map of ERA-Interim zonal mean potential vorticity (PV) indicates two tongues of high PV emanating from polar latitudes and extending further down to equator. Radiosonde observations at Gadanki show the presence of ∼40% relative humidity at 11-13 km and lower tropopause temperature. It is inferred that the tropical circulation change due to PV intrusion leads to deep convection, which along with high humidity and low tropopause temperature leading to the formation of persistent cirrus clouds, the occurrence frequency of which is normally less during winter season over Gadanki.

Persistence: A Key Factor in Human Performance at Work.

ERIC Educational Resources Information Center

Blair, Daniel V.; Price, Donna J.

1998-01-01

Reviews the construct of persistence as it relates to achievement motivation at work. Topics include foundational concepts of persistence; achievement motivation theory; a human motivation model; goal-setting theory; self-efficacy theory; expectancy theory; task assignments; confidence; and perceived value. (LRW)

[The present and future state of minimized extracorporeal circulation].

PubMed

Meng, Fan; Yang, Ming

2013-05-01

Minimized extracorporeal circulation improved in the postoperative side effects of conventional extracorporeal circulation is a kind of new extracorporeal circulation. This paper introduces the principle, characteristics, applications and related research of minimized extracorporeal circulation. For the problems of systemic inflammatory response syndrome and limited assist time, the article proposes three development direction including system miniaturization and integration, pulsatile blood pump and the adaptive control by human parameter identification.

Persistently active neurons in human medial frontal and medial temporal lobe support working memory

PubMed Central

Kamiński, J; Sullivan, S; Chung, JM; Ross, IB; Mamelak, AN; Rutishauser, U

2017-01-01

Persistent neural activity is a putative mechanism for the maintenance of working memories. Persistent activity relies on the activity of a distributed network of areas, but the differential contribution of each area remains unclear. We recorded single neurons in the human medial frontal cortex and the medial temporal lobe while subjects held up to three items in memory. We found persistently active neurons in both areas. Persistent activity of hippocampal and amygdala neurons was stimulus-specific, formed stable attractors, and was predictive of memory content. Medial frontal cortex persistent activity, on the other hand, was modulated by memory load and task set but was not stimulus-specific. Trial-by-trial variability in persistent activity in both areas was related to memory strength, because it predicted the speed and accuracy by which stimuli were remembered. This work reveals, in humans, direct evidence for a distributed network of persistently active neurons supporting working memory maintenance. PMID:28218914

Effects of HIV infection and ART on phenotype and function of circulating monocytes, natural killer, and innate lymphoid cells.

PubMed

Nabatanzi, Rose; Cose, Stephen; Joloba, Moses; Jones, Sarah Rowland; Nakanjako, Damalie

2018-03-15

HIV infection causes upregulation of markers of inflammation, immune activation and apoptosis of host adaptive, and innate immune cells particularly monocytes, natural killer (NK) and innate lymphoid cells (ILCs). Although antiretroviral therapy (ART) restores CD4 T-cell counts, the persistent aberrant activation of monocytes, NK and ILCs observed likely contributes to the incomplete recovery of T-cell effector functions. A better understanding of the effects of HIV infection and ART on the phenotype and function of circulating monocytes, NK, and ILCs is required to guide development of novel therapeutic interventions to optimize immune recovery.

Chlamydia trachomatis Infection and Anti-Hsp60 Immunity: The Two Sides of the Coin

PubMed Central

Cappello, Francesco; Conway de Macario, Everly; Di Felice, Valentina; Zummo, Giovanni; Macario, Alberto J. L.

2009-01-01

Chlamydia trachomatis (CT) infection is one of the most common causes of reproductive tract diseases and infertility. CT-Hsp60 is synthesized during infection and is released in the bloodstream. As a consequence, immune cells will produce anti-CT-Hsp60 antibodies. Hsp60, a ubiquitous and evolutionarily conserved chaperonin, is normally sequestered inside the cell, particularly into mitochondria. However, upon cell stress, as well as during carcinogenesis, the chaperonin becomes exposed on the cell surface (sf-Hsp60) and/or is secreted from cells into the extracellular space and circulation. Reports in the literature on circulating Hsp and anti-Hsp antibodies are in many cases short on details about Hsp60 concentrations, and about the specificity spectra of the antibodies, their titers, and their true, direct, pathogenetic effects. Thus, more studies are still needed to obtain a definitive picture on these matters. Nevertheless, the information already available indicates that the concurrence of persistent CT infection and appearance of sf-Hsp60 can promote an autoimmune aggression towards stressed cells and the development of diseases such as autoimmune arthritis, multiple sclerosis, atherosclerosis, vasculitis, diabetes, and thyroiditis, among others. At the same time, immunocomplexes composed of anti-CT-Hsp60 antibodies and circulating Hsp60 (both CT and human) may form deposits in several anatomical locations, e.g., at the glomerular basal membrane. The opposite side of the coin is that pre-tumor and tumor cells with sf-Hsp60 can be destroyed with participation of the anti-Hsp60 antibody, thus stopping cancer progression before it is even noticed by the patient or physician. PMID:19714222

Circulating Cell-free DNA for Metastatic Cervical Cancer Detection, Genotyping, and Monitoring.

PubMed

Kang, Zhigang; Stevanović, Sanja; Hinrichs, Christian S; Cao, Liang

2017-11-15

Purpose: Circulating cell-free (ccf) human papillomavirus (HPV) DNA may serve as a unique tumor marker for HPV-associated malignancies, including cervical cancer. We developed a method to genotype and quantify circulating HPV DNA in patients with HPV16- or HPV18-positive metastatic cervical cancer for potential disease monitoring and treatment-related decision making. Experimental Design: In this retrospective study, HPV ccfDNA was measured in serum samples from 19 metastatic cervical cancer patients by duplex digital droplet PCR (ddPCR). Nine patients had received tumor-infiltrating lymphocyte (TIL) immunotherapy. ccfDNA data were aligned with the tumor HPV genotype, drug treatment, and clinical outcome. Results: In blinded tests, HPV ccfDNA was detected in 19 of 19 (100%) patients with HPV-positive metastatic cervical cancer but not in any of the 45 healthy blood donors. The HPV genotype harbored in the patients' tumors was correctly identified in 87 of 87 (100%) sequential patient serum samples from 9 patients who received TIL immunotherapy. In three patients who experienced objective cancer regression after TIL treatment, a transient HPV ccfDNA peak was detected 2-3 days after TIL infusion. Furthermore, persistent clearance of HPV ccfDNA was only observed in two patients who experienced complete response (CR) after TIL immunotherapy. Conclusions: HPV ccfDNA represents a promising tumor marker for noninvasive HPV genotyping and may be used in selecting patients for HPV type-specific T-cell-based immunotherapies. It may also have value in detecting antitumor activity of therapeutic agents and in the long-term follow-up of cervical cancer patients in remission. Clin Cancer Res; 23(22); 6856-62. ©2017 AACR . ©2017 American Association for Cancer Research.

Potential predictability and forecast skill in ensemble climate forecast: the skill-persistence rule

NASA Astrophysics Data System (ADS)

Jin, Y.; Rong, X.; Liu, Z.

2017-12-01

This study investigates the factors that impact the forecast skill for the real world (actual skill) and perfect model (perfect skill) in ensemble climate model forecast with a series of fully coupled general circulation model forecast experiments. It is found that the actual skill of sea surface temperature (SST) in seasonal forecast is substantially higher than the perfect skill on a large part of the tropical oceans, especially the tropical Indian Ocean and the central-eastern Pacific Ocean. The higher actual skill is found to be related to the higher observational SST persistence, suggesting a skill-persistence rule: a higher SST persistence in the real world than in the model could overwhelm the model bias to produce a higher forecast skill for the real world than for the perfect model. The relation between forecast skill and persistence is further examined using a first-order autoregressive model (AR1) analytically for theoretical solutions and numerically for analogue experiments. The AR1 model study shows that the skill-persistence rule is strictly valid in the case of infinite ensemble size, but can be distorted by the sampling error and non-AR1 processes.

Plasmodium vivax: modern strategies to study a persistent parasite's life cycle.

PubMed

Galinski, Mary R; Meyer, Esmeralda V S; Barnwell, John W

2013-01-01

Plasmodium vivax has unique attributes to support its survival in varying ecologies and climates. These include hypnozoite forms in the liver, an invasion preference for reticulocytes, caveola-vesicle complex structures in the infected erythrocyte membrane and rapidly forming and circulating gametocytes. These characteristics make this species very different from P. falciparum. Plasmodium cynomolgi and other related simian species have identical biology and can serve as informative models of P. vivax infections. Plasmodium vivax and its model parasites can be grown in non-human primates (NHP), and in short-term ex vivo cultures. For P. vivax, in the absence of in vitro culture systems, these models remain highly relevant side by side with human clinical studies. While post-genomic technologies allow for greater exploration of P. vivax-infected blood samples from humans, these come with restrictions. Two advantages of NHP models are that infections can be experimentally tailored to address hypotheses, including genetic manipulation. Also, systems biology approaches can capitalise on computational biology combined with set experimental infection periods and protocols, which may include multiple sampling times, different types of samples, and the broad use of "omics" technologies. Opportunities for research on vivax malaria are increasing with the use of existing and new methodological strategies in combination with modern technologies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Equatorial Indian Ocean subsurface current variability in an Ocean General Circulation Model

NASA Astrophysics Data System (ADS)

Gnanaseelan, C.; Deshpande, Aditi

2018-03-01

The variability of subsurface currents in the equatorial Indian Ocean is studied using high resolution Ocean General Circulation Model (OGCM) simulations during 1958-2009. February-March eastward equatorial subsurface current (ESC) shows weak variability whereas strong variability is observed in northern summer and fall ESC. An eastward subsurface current with maximum amplitude in the pycnocline is prominent right from summer to winter during strong Indian Ocean Dipole (IOD) years when air-sea coupling is significant. On the other hand during weak IOD years, both the air-sea coupling and the ESC are weak. This strongly suggests the role of ESC on the strength of IOD. The extension of the ESC to the summer months during the strong IOD years strengthens the oceanic response and supports intensification and maintenance of IODs through modulation of air sea coupling. Although the ESC is triggered by equatorial winds, the coupled air-sea interaction associated with IODs strengthens the ESC to persist for several seasons thereby establishing a positive feedback cycle with the surface. This suggests that the ESC plays a significant role in the coupled processes associated with the evolution and intensification of IOD events by cooling the eastern basin and strengthening thermocline-SST (sea surface temperature) interaction. As the impact of IOD events on Indian summer monsoon is significant only during strong IOD years, understanding and monitoring the evolution of ESC during these years is important for summer monsoon forecasting purposes. There is a westward phase propagation of anomalous subsurface currents which persists for a year during strong IOD years, whereas such persistence or phase propagation is not seen during weak IOD years, supporting the close association between ESC and strength of air sea coupling during strong IOD years. In this study we report the processes which strengthen the IOD events and the air sea coupling associated with IOD. It also unravels the connection between equatorial Indian Ocean circulation and evolution and strengthening of IOD.

Subtyping Salmonella enterica serovar enteritidis isolates from different sources by using sequence typing based on virulence genes and clustered regularly interspaced short palindromic repeats (CRISPRs).

PubMed

Liu, Fenyun; Kariyawasam, Subhashinie; Jayarao, Bhushan M; Barrangou, Rodolphe; Gerner-Smidt, Peter; Ribot, Efrain M; Knabel, Stephen J; Dudley, Edward G

2011-07-01

Salmonella enterica subsp. enterica serovar Enteritidis is a major cause of food-borne salmonellosis in the United States. Two major food vehicles for S. Enteritidis are contaminated eggs and chicken meat. Improved subtyping methods are needed to accurately track specific strains of S. Enteritidis related to human salmonellosis throughout the chicken and egg food system. A sequence typing scheme based on virulence genes (fimH and sseL) and clustered regularly interspaced short palindromic repeats (CRISPRs)-CRISPR-including multi-virulence-locus sequence typing (designated CRISPR-MVLST)-was used to characterize 35 human clinical isolates, 46 chicken isolates, 24 egg isolates, and 63 hen house environment isolates of S. Enteritidis. A total of 27 sequence types (STs) were identified among the 167 isolates. CRISPR-MVLST identified three persistent and predominate STs circulating among U.S. human clinical isolates and chicken, egg, and hen house environmental isolates in Pennsylvania, and an ST that was found only in eggs and humans. It also identified a potential environment-specific sequence type. Moreover, cluster analysis based on fimH and sseL identified a number of clusters, of which several were found in more than one outbreak, as well as 11 singletons. Further research is needed to determine if CRISPR-MVLST might help identify the ecological origins of S. Enteritidis strains that contaminate chickens and eggs.

T cell receptor αβ diversity inversely correlates with pathogen-specific antibody levels in human cytomegalovirus infection.

PubMed

Wang, George C; Dash, Pradyot; McCullers, Jonathan A; Doherty, Peter C; Thomas, Paul G

2012-04-04

A diverse T cell receptor (TCR) repertoire capable of recognizing a broad range of antigenic peptides is thought to be central to effective pathogen-specific immunity by counteracting escape mutations, selecting high-avidity T cells, and providing T cell specificities with comprehensive functional characteristics. However, evidence that TCR diversity is important for the successful control of human infections is limited. A single-cell strategy for the clonotypic analysis of human CD8⁺ TCRαβ repertoires was used to probe the diversity and magnitude of individual human cytomegalovirus (CMV)-specific CD8⁺ T cells recovered directly ex vivo. We found that CD8⁺ TCRαβ repertoire diversity, but not the size of the CD8⁺ T cell response, was inversely related to circulating CMV-specific antibody levels, a measure that has been correlated epidemiologically with differential mortality risks and found here to be higher in persons with detectable (versus undetectable) CMV viral loads. Overall, our findings indicate that CD8⁺ T cell diversity may be more important than T cell abundance in limiting the negative consequences of CMV persistence, demonstrate high prevalence of both TCRα and TCRβ public motif usage, and suggest that a highly diverse TCRαβ repertoire may be an important benchmark and target in the success of immunotherapeutic strategies.

Human West Nile Virus Disease Outbreak in Pakistan, 2015–2016

PubMed Central

Khan, Erum; Barr, Kelli L.; Farooqi, Joveria Qais; Prakoso, Dhani; Abbas, Alizae; Khan, Zain Y.; Ashi, Shanze; Imtiaz, Kehkashan; Aziz, Z.; Malik, Faisal; Lednicky, John A.; Long, Maureen T.

2018-01-01

Like most of the world, Pakistan has seen an increase in mosquito-transmitted diseases in recent years. The magnitude and distribution of these diseases are poorly understood as Pakistan does not have a nation-wide system for reporting disease. A cross-sectional study to determine which flaviviruses were causing of arboviral disease in Pakistan was instituted. West Nile virus (WNV) is a cause of seasonal fever with neurotropic findings in countries that share borders with Pakistan. Here, we describe the active and persistent circulation of WNV in humans in the southern region of Pakistan. This is the first report of WNV causing neurological disease in human patients in this country. Of 997 enrolled patients presenting with clinical features suggestive of arboviral disease, 105 were positive for WNV IgM antibodies, and 71 of these patients possessed WNV-specific neutralizing antibodies. Cross-reactivity of WNV IgM antibodies with Japanese encephalitis virus (JEV) occurred in 75 of these 105 patients. WNV co-infections with Dengue viruses were not a contributing factor for the severity of disease. Nor did prior exposure to dengue virus contribute to incidence of neurological involvement in WNV-infected patients. Patients with WNV infections were more likely to present with altered mental status, seizures, and reduced Glasgow Coma scores when compared with JEV-infected patients. Human WNV cases and vector numbers exhibited a temporal correlation with climate. PMID:29535994

Human West Nile Virus Disease Outbreak in Pakistan, 2015-2016.

PubMed

Khan, Erum; Barr, Kelli L; Farooqi, Joveria Qais; Prakoso, Dhani; Abbas, Alizae; Khan, Zain Y; Ashi, Shanze; Imtiaz, Kehkashan; Aziz, Z; Malik, Faisal; Lednicky, John A; Long, Maureen T

2018-01-01

Like most of the world, Pakistan has seen an increase in mosquito-transmitted diseases in recent years. The magnitude and distribution of these diseases are poorly understood as Pakistan does not have a nation-wide system for reporting disease. A cross-sectional study to determine which flaviviruses were causing of arboviral disease in Pakistan was instituted. West Nile virus (WNV) is a cause of seasonal fever with neurotropic findings in countries that share borders with Pakistan. Here, we describe the active and persistent circulation of WNV in humans in the southern region of Pakistan. This is the first report of WNV causing neurological disease in human patients in this country. Of 997 enrolled patients presenting with clinical features suggestive of arboviral disease, 105 were positive for WNV IgM antibodies, and 71 of these patients possessed WNV-specific neutralizing antibodies. Cross-reactivity of WNV IgM antibodies with Japanese encephalitis virus (JEV) occurred in 75 of these 105 patients. WNV co-infections with Dengue viruses were not a contributing factor for the severity of disease. Nor did prior exposure to dengue virus contribute to incidence of neurological involvement in WNV-infected patients. Patients with WNV infections were more likely to present with altered mental status, seizures, and reduced Glasgow Coma scores when compared with JEV-infected patients. Human WNV cases and vector numbers exhibited a temporal correlation with climate.

Human exposure to Bisphenol A and liver health status: Quantification of urinary and circulating levels by LC-MS/MS.

PubMed

Nicolucci, Carla; Errico, Sonia; Federico, Alessandro; Dallio, Marcello; Loguercio, Carmelina; Diano, Nadia

2017-06-05

A selective and highly sensitive analytical methodology for determination of Bisphenol A in human plasma was developed and validated. The method was based on selective liquid/solid extraction, combined with liquid chromatography-electrospray ionization tandem mass spectrometry in the multiple reaction monitoring mode and negative ionization. The linearity of the detector response was verified in human plasma over the concentration range 0.100-200ngmL -1 . The detection limit was 0.03ngmL -1 and the quantification limit was 0.100ngmL -1 . The analytical features of the proposed in-house validated method were satisfactory: precision was <10% and recoveries were around 84-104%. The matrix effect was studied and compensated using deuterated labeled standard. The applicability of the proposed method was demonstrated analyzing human plasma samples from individuals affected by non-alcoholic fatty liver disease. Bisphenol A was detected above the detection limit in all samples. The data show a persistence of unconjugated Bisphenol A levels in plasma and indicate a chronic Bisphenol A exposure of the target organ, suggesting an association between liver health status and Bisphenol A exposure. The results from our study are valuable for further investigation with large sample size and longitudinal study designs, necessary to confirm the observed association. Copyright © 2017 Elsevier B.V. All rights reserved.

Oxidative injury of the pulmonary circulation in the perinatal period: Short- and long-term consequences for the human cardiopulmonary system

PubMed Central

de Wijs-Meijler, Daphne P.; Duncker, Dirk J.; Tibboel, Dick; Schermuly, Ralph T.; Weissmann, Norbert; Merkus, Daphne; Reiss, Irwin K.M.

2017-01-01

Development of the pulmonary circulation is a complex process with a spatial pattern that is tightly controlled. This process is vulnerable for disruption by various events in the prenatal and early postnatal periods. Disruption of normal pulmonary vascular development leads to abnormal structure and function of the lung vasculature, causing neonatal pulmonary vascular diseases. Premature babies are especially at risk of the development of these diseases, including persistent pulmonary hypertension and bronchopulmonary dysplasia. Reactive oxygen species play a key role in the pathogenesis of neonatal pulmonary vascular diseases and can be caused by hyperoxia, mechanical ventilation, hypoxia, and inflammation. Besides the well-established short-term consequences, exposure of the developing lung to injurious stimuli in the perinatal period, including oxidative stress, may also contribute to the development of pulmonary vascular diseases later in life, through so-called “fetal or perinatal programming.” Because of these long-term consequences, it is important to develop a follow-up program tailored to adolescent survivors of neonatal pulmonary vascular diseases, aimed at early detection of adult pulmonary vascular diseases, and thereby opening the possibility of early intervention and interfering with disease progression. This review focuses on pathophysiologic events in the perinatal period that have been shown to disrupt human normal pulmonary vascular development, leading to neonatal pulmonary vascular diseases that can extend even into adulthood. This knowledge may be particularly important for ex-premature adults who are at risk of the long-term consequences of pulmonary vascular diseases, thereby contributing disproportionately to the burden of adult cardiovascular disease in the future. PMID:28680565

Protein binding and its potential for eliciting minimal systemic side effects with a novel inhaled corticosteroid, ciclesonide.

PubMed

Rohatagi, Shashank; Luo, Yongyi; Shen, Liduo; Guo, Zuyu; Schemm, Christina; Huang, Yongqing; Chen, Kelly; David, Michael; Nave, Ruediger; King, S Peter

2005-01-01

Freely circulating, protein unbound, active inhaled corticosteroid (ICS) can cause systemic adverse effects. Desisobutyryl-ciclesonide (des-CIC) is the active metabolite of ciclesonide, an effective, novel ICS for persistent asthma. This study examines the free fraction of ciclesonide and des-CIC and determines whether the presence of other agents or disease states affects protein binding. Protein binding of des-CIC (0.5, 5.0, 25, 100, and 500 ng/mL) was determined, using both equilibrium dialysis and ultrafiltration, in plasma from humans (healthy and either renally or hepatically impaired) and several animal species and in the presence of either salicylates or warfarin. Dialyzed samples were analyzed by liquid chromatography with tandem mass spectroscopy to determine both free and bound concentrations of des-CIC. After ultrafiltration, spiked plasma plus H-des-CIC was separated into free and bound fractions by centrifugation and quantified by scintillation counting. Additionally, in another study, protein binding of ciclesonide was determined by equilibrium dialysis. For equilibrium dialysis, the mean percentages of des-CIC (0.5-500 ng/mL) plasma protein binding across species were high, approximately 99%, and no apparent saturation of protein binding was observed. Results were similar for ultrafiltration analysis. Protein binding of des-CIC did not change in the presence of warfarin or salicylates or in the plasma of renally or hepatically impaired patients. The protein binding of ciclesonide was 99.4% in human serum. The very low fraction of unbound des-CIC in the systemic circulation suggests minimal systemic exposure of unbound des-CIC, thus suggesting a low potential for systemic adverse effects after administration of inhaled ciclesonide.

A continuum model for pressure-flow relationship in human pulmonary circulation.

PubMed

Huang, Wei; Zhou, Qinlian; Gao, Jian; Yen, R T

2011-06-01

A continuum model was introduced to analyze the pressure-flow relationship for steady flow in human pulmonary circulation. The continuum approach was based on the principles of continuum mechanics in conjunction with detailed measurement of vascular geometry, vascular elasticity and blood rheology. The pulmonary arteries and veins were considered as elastic tubes and the "fifth-power law" was used to describe the pressure-flow relationship. For pulmonary capillaries, the "sheet-flow" theory was employed and the pressure-flow relationship was represented by the "fourth-power law". In this paper, the pressure-flow relationship for the whole pulmonary circulation and the longitudinal pressure distribution along the streamlines were studied. Our computed data showed general agreement with the experimental data for the normal subjects and the patients with mitral stenosis and chronic bronchitis in the literature. In conclusion, our continuum model can be used to predict the changes of steady flow in human pulmonary circulation.

Arctic sea-ice decline weakens the Atlantic Meridional Overturning Circulation

NASA Astrophysics Data System (ADS)

Sévellec, Florian; Fedorov, Alexey V.; Liu, Wei

2017-08-01

The ongoing decline of Arctic sea ice exposes the ocean to anomalous surface heat and freshwater fluxes, resulting in positive buoyancy anomalies that can affect ocean circulation. In this study, we use an optimal flux perturbation framework and comprehensive climate model simulations to estimate the sensitivity of the Atlantic Meridional Overturning Circulation (AMOC) to such buoyancy forcing over the Arctic and globally, and more generally to sea-ice decline. It is found that on decadal timescales, flux anomalies over the subpolar North Atlantic have the largest impact on the AMOC, while on multi-decadal timescales (longer than 20 years), flux anomalies in the Arctic become more important. These positive buoyancy anomalies spread to the North Atlantic, weakening the AMOC and its poleward heat transport. Therefore, the Arctic sea-ice decline may explain the suggested slow-down of the AMOC and the `Warming Hole’ persisting in the subpolar North Atlantic.

Storminess and cold air outbreaks in NE America during AD 1790-1820

NASA Astrophysics Data System (ADS)

van der Schrier, G.; Jones, P. D.

2008-01-01

Two hypotheses have been put forward to explain the anomalously deep trough in winter sea-level pressure in the northwestern Atlantic sector during the AD 1790-1820 period. One relates it to an increase in cyclolysis in this area, the other to a change in the general planetary circulation. In an attempt to distinguish between these hypotheses, storminess and cold air outbreaks (CAO) in the northeastern USA during 1790-1820 are studied, based on a record of daily pressure and temperature observations at Salem (Massachusetts, USA). Frequency changes of CAO act as proxy for planetary circulation changes. It is found that CAO in the early period were both more persistent and severe than those in the modern control period. No evidence of elevated levels of storminess in the 1790-1820 period was found. This suggests that the anomalously deep trough can be attributed mainly to a change in the planetary circulation.

North Atlantic ocean circulation and abrupt climate change during the last glaciation.

PubMed

Henry, L G; McManus, J F; Curry, W B; Roberts, N L; Piotrowski, A M; Keigwin, L D

2016-07-29

The most recent ice age was characterized by rapid and hemispherically asynchronous climate oscillations, whose origin remains unresolved. Variations in oceanic meridional heat transport may contribute to these repeated climate changes, which were most pronounced during marine isotope stage 3, the glacial interval 25 thousand to 60 thousand years ago. We examined climate and ocean circulation proxies throughout this interval at high resolution in a deep North Atlantic sediment core, combining the kinematic tracer protactinium/thorium (Pa/Th) with the deep water-mass tracer, epibenthic δ(13)C. These indicators suggest reduced Atlantic overturning circulation during every cool northern stadial, with the greatest reductions during episodic Hudson Strait iceberg discharges, while sharp northern warming followed reinvigorated overturning. These results provide direct evidence for the ocean's persistent, central role in abrupt glacial climate change. Copyright © 2016, American Association for the Advancement of Science.

Total Cavopulmonary Connection for Functionally Single Ventricle without Cardiopulmonary Bypass Support.

PubMed

Bangash, Sohail Khan; Pathan, Iqbal Hussain; Zaki, Saad Bader

2016-10-01

A heart with two atriums but one ventricle, an anatomy with a unique physiology, is responsible for many creative surgical and interventional approaches in history. Different surgical techniques have been used to address this strange physiology of parallel circulation. All these attempts met with failure till the concept of Fontan circulation was described. Currently, controversy exists between multistage vs. single stage total cavopulmonary connections. Total cavopulmonary connection is the only definitive procedure performed to provide palliation for patients with complex congenital heart defects which cannot support a biventricular circulation. We report a case with tricuspid atresia with transposition of great arteries and pulmonary stenosis with persistant left-sided superior vena cava and functionally single ventricle. Patient successfully underwent single stage extra-cardiac total cavopulmonary connection. In this case, bilateral Glenn with extra-cardiac inferior vena cava to main pulmonary artery shunt was performed off-pump.

The evolution of misoscale circulations in a downburst-producing storm and comparison to numerical results

NASA Technical Reports Server (NTRS)

Kessinger, C. J.; Wilson, J. W.; Weisman, M.; Klemp, J.

1984-01-01

Data from three NCAR radars are used in both single and dual Doppler analyses to trace the evolution of a June 30, 1982 Colorado convective storm containing downburst-type winds and strong vortices 1-2 km in diameter. The analyses show that a series of small circulations formed along a persistent cyclonic shear boundary; at times as many as three misocyclones were present with vertical vorticity values as large as 0.1/s using a 0.25 km grid interval. The strength of the circulations suggests the possibility of accompanying tornadoes or funnels, although none were observed. Dual-Doppler analyses show that strong, small-scale downdrafts develop in close proximity to the misocyclones. A midlevel mesocyclone formed in the same general region of the storm where the misocylones later developed. The observations are compared with numerical simulations from a three-dimensional cloud model initialized with sounding data from the same day.

Environmental surveillance for polioviruses in the Global Polio Eradication Initiative.

PubMed

Asghar, Humayun; Diop, Ousmane M; Weldegebriel, Goitom; Malik, Farzana; Shetty, Sushmitha; El Bassioni, Laila; Akande, Adefunke O; Al Maamoun, Eman; Zaidi, Sohail; Adeniji, Adekunle J; Burns, Cara C; Deshpande, Jagadish; Oberste, M Steve; Lowther, Sara A

2014-11-01

This article summarizes the status of environmental surveillance (ES) used by the Global Polio Eradication Initiative, provides the rationale for ES, gives examples of ES methods and findings, and summarizes how these data are used to achieve poliovirus eradication. ES complements clinical acute flaccid paralysis (AFP) surveillance for possible polio cases. ES detects poliovirus circulation in environmental sewage and is used to monitor transmission in communities. If detected, the genetic sequences of polioviruses isolated from ES are compared with those of isolates from clinical cases to evaluate the relationships among viruses. To evaluate poliovirus transmission, ES programs must be developed in a manner that is sensitive, with sufficiently frequent sampling, appropriate isolation methods, and specifically targeted sampling sites in locations at highest risk for poliovirus transmission. After poliovirus ceased to be detected in human cases, ES documented the absence of endemic WPV transmission and detected imported WPV. ES provides valuable information, particularly in high-density populations where AFP surveillance is of poor quality, persistent virus circulation is suspected, or frequent virus reintroduction is perceived. Given the benefits of ES, GPEI plans to continue and expand ES as part of its strategic plan and as a supplement to AFP surveillance. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

A comparative Study of Circulation Patterns at Active Lava Lakes

NASA Astrophysics Data System (ADS)

Lev, Einat; Oppenheimer, Clive; Spampinato, Letizia; Hernandez, Pedro; Unglert, Kathi

2016-04-01

Lava lakes present a rare opportunity to study magma dynamics in a large scaled-up "crucible" and provide a unique natural laboratory to ground-truth dynamic models of magma circulation. The persistence of lava lakes allows for long-term observations of flow dynamics and of lava properties, especially compared to surface lava flows. There are currently five persistent lava lakes in the world: Halemaumau in Kilauea (Hawaii, USA), Erta Ale (Ethiopia), Nyiragongo (Congo), Erebus (Antarctica), and Villarica (Chile). Marum and Benbow craters of Ambrym volcano (Vanuatu) and Masaya (Nicaragua) have often hosted lava lakes as well. We use visible-light and thermal infrared time-lapse and video footage collected at all above lakes (except Villarica, where the lake is difficult to observe), and compare the circulation patterns recorded. We calculate lake surface motion from the footage using the optical flow method (Lev et al., 2012) to produce 2D velocity fields. We mined both the surface temperature field and the surface velocity field for patterns using machine learning techniques such as "self-organizing maps (SOMs)" and "principle component analysis (PCA)". We use automatic detection technique to study the configuration of crustal plates at the lakes' surface. We find striking differences among the lakes, in flow direction, flow speed, frequency of changes in flow direction and speed, location and consistency of upwelling and downwelling, and crustal plate configuration. We relate the differences to lake size, shallow conduit geometry, lava viscosity, crystal and gas content, and crust integrity.

Leucine acts in the brain to suppress food intake but does not function as a physiological signal of low dietary protein

PubMed Central

Laeger, Thomas; Reed, Scott D.; Henagan, Tara M.; Fernandez, Denise H.; Taghavi, Marzieh; Addington, Adele; Münzberg, Heike; Martin, Roy J.; Hutson, Susan M.

2014-01-01

Intracerebroventricular injections of leucine are sufficient to suppress food intake, but it remains unclear whether brain leucine signaling represents a physiological signal of protein balance. We tested whether variations in dietary and circulating levels of leucine, or all three branched-chain amino acids (BCAAs), contribute to the detection of reduced dietary protein. Of the essential amino acids (EAAs) tested, only intracerebroventricular injection of leucine (10 μg) was sufficient to suppress food intake. Isocaloric low- (9% protein energy; LP) or normal- (18% protein energy) protein diets induced a divergence in food intake, with an increased consumption of LP beginning on day 2 and persisting throughout the study (P < 0.05). Circulating BCAA levels were reduced the day after LP diet exposure, but levels subsequently increased and normalized by day 4, despite persistent hyperphagia. Brain BCAA levels as measured by microdialysis on day 2 of diet exposure were reduced in LP rats, but this effect was most prominent postprandially. Despite these diet-induced changes in BCAA levels, reducing dietary leucine or total BCAAs independently from total protein was neither necessary nor sufficient to induce hyperphagia, while chronic infusion of EAAs into the brain of LP rats failed to consistently block LP-induced hyperphagia. Collectively, these data suggest that circulating BCAAs are transiently reduced by dietary protein restriction, but variations in dietary or brain BCAAs alone do not explain the hyperphagia induced by a low-protein diet. PMID:24898843

In Vivo Persistence of Human Rhinoviruses in Immunosuppressed Patients

PubMed Central

Engelmann, Ilka; Dewilde, Anny; Lazrek, Mouna; Batteux, Mathilde; Hamissi, Aminati; Yakoub-Agha, Ibrahim; Hober, Didier

2017-01-01

Several species of the genus Enterovirus cause persistent infections in humans. Human rhinovirus (HRV) infections are generally self-limiting but occasionally persistent infections have been described. This study aimed to identify persistent HRV infections and investigate the clinical and virologic characteristics of patients with persistent infections. From January 2012 to March 2015, 3714 respiratory specimens from 2608 patients were tested for respiratory viruses by using a multiplex reverse transcription–polymerase chain reaction. A retrospective study was performed. Patients with at least two specimens positive for HRV/enterovirus taken 45 days or longer apart were identified and the HRV/enteroviruses were typed. Patients with persistent infection were compared to patients with reinfection and patients with cleared infection. Phylogenetic analysis of the viral protein(VP)4/VP2 region was performed. 18 patients with persistent HRV/enterovirus infection were identified. Minimum median duration of persistence was 92 days (range 50–455 days). All but one patients with persistence were immunosuppressed. Immunosuppression and hematologic disorders were more frequent in patients with persistence (n = 18) than in patients with reinfection (n = 33) and with cleared infection (n = 25) (p = 0.003 and p = 0.001, respectively). In conclusion, this retrospective study identified HRV persistence in vivo which occurred mainly in immunosuppressed patients. PMID:28151988

Sustainability of keratinocyte gene transfer and cell survival in vivo.

PubMed

Choate, K A; Khavari, P A

1997-05-20

The epidermis is an attractive site for therapeutic gene delivery because it is accessible and capable of delivering polypeptides to the systemic circulation. A number of difficulties, however, have emerged in attempts at cutaneous gene delivery, and central among these is an inability to sustain therapeutic gene production. We have examined two major potential contributing factors, viral vector stamina and involvement of long-lived epidermal progenitor cells. Human keratinocytes were either untreated or transduced with a retroviral vector for beta-galactosidase (beta-Gal) at > 99% efficiency and then grafted onto immunodeficient mice to regenerate human epidermis. Human epidermis was monitored in vivo after grafting for clinical and histologic appearance as well as for gene expression. Although integrated vector sequences persisted unchanged in engineered epidermis at 10 weeks post-grafting, retroviral long terminal repeat (LTR)-driven beta-Gal expression ceased in vivo after approximately 4 weeks. Endogenous cellular promoters, however, maintained consistently normal gene expression levels without evidence of time-dependent decline, as determined by immunostaining with species-specific antibodies for human involucrin, filaggrin, keratinocyte transglutaminase, keratin 10, type VII collagen, and Laminin 5 proteins out to week 14 post-grafting. Transduced human keratinocytes generated multilayer epidermis sustained through multiple epidermal turnover cycles; this epidermis demonstrated retention of a spatially appropriate pattern of basal and suprabasal epidermal marker gene expression. These results confirm previous findings suggesting that viral promoter-driven gene expression is not durable and demonstrate that keratinocytes passaged in vitro can regenerate and sustain normal epidermis for prolonged periods.

Effects of captopril on the human foetal placental circulation: an interaction with bradykinin and angiotensin I.

PubMed Central

de Moura, R; Lopes, M A

1995-01-01

1. The mechanism underlying the foetal toxicity induced by captopril is not well understood. Since bradykinin and angiotensin II appear to be important in the regulation of the placental circulation, experiments were performed to assess the effects of captopril on the vascular actions of these peptides on the human foetal placental circulation. 2. Full-term human placentas, obtained from normal pregnancy, were perfused with a modified Tyrode solution bubbled with O2 using a pulsatile pump. The placental perfusion pressure was measured with a Statham pressure transducer and recorded continuously on a Hewlett-Packard polygraph. 3. Bradykinin (0.1, 0.3 and 1.0 nmol) injected into the placental arterial circulation produced an increase in placental perfusion pressure in all experiments. This effect of bradykinin was significantly inhibited by indomethacin (3 x 10(-7) M). 4. Captopril (10(-7) M) significantly potentiated the pressor effect of bradykinin on the human placental circulation (n = 6). This effect of captopril was reversed by indomethacin (3 x 10(-7) M). 5. Angiotensin I (n = 6) and angiotensin II (n = 6), injected into the placental arterial circulation, both produced dose-dependent increases in placental perfusion pressure. The dose-response curves to angiotensin I (n = 6) were significantly displaced to the right by captopril in a concentration-dependent manner. 6. We suggest that the toxic effects of captopril on the foetus, rather than reflecting an inhibition of angiotensin II formation, may instead be related to a potentiation of the vasoconstrictor effect of bradykinin on the foetal placental circulation, thereby reducing blood flow and causing foetal damage. The reasons for this are discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7669485

The role of viral persistence in flavivirus biology

PubMed Central

Mlera, Luwanika; Melik, Wessam; Bloom, Marshall E.

2014-01-01

In nature, vector-borne flaviviruses are persistently cycled between either the tick or mosquito vector and small mammals such as rodents, skunks, and swine. These viruses account for considerable human morbidity and mortality worldwide. Increasing and substantial evidence of viral persistence in humans, which includes the isolation of RNA by RT-PCR and infectious virus by culture, continues to be reported. Viral persistence can also be established in vitro in various human, animal, arachnid and insect cell lines in culture. Although some research has focused on the potential roles of defective virus particles, evasion of the immune response through the manipulation of autophagy and/or apoptosis, the precise mechanism of flavivirus persistence is still not well understood. We propose additional research for further understanding of how viral persistence is established in different systems. Avenues for additional studies include determining if the multifunctional flavivirus protein NS5 has a role in viral persistence, the development of relevant animal models of viral persistence as well as investigating the host responses that allow vector borne flavivirus replication without detrimental effects on infected cells. Such studies might shed more light on the viral-host relationships, and could be used to unravel the mechanisms for establishment of persistence. PMID:24737600

21 CFR 868.5250 - Breathing circuit circulator.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Breathing circuit circulator. 868.5250 Section 868.5250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5250 Breathing circuit circulator. (a...

21 CFR 868.5250 - Breathing circuit circulator.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Breathing circuit circulator. 868.5250 Section 868.5250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5250 Breathing circuit circulator. (a...

Metacommunity and phylogenetic structure determine wildlife and zoonotic infectious disease patterns in time and space.

PubMed

Suzán, Gerardo; García-Peña, Gabriel E; Castro-Arellano, Ivan; Rico, Oscar; Rubio, André V; Tolsá, María J; Roche, Benjamin; Hosseini, Parviez R; Rizzoli, Annapaola; Murray, Kris A; Zambrana-Torrelio, Carlos; Vittecoq, Marion; Bailly, Xavier; Aguirre, A Alonso; Daszak, Peter; Prieur-Richard, Anne-Helene; Mills, James N; Guégan, Jean-Francois

2015-02-01

The potential for disease transmission at the interface of wildlife, domestic animals and humans has become a major concern for public health and conservation biology. Research in this subject is commonly conducted at local scales while the regional context is neglected. We argue that prevalence of infection at local and regional levels is influenced by three mechanisms occurring at the landscape level in a metacommunity context. First, (1) dispersal, colonization, and extinction of pathogens, reservoir or vector hosts, and nonreservoir hosts, may be due to stochastic and niche-based processes, thus determining distribution of all species, and then their potential interactions, across local communities (metacommunity structure). Second, (2) anthropogenic processes may drive environmental filtering of hosts, nonhosts, and pathogens. Finally, (3) phylogenetic diversity relative to reservoir or vector host(s), within and between local communities may facilitate pathogen persistence and circulation. Using a metacommunity approach, public heath scientists may better evaluate the factors that predispose certain times and places for the origin and emergence of infectious diseases. The multidisciplinary approach we describe fits within a comprehensive One Health and Ecohealth framework addressing zoonotic infectious disease outbreaks and their relationship to their hosts, other animals, humans, and the environment.

Tomato Infection by Whitefly-Transmitted Circulative and Non-Circulative Viruses Induce Contrasting Changes in Plant Volatiles and Vector Behaviour

PubMed Central

Fereres, Alberto; Peñaflor, Maria Fernanda G. V.; Favaro, Carla F.; Azevedo, Kamila E. X.; Landi, Carolina H.; Maluta, Nathalie K. P.; Bento, José Mauricio S.; Lopes, Joao R.S.

2016-01-01

Virus infection frequently modifies plant phenotypes, leading to changes in behaviour and performance of their insect vectors in a way that transmission is enhanced, although this may not always be the case. Here, we investigated Bemisia tabaci response to tomato plants infected by Tomato chlorosis virus (ToCV), a non-circulative-transmitted crinivirus, and Tomato severe rugose virus (ToSRV), a circulative-transmitted begomovirus. Moreover, we examined the role of visual and olfactory cues in host plant selection by both viruliferous and non-viruliferous B. tabaci. Visual cues alone were assessed as targets for whitefly landing by placing leaves underneath a Plexiglas plate. A dual-choice arena was used to assess whitefly response to virus-infected and mock-inoculated tomato leaves under light and dark conditions. Thereafter, we tested the whitefly response to volatiles using an active air-flow Y-tube olfactometer, and chemically characterized the blends using gas chromatography coupled to mass spectrometry. Visual stimuli tests showed that whiteflies, irrespective of their infectious status, always preferred to land on virus-infected rather than on mock-inoculated leaves. Furthermore, whiteflies had no preference for either virus-infected or mock-inoculated leaves under dark conditions, but preferred virus-infected leaves in the presence of light. ToSRV-infection promoted a sharp decline in the concentration of some tomato volatiles, while an increase in the emission of some terpenes after ToCV infection was found. ToSRV-viruliferous whiteflies preferred volatiles emitted from mock-inoculated plants, a conducive behaviour to enhance virus spread, while volatiles from ToCV-infected plants were avoided by non-viruliferous whiteflies, a behaviour that is likely detrimental to the secondary spread of the virus. In conclusion, the circulative persistent begomovirus, ToSRV, seems to have evolved together with its vector B. tabaci to optimise its own spread. However, this type of virus-induced manipulation of vector behaviour was not observed for the semi persistent crinivirus, ToCV, which is not specifically transmitted by B. tabaci and has a much less intimate virus-vector relationship. PMID:27529271

Tomato Infection by Whitefly-Transmitted Circulative and Non-Circulative Viruses Induce Contrasting Changes in Plant Volatiles and Vector Behaviour.

PubMed

Fereres, Alberto; Peñaflor, Maria Fernanda G V; Favaro, Carla F; Azevedo, Kamila E X; Landi, Carolina H; Maluta, Nathalie K P; Bento, José Mauricio S; Lopes, Joao R S

2016-08-11

Virus infection frequently modifies plant phenotypes, leading to changes in behaviour and performance of their insect vectors in a way that transmission is enhanced, although this may not always be the case. Here, we investigated Bemisia tabaci response to tomato plants infected by Tomato chlorosis virus (ToCV), a non-circulative-transmitted crinivirus, and Tomato severe rugose virus (ToSRV), a circulative-transmitted begomovirus. Moreover, we examined the role of visual and olfactory cues in host plant selection by both viruliferous and non-viruliferous B. tabaci. Visual cues alone were assessed as targets for whitefly landing by placing leaves underneath a Plexiglas plate. A dual-choice arena was used to assess whitefly response to virus-infected and mock-inoculated tomato leaves under light and dark conditions. Thereafter, we tested the whitefly response to volatiles using an active air-flow Y-tube olfactometer, and chemically characterized the blends using gas chromatography coupled to mass spectrometry. Visual stimuli tests showed that whiteflies, irrespective of their infectious status, always preferred to land on virus-infected rather than on mock-inoculated leaves. Furthermore, whiteflies had no preference for either virus-infected or mock-inoculated leaves under dark conditions, but preferred virus-infected leaves in the presence of light. ToSRV-infection promoted a sharp decline in the concentration of some tomato volatiles, while an increase in the emission of some terpenes after ToCV infection was found. ToSRV-viruliferous whiteflies preferred volatiles emitted from mock-inoculated plants, a conducive behaviour to enhance virus spread, while volatiles from ToCV-infected plants were avoided by non-viruliferous whiteflies, a behaviour that is likely detrimental to the secondary spread of the virus. In conclusion, the circulative persistent begomovirus, ToSRV, seems to have evolved together with its vector B. tabaci to optimise its own spread. However, this type of virus-induced manipulation of vector behaviour was not observed for the semi persistent crinivirus, ToCV, which is not specifically transmitted by B. tabaci and has a much less intimate virus-vector relationship.

A review of the Southern Oscillation - Oceanic-atmospheric circulation changes and related rainfall anomalies

NASA Technical Reports Server (NTRS)

Kousky, V. E.; Kagano, M. T.; Cavalcanti, I. F. A.

1984-01-01

The region of South America is emphasized in the present consideration of the Southern Oscillation (SO) oceanic and atmospheric circulation changes. The persistence of climate anomalies associated with El Nino-SO events is due to strong atmosphere-ocean coupling. Once initiated, the SO follows a certain sequence of events with clearly defined effects on tropical and subtropical rainfall. Excessive rainfall related to the SO in the central and eastern Pacific, Peru, Ecuador, and southern Brazil, are complemented by drought in Australia, Indonesia, India, West Africa, and northeast Brazil. El Nino-SO events are also associated with dramatic changes in the tropospheric flow pattern over a broad area of both hemispheres.

Climate Change in the North American Arctic: A One Health Perspective.

PubMed

Dudley, Joseph P; Hoberg, Eric P; Jenkins, Emily J; Parkinson, Alan J

2015-12-01

Climate change is expected to increase the prevalence of acute and chronic diseases among human and animal populations within the Arctic and subarctic latitudes of North America. Warmer temperatures are expected to increase disease risks from food-borne pathogens, water-borne diseases, and vector-borne zoonoses in human and animal populations of Arctic landscapes. Existing high levels of mercury and persistent organic pollutant chemicals circulating within terrestrial and aquatic ecosystems in Arctic latitudes are a major concern for the reproductive health of humans and other mammals, and climate warming will accelerate the mobilization and biological amplification of toxic environmental contaminants. The adverse health impacts of Arctic warming will be especially important for wildlife populations and indigenous peoples dependent upon subsistence food resources from wild plants and animals. Additional research is needed to identify and monitor changes in the prevalence of zoonotic pathogens in humans, domestic dogs, and wildlife species of critical subsistence, cultural, and economic importance to Arctic peoples. The long-term effects of climate warming in the Arctic cannot be adequately predicted or mitigated without a comprehensive understanding of the interactive and synergistic effects between environmental contaminants and pathogens in the health of wildlife and human communities in Arctic ecosystems. The complexity and magnitude of the documented impacts of climate change on Arctic ecosystems, and the intimacy of connections between their human and wildlife communities, makes this region an appropriate area for development of One Health approaches to identify and mitigate the effects of climate warming at the community, ecosystem, and landscape scales.

Metabolic fate of strawberry polyphenols after chronic intake in healthy older adults.

PubMed

Sandhu, Amandeep K; Miller, Marshall G; Thangthaeng, Nopporn; Scott, Tammy M; Shukitt-Hale, Barbara; Edirisinghe, Indika; Burton-Freeman, Britt

2018-01-24

Strawberries contain a wide array of nutrients and phytochemicals including polyphenols such as anthocyanins, proanthocyanidins and ellagitannins. These polyphenols are absorbed and metabolized to various phenolic metabolites/conjugates in the body, which may play a role in disease risk reduction. In the present study, we investigated the metabolic fate of strawberry polyphenols after chronic (90 days) supplementation of freeze-dried strawberry (24 g d -1 , equivalent to 2 cups of fresh strawberries) vs. control powder in 19 healthy older adults. Blood samples were collected at two time-points i.e., fasting (t = 0 h) and 2 h after the breakfast meal. On days 45 and 90 breakfast also included a control or strawberry drink consistent with their treatment randomization. A total of 21 polyphenolic metabolites were quantified in plasma consisting of 3 anthocyanins/metabolites, 3 urolithin metabolites and 15 phenolic acid metabolites. Among anthocyanins/metabolite, pelargonidin glucuronide (85.7 ± 9.0 nmol L -1 , t = 2 h, day 90) was present in the highest concentration. Persistent concentrations of anthocyanins/metabolites, urolithins and some phenolic acids were observed in fasting (t = 0 h) plasma samples on day 45 and 90 after strawberry drink consumption suggesting a role of enteric, enterohepatic recycling or upregulation of gut microbial and/or human metabolism of these compounds. Our results suggest that strawberry polyphenols are absorbed and extensively metabolized, and can persist in the circulation.

Advanced glycation in health and disease: role of the modern environment.

PubMed

Vlassara, Helen

2005-06-01

It is believed that intracellular and extracellular advanced glycation (AGEs) or lipoxidation end products (ALEs), together with dysregulated glucose and lipid metabolism, are important contributors to oxidant or carbonyl stress, enhanced cellular redox-sensitive transcription factor activity, and impaired innate immune defense, causing over time inappropriate inflammatory responses. However, neither the magnitude nor the persistent nature of this increased prooxidant state are completely understood. A significant correlation has been found between ingested and circulating AGEs in humans in recent years. Based on animal studies, the injurious impact of diet-derived AGEs to vascular and kidney tissues is estimated to rival or even exceed that caused by hyperglycemia or hyperlipidemia. Consistent with this view, dietary AGE restriction has been associated with suppression of several immune defects, insulin resistance, and diabetic complications, whether genetically or diet induced, despite persistent diabetes. These findings are in support of clinical evidence from subjects with diabetes or vascular or kidney disease. Most recently, evidence from animal studies points to AGE restriction as an effective means for extending median life span, similar to that previously shown by marked caloric restriction. We conclude that excessive AGE consumption, in the current dietary/social structure, represents an independent factor for inappropriate oxidant stress responses, which may promote the premature expression of complex diseases associated with adult life, such as diabetes and cardiovascular disease.

Rethinking International Migration of Human Capital and Brain Circulation: The Case of Chinese-Canadian Academics

ERIC Educational Resources Information Center

Blachford, Dongyan Ru; Zhang, Bailing

2014-01-01

This article examines the dynamics of brain circulation through a historical review of the debates over international migration of human capital and a case study on Chinese-Canadian academics. Interviews with 22 Chinese-Canadian professors who originally came from China provide rich data regarding the possibilities and problems of the contemporary…

Does Every Cell Get Blood? Young Students' Discussions about Illustrations of Human Blood Circulation

ERIC Educational Resources Information Center

Westman, Anna-Karin; Karlsson, Karl-Goran

2016-01-01

This article presents a study of how groups of young students discuss illustrations of human blood circulation. Transparency is not an innate quality of illustrations, visual information is always coded and interpretations are always related to culture and context. Results of this study are discussed with reference to Kress and van Leeuwens'…

Sex differences and the impact of steroid hormones on the developing human brain.

PubMed

Neufang, Susanne; Specht, Karsten; Hausmann, Markus; Güntürkün, Onur; Herpertz-Dahlmann, Beate; Fink, Gereon R; Konrad, Kerstin

2009-02-01

Little is known about the hormonal effects of puberty on the anatomy of the developing human brain. In a voxel-based morphometry study, sex-related differences in gray matter (GM) volume were examined in 46 subjects aged 8-15 years. Males had larger GM volumes in the left amygdala, whereas females had larger right striatal and bilateral hippocampal GM volumes than males. Sexually dimorphic areas were related to Tanner stages (TS) of pubertal development and to circulating level of steroid hormones in a subsample of 30 subjects. Regardless of sex, amygdala and hippocampal volumes varied as a function of TS and were associated with circulating testosterone (TEST) levels. By contrast, striatal GM volumes were unrelated to pubertal development and circulating steroid hormones. Whole-brain regression analyses revealed positive associations between circulating estrogen levels and parahippocampal GM volumes as well as between TEST levels and diencephalic brain structures. In addition, a negative association was found between circulating TEST and left parietal GM volumes. These data suggest that GM development in certain brain regions is associated with sexual maturation and that pubertal hormones might have organizational effects on the developing human brain.

Potential predictability and forecast skill in ensemble climate forecast: a skill-persistence rule

NASA Astrophysics Data System (ADS)

Jin, Yishuai; Rong, Xinyao; Liu, Zhengyu

2017-12-01

This study investigates the factors relationship between the forecast skills for the real world (actual skill) and perfect model (perfect skill) in ensemble climate model forecast with a series of fully coupled general circulation model forecast experiments. It is found that the actual skill for sea surface temperature (SST) in seasonal forecast is substantially higher than the perfect skill on a large part of the tropical oceans, especially the tropical Indian Ocean and the central-eastern Pacific Ocean. The higher actual skill is found to be related to the higher observational SST persistence, suggesting a skill-persistence rule: a higher SST persistence in the real world than in the model could overwhelm the model bias to produce a higher forecast skill for the real world than for the perfect model. The relation between forecast skill and persistence is further proved using a first-order autoregressive model (AR1) analytically for theoretical solutions and numerically for analogue experiments. The AR1 model study shows that the skill-persistence rule is strictly valid in the case of infinite ensemble size, but could be distorted by sampling errors and non-AR1 processes. This study suggests that the so called "perfect skill" is model dependent and cannot serve as an accurate estimate of the true upper limit of real world prediction skill, unless the model can capture at least the persistence property of the observation.

Chinese Returnees from Overseas Study: An Understanding of Brain Gain and Brain Circulation in the Age of Globalization

ERIC Educational Resources Information Center

Ma, Yuping; Pan, Suyan

2015-01-01

Among discussions on international academic mobility, a persistent challenge is to understand whether education abroad can become a source of brain gain, and whether globalization can offer source countries the hope that they might enjoy the benefits of freer crossborder flows in information and personnel. With reference to China, this article…

Association of mixed hematopoietic chimerism with elevated circulating autoantibodies and chronic graft-versus-host disease occurrence.

PubMed

Perruche, Sylvain; Marandin, Aliette; Kleinclauss, François; Angonin, Régis; Fresnay, Stéphanie; Baron, Marie Hélène; Tiberghien, Pierre; Saas, Philippe

2006-02-27

Use of a reduced-intensity conditioning regimen before an allogeneic hematopoietic cell transplantation is frequently associated with an early state of mixed hematopoietic chimerism. Such a coexistence of both host and donor hematopoietic cells may influence posttransplant alloreactivity and may affect the occurrence and severity of acute and chronic graft-versus-host disease (GVHD) as well as the intensity of the graft-versus-leukemia effect. Here we evaluated the relation between chimerism state after reduced-intensity conditioning transplantation (RICT), autoantibody production, and chronic GVHD (cGVHD)-related pathology. Chimerism state, circulating anticardiolipin, and antidouble stranded DNA autoantibody (Ab) titers as well as occurrence of cGVHD-like lesions were investigated in a murine RICT model. We observed a novel association between mixed chimerism state, high levels of pathogenic IgG autoantibodies, and subsequent development of cGVHD-like lesions. Furthermore, we found that the persistence of host B cells, but not dendritic cell origin or subset, was a factor associated with the appearance of cGVHD-like lesions. The implication of host B cells was confirmed by a host origin of autoantibodies. Recipient B cell persistence may contribute to the frequency and/or severity of cGVHD after RICT.

A persistent northern boundary of Indian Summer Monsoon precipitation over Central Asia during the Holocene.

PubMed

Ramisch, Arne; Lockot, Gregori; Haberzettl, Torsten; Hartmann, Kai; Kuhn, Gerhard; Lehmkuhl, Frank; Schimpf, Stefan; Schulte, Philipp; Stauch, Georg; Wang, Rong; Wünnemann, Bernd; Yan, Dada; Zhang, Yongzhan; Diekmann, Bernhard

2016-05-13

Extra-tropical circulation systems impede poleward moisture advection by the Indian Summer Monsoon. In this context, the Himalayan range is believed to insulate the south Asian circulation from extra-tropical influences and to delineate the northern extent of the Indian Summer Monsoon in central Asia. Paleoclimatic evidence, however, suggests increased moisture availability in the Early Holocene north of the Himalayan range which is attributed to an intensification of the Indian Summer Monsoon. Nevertheless, mechanisms leading to a surpassing of the Himalayan range and the northern maximum extent of summer monsoonal influence remain unknown. Here we show that the Kunlun barrier on the northern Tibetan Plateau [~36°N] delimits Indian Summer Monsoon precipitation during the Holocene. The presence of the barrier relocates the insulation effect 1,000 km further north, allowing a continental low intensity branch of the Indian Summer Monsoon which is persistent throughout the Holocene. Precipitation intensities at its northern extent seem to be driven by differentiated solar heating of the Northern Hemisphere indicating dependency on energy-gradients rather than absolute radiation intensities. The identified spatial constraints of monsoonal precipitation will facilitate the prediction of future monsoonal precipitation patterns in Central Asia under varying climatic conditions.

Avian Influenza Virus Infection of Immortalized Human Respiratory Epithelial Cells Depends upon a Delicate Balance between Hemagglutinin Acid Stability and Endosomal pH*

PubMed Central

Daidoji, Tomo; Watanabe, Yohei; Ibrahim, Madiha S.; Yasugi, Mayo; Maruyama, Hisataka; Masuda, Taisuke; Arai, Fumihito; Ohba, Tomoyuki; Honda, Ayae; Ikuta, Kazuyoshi; Nakaya, Takaaki

2015-01-01

The highly pathogenic avian influenza (AI) virus, H5N1, is a serious threat to public health worldwide. Both the currently circulating H5N1 and previously circulating AI viruses recognize avian-type receptors; however, only the H5N1 is highly infectious and virulent in humans. The mechanism(s) underlying this difference in infectivity remains unclear. The aim of this study was to clarify the mechanisms responsible for the difference in infectivity between the current and previously circulating strains. Primary human small airway epithelial cells (SAECs) were transformed with the SV40 large T-antigen to establish a series of clones (SAEC-Ts). These clones were then used to test the infectivity of AI strains. Human SAEC-Ts could be broadly categorized into two different types based on their susceptibility (high or low) to the viruses. SAEC-T clones were poorly susceptible to previously circulating AI but were completely susceptible to the currently circulating H5N1. The hemagglutinin (HA) of the current H5N1 virus showed greater membrane fusion activity at higher pH levels than that of previous AI viruses, resulting in broader cell tropism. Moreover, the endosomal pH was lower in high susceptibility SAEC-T clones than that in low susceptibility SAEC-T clones. Taken together, the results of this study suggest that the infectivity of AI viruses, including H5N1, depends upon a delicate balance between the acid sensitivity of the viral HA and the pH within the endosomes of the target cell. Thus, one of the mechanisms underlying H5N1 pathogenesis in humans relies on its ability to fuse efficiently with the endosomes in human airway epithelial cells. PMID:25673693

Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium.

PubMed

Humby, Frances; Bombardieri, Michele; Manzo, Antonio; Kelly, Stephen; Blades, Mark C; Kirkham, Bruce; Spencer, Jo; Pitzalis, Costantino

2009-01-13

Follicular structures resembling germinal centres (GCs) that are characterized by follicular dendritic cell (FDC) networks have long been recognized in chronically inflamed tissues in autoimmune diseases, including the synovium of rheumatoid arthritis (RA). However, it is debated whether these ectopic structures promote autoimmunity and chronic inflammation driving the production of pathogenic autoantibodies. Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific markers of RA, predict a poor prognosis, and have been suggested to be pathogenic. Therefore, the main study objectives were to determine whether ectopic lymphoid structures in RA synovium: (i) express activation-induced cytidine deaminase (AID), the enzyme required for somatic hypermutation and class-switch recombination (CSR) of Ig genes; (ii) support ongoing CSR and ACPA production; and (iii) remain functional in a RA/severe combined immunodeficiency (SCID) chimera model devoid of new immune cell influx into the synovium. Using immunohistochemistry (IHC) and quantitative Taqman real-time PCR (QT-PCR) in synovial tissue from 55 patients with RA, we demonstrated that FDC+ structures invariably expressed AID with a distribution resembling secondary lymphoid organs. Further, AID+/CD21+ follicular structures were surrounded by ACPA+/CD138+ plasma cells, as demonstrated by immune reactivity to citrullinated fibrinogen. Moreover, we identified a novel subset of synovial AID+/CD20+ B cells outside GCs resembling interfollicular large B cells. In order to gain direct functional evidence that AID+ structures support CSR and in situ manufacturing of class-switched ACPA, 34 SCID mice were transplanted with RA synovium and humanely killed at 4 wk for harvesting of transplants and sera. Persistent expression of AID and Igamma-Cmu circular transcripts (identifying ongoing IgM-IgG class-switching) was observed in synovial grafts expressing FDCs/CD21L. Furthermore, synovial mRNA levels of AID were closely associated with circulating human IgG ACPA in mouse sera. Finally, the survival and proliferation of functional B cell niches was associated with persistent overexpression of genes regulating ectopic lymphoneogenesis. Our demonstration that FDC+ follicular units invariably express AID and are surrounded by ACPA-producing plasma cells provides strong evidence that ectopic lymphoid structures in the RA synovium are functional and support autoantibody production. This concept is further confirmed by evidence of sustained AID expression, B cell proliferation, ongoing CSR, and production of human IgG ACPA from GC+ synovial tissue transplanted into SCID mice, independently of new B cell influx from the systemic circulation. These data identify AID as a potential therapeutic target in RA and suggest that survival of functional synovial B cell niches may profoundly influence chronic inflammation, autoimmunity, and response to B cell-depleting therapies.

Transmissibility and persistence of oral polio vaccine viruses: implications for the global poliomyelitis eradication initiative.

PubMed

Fine, P E; Carneiro, I A

1999-11-15

The global poliomyelitis eradication initiative has been a tremendous success, with current evidence suggesting that wild poliovirus will cease to circulate anywhere in the world soon after the year 2000. As the goal of wild poliovirus eradication is approached, concern has been raised about the potential for persistent transmission of oral polio vaccine (OPV) viruses, as these viruses are known to revert toward wild-type neurovirulence. This paper has been extracted from a document prepared for the World Health Organization on the implications of OPV transmissibility for the strategy of stopping OPV vaccination after global eradication of wild polioviruses. The authors review the empirical evidence on OPV transmissibility available from household and community transmission studies and from mass-vaccination experiences. They then consider theoretical measures of transmissibility and persistence for wild and OPV viruses (secondary attack rate, basic reproduction number, and critical populations' size), to assess whether transmissibility of OPV viruses is sufficient to allow persistence of these viruses after cessation of vaccination. The findings indicate that OPV viruses could persist under various plausible circumstances, and that this potential should be a major consideration when planning the cessation of OPV vaccination.

The human circulating miRNome reflects multiple organ disease risks in association with short-term exposure to traffic-related air pollution.

PubMed

Krauskopf, Julian; Caiment, Florian; van Veldhoven, Karin; Chadeau-Hyam, Marc; Sinharay, Rudy; Chung, Kian Fan; Cullinan, Paul; Collins, Peter; Barratt, Benjamin; Kelly, Frank J; Vermeulen, Roel; Vineis, Paolo; de Kok, Theo M; Kleinjans, Jos C

2018-04-01

Traffic-related air pollution is a complex mixture of particulate matter (PM) and gaseous pollutants, such as nitrogen dioxide (NO2). PM exposure contributes to the pathogenesis of many diseases including several types of cancer, as well as pulmonary, cardiovascular and neurodegenerative diseases. Also exposure to NO2 has been related to increased cardiovascular mortality. In search of an early diagnostic biomarker for improved air pollution-associated health risk assessment, recent human studies have shown that certain circulating miRNAs are altered upon exposure to traffic-related air pollutants. Here, we present for the first time a global analysis of the circulating miRNA genome in an experimental cross-over study of a human population exposed to traffic-related air pollution. By utilizing next-generation sequencing technology and detailed real-time exposure measurements we identified 54 circulating miRNAs to be dose- and pollutant species-dependently associated with PM10, PM2.5, black carbon, ultrafine particles and NO2 already after 2 h of exposure. Bioinformatics analysis suggests that these circulating miRNAs actually reflect the adverse consequences of traffic pollution-induced toxicity in target tissues including the lung, heart, kidney and brain. This study shows the strong potential of circulating miRNAs as novel biomarkers for environmental health risk assessment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ocean impact on decadal Atlantic climate variability revealed by sea-level observations.

PubMed

McCarthy, Gerard D; Haigh, Ivan D; Hirschi, Joël J-M; Grist, Jeremy P; Smeed, David A

2015-05-28

Decadal variability is a notable feature of the Atlantic Ocean and the climate of the regions it influences. Prominently, this is manifested in the Atlantic Multidecadal Oscillation (AMO) in sea surface temperatures. Positive (negative) phases of the AMO coincide with warmer (colder) North Atlantic sea surface temperatures. The AMO is linked with decadal climate fluctuations, such as Indian and Sahel rainfall, European summer precipitation, Atlantic hurricanes and variations in global temperatures. It is widely believed that ocean circulation drives the phase changes of the AMO by controlling ocean heat content. However, there are no direct observations of ocean circulation of sufficient length to support this, leading to questions about whether the AMO is controlled from another source. Here we provide observational evidence of the widely hypothesized link between ocean circulation and the AMO. We take a new approach, using sea level along the east coast of the United States to estimate ocean circulation on decadal timescales. We show that ocean circulation responds to the first mode of Atlantic atmospheric forcing, the North Atlantic Oscillation, through circulation changes between the subtropical and subpolar gyres--the intergyre region. These circulation changes affect the decadal evolution of North Atlantic heat content and, consequently, the phases of the AMO. The Atlantic overturning circulation is declining and the AMO is moving to a negative phase. This may offer a brief respite from the persistent rise of global temperatures, but in the coupled system we describe, there are compensating effects. In this case, the negative AMO is associated with a continued acceleration of sea-level rise along the northeast coast of the United States.

Temperature-dependent persistence of human norovirus within oysters (Crassotrea virginica)

USDA-ARS?s Scientific Manuscript database

This study characterizes the persistence of human norovirus in Eastern oysters (Crassostrea virginica) held at different seawater temperatures. Oysters were contaminated with human norovirus GI.1 (Norwalk strain 8fIIa) by exposing them to virus contaminated water at 15 degrees C, and subsequently ho...

Usutu virus persistence and West Nile virus inactivity in the Emilia-Romagna region (Italy) in 2011.

PubMed

Calzolari, Mattia; Bonilauri, Paolo; Bellini, Romeo; Albieri, Alessandro; Defilippo, Francesco; Tamba, Marco; Tassinari, Massimo; Gelati, Antonio; Cordioli, Paolo; Angelini, Paola; Dottori, Michele

2013-01-01

The circulation of West Nile virus and Usutu virus was detected in the Emilia-Romagna region in 2008 and 2009. To evaluate the extent of circulation of both viruses, environmental surveillance, based on bird and mosquito testing, was conducted in 2008 and gradually improved over the years. In February-March 2009-2011, 5,993 hibernating mosquitoes were manually sampled, out of which 80.1% were Culex pipiens; none tested positive for the viruses. From 2008 to 2011, 946,213 mosquitoes, sampled between May and October, were tested; 86.5% were Cx. pipiens. West Nile virus was detected in 32 Cx. pipiens pools, and Usutu virus was detected in 229 mosquito pools (217 Cx. pipiens, 10 Aedes albopictus, one Anopheles maculipennis s.l., and one Aedes caspius). From 2009 to 2011, of 4,546 birds collected, 42 tested positive for West Nile virus and 48 for Usutu virus. West Nile virus and Usutu virus showed different patterns of activity during the 2008-2011 surveillance period. West Nile virus was detected in 2008, 2009, and 2010, but not in 2011. Usutu virus, however, was continuously active throughout 2009, 2010, and 2011. The data strongly suggest that both viruses overwinter in the surveyed area rather than being continually reintroduced every season. The lack of hibernating mosquitoes testing positive for the viruses and the presence of positive birds sampled early in the season support the hypothesis that the viruses overwinter in birds rather than in mosquitoes. Herd immunity in key bird species could explain the decline of West Nile virus observed in 2011, while the persistence of Usutu virus may be explained by not yet identified reservoirs. Reported results are comparable with a peri-Mediterranean circulation of the West Nile virus lineage 1 related strain, which became undetectable in the environment after two to three years of obvious circulation.

PERSISTENCE OF HAPTEN-ANTIBODY COMPLEXES IN THE CIRCULATION OF IMMUNIZED ANIMALS AFTER A SINGLE INTRAVENOUS INJECTION OF HAPTEN

PubMed Central

Schmidt, Donald H.; Kaufman, Bette M.; Butler, Vincent P.

1974-01-01

To study the fate of a low molecular weight antigen (hapten) in the circulation of animals whose sera contain antibodies specific for that low molecular weight antigen, a single injection of digoxin-3H (0.4 mg/kg) was administered intravenously to 18 rabbits. Thirteen animals (nine nonimmunized and four immunized with bovine serum albumin) served as control animals. In five rabbits which had been immunized with a digoxin-bovine serum albumin conjugate and whose sera contained digoxin-specific antibodies, the mean 12-h serum digoxin concentration was 8,300 ng/ml (control: 92 ng/ml) and the mean serum concentration 12 mo after the single injection of digoxin-3H was 85 ng/ml. In digoxin-immunized rabbits, less than 10% of the digoxin-3H was excreted in the first 10 days (control: 77% recovered in urine and feces) and the mean biological half-life of digoxin, as calculated from serum digoxin-3H disappearance curves, was 72 days (control: 3.4 days). In sera of digoxin-immunized rabbits, more than 90% of the circulating digoxin-3H was immunoglobulin bound, as determined by the double-antibody and dextran-coated charcoal methods. The serum disappearance rate of 125I-antidigoxin antibodies was similar in nonimmunized and in immunized animals and in the presence or absence of digoxin. It is concluded that the biological half-life of a hapten may be markedly prolonged when the hapten is bound to specific antibody. The persistence of antibody-hapten complexes in the circulation suggests that these complexes may not be deposited in tissues and raises the possibility that low molecular weight determinants may be capable of preventing or reversing the deposition of immune complexes, containing macromolecular antigens, in the tissues of experimental animals and man. PMID:4129823

A Study of Permeability Changes Due to Cold Fluid Circulation in Fractured Geothermal Reservoirs.

PubMed

Gholizadeh Doonechaly, Nima; Abdel Azim, Reda R; Rahman, Sheik S

2016-05-01

Reservoir behavior due to injection and circulation of cold fluid is studied with a shear displacement model based on the distributed dislocation technique, in a poro-thermoelastic environment. The approach is applied to a selected volume of Soultz geothermal reservoir at a depth range of 3600 to 3700 m. Permeability enhancement and geothermal potential of Soultz geothermal reservoir are assessed over a stimulation period of 3 months and a fluid circulation period of 14 years. This study-by shedding light onto another source of uncertainty-points toward a special role for the fracture surface asperities in predicting the shear dilation of fractures. It was also observed that thermal stress has a significant impact on changing the reservoir stress field. The effect of thermal stresses on reservoir behavior is more evident over longer circulation term as the rock matrix temperature is significantly lowered. Change in the fracture permeability due to the thermal stresses can also lead to the short circuiting between the injection and production wells which in turn decreases the produced fluid temperature significantly. The effect of thermal stress persists during the whole circulation period as it has significant impact on the continuous increase in the flow rate due to improved permeability over the circulation period. In the current study, taking into account the thermal stress resulted in a decrease of about 7 °C in predicted produced fluid temperature after 14 years of cold fluid circulation; a difference which notably influences the potential prediction of an enhanced geothermal system. © 2015, National Ground Water Association.

Impact of p53 status on heavy-ion radiation-induced micronuclei in circulating erythrocytes

NASA Technical Reports Server (NTRS)

Chang, P. Y.; Torous, D.; Lutze-Mann, L.; Winegar, R.

2000-01-01

Transgenic mice that differed in their p53 genetic status were exposed to an acute dose of highly charged and energetic (HZE) iron particle radiation. Micronuclei (MN) in two distinct populations of circulating peripheral blood erythrocytes, the immature reticulocytes (RETs) and the mature normochromatic erythrocytes (NCEs), were measured using a simple and efficient flow cytometric procedure. Our results show significant elevation in the frequency of micronucleated RETs (%MN-RETs) at 2 and 3 days post-radiation. At 3 days post-irradiation, the magnitude of the radiation-induced MN-RET was 2.3-fold higher in the irradiated p53 wild-type animals compared to the unirradiated controls, 2.5-fold higher in the p53 hemizygotes and 4.3-fold higher in the p53 nullizygotes. The persistence of this radiation-induced elevation of MN-RETs is dependent on the p53 genetic background of the animal. In the p53 wild-type and p53 hemizygotes, %MN-RETs returned to control levels by 9 days post-radiation. However, elevated levels of %MN-RETs in p53 nullizygous mice persisted beyond 56 days post-radiation. We also observed elevated MN-NCEs in the peripheral circulation after radiation, but the changes in radiation-induced levels of MN-NCEs appear dampened compared to those of the MN-RETs for all three strains of animals. These results suggest that the lack of p53 gene function may play a role in the iron particle radiation-induced genomic instability in stem cell populations in the hematopoietic system.

Venezuelan Equine Encephalitis Virus Infection of Spiny Rats

PubMed Central

Carrara, Anne-Sophie; Gonzales, Marta; Ferro, Cristina; Tamayo, Margarita; Aronson, Judith; Paessler, Slobodan; Anishchenko, Michael; Boshell, Jorge

2005-01-01

Enzootic strains of Venezuelan equine encephalitis virus (VEEV) circulate in forested habitats of Mexico, Central, and South America, and spiny rats (Proechimys spp.) are believed to be the principal reservoir hosts in several foci. To better understand the host-pathogen interactions and resistance to disease characteristic of many reservoir hosts, we performed experimental infections of F1 progeny from Proechimys chrysaeolus collected at a Colombian enzootic VEEV focus using sympatric and allopatric virus strains. All animals became viremic with a mean peak titer of 3.3 log10 PFU/mL, and all seroconverted with antibody titers from 1:20 to 1:640, which persisted up to 15 months. No signs of disease were observed, including after intracerebral injections. The lack of detectable disease and limited histopathologic lesions in these animals contrast dramatically with the severe disease and histopathologic findings observed in other laboratory rodents and humans, and support their role as reservoir hosts with a long-term coevolutionary relationship to VEEV. PMID:15890116

The transcriptional programme of the androgen receptor (AR) in prostate cancer.

PubMed

Lamb, Alastair D; Massie, Charlie E; Neal, David E

2014-03-01

The androgen receptor (AR) is essential for normal prostate and prostate cancer cell growth. AR transcriptional activity is almost always maintained even in hormone relapsed prostate cancer (HRPC) in the absence of normal levels of circulating testosterone. Current molecular techniques, such as chromatin-immunoprecipitation sequencing (ChIP-seq), have permitted identification of direct AR-binding sites in cell lines and human tissue with a distinct coordinate network evident in HRPC. The effectiveness of novel agents, such as abiraterone acetate (suppresses adrenal androgens) or enzalutamide (MDV3100, potent AR antagonist), in treating advanced prostate cancer underlines the on-going critical role of the AR throughout all stages of the disease. Persistent AR activity in advanced disease regulates cell cycle activity, steroid biosynthesis and anabolic metabolism in conjunction with regulatory co-factors, such as the E2F family, c-Myc and signal transducer and activator of transcription (STAT) transcription factors. Further treatment approaches must target these other factors. © 2013 The Authors. BJU International © 2013 BJU International.

Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer.

PubMed

Buchlis, George; Podsakoff, Gregory M; Radu, Antonetta; Hawk, Sarah M; Flake, Alan W; Mingozzi, Federico; High, Katherine A

2012-03-29

In previous work we transferred a human factor IX-encoding adeno-associated viral vector (AAV) into skeletal muscle of men with severe hemophilia B. Biopsy of injected muscle up to 1 year after vector injection showed evidence of gene transfer by Southern blot and of protein expression by IHC and immunofluorescent staining. Although the procedure appeared safe, circulating F.IX levels remained subtherapeutic (< 1%). Recently, we obtained muscle tissue from a subject injected 10 years earlier who died of causes unrelated to gene transfer. Using Western blot, IHC, and immunofluorescent staining, we show persistent factor IX expression in injected muscle tissue. F.IX transcripts were detected in injected skeletal muscle using RT-PCR, and isolated whole genomic DNA tested positive for the presence of the transferred AAV vector sequence. This is the longest reported transgene expression to date from a parenterally administered AAV vector, with broad implications for the future of muscle-directed gene transfer.

Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer

PubMed Central

Buchlis, George; Podsakoff, Gregory M.; Radu, Antonetta; Hawk, Sarah M.; Flake, Alan W.; Mingozzi, Federico

2012-01-01

In previous work we transferred a human factor IX–encoding adeno-associated viral vector (AAV) into skeletal muscle of men with severe hemophilia B. Biopsy of injected muscle up to 1 year after vector injection showed evidence of gene transfer by Southern blot and of protein expression by IHC and immunofluorescent staining. Although the procedure appeared safe, circulating F.IX levels remained subtherapeutic (< 1%). Recently, we obtained muscle tissue from a subject injected 10 years earlier who died of causes unrelated to gene transfer. Using Western blot, IHC, and immunofluorescent staining, we show persistent factor IX expression in injected muscle tissue. F.IX transcripts were detected in injected skeletal muscle using RT-PCR, and isolated whole genomic DNA tested positive for the presence of the transferred AAV vector sequence. This is the longest reported transgene expression to date from a parenterally administered AAV vector, with broad implications for the future of muscle-directed gene transfer. PMID:22271447

Epstein-Barr Virus (EBV) DNA in plasma is not encapsidated in patients with EBV-related malignancies.

PubMed

Ryan, Julie L; Fan, Hongxin; Swinnen, Lode J; Schichman, Steven A; Raab-Traub, Nancy; Covington, Mary; Elmore, Sandra; Gulley, Margaret L

2004-06-01

Epstein-Barr Virus (EBV), a ubiquitous gamma herpes virus, infects more than 95% of the human population before adulthood. Life-long persistence, usually without adverse health consequences, relies on a balance between viral latency, viral replication, and host immune response. Patients with EBV-related disease often have high levels of EBV DNA in their plasma. This study addresses whether this circulating, cell-free EBV DNA is encapsidated in virions or exists as naked genomes. First, an assay was developed, combining DNase I and quantitative real-time PCR, to discriminate encapsidated from naked EBV DNA. EBV DNA was almost always naked in the plasma of AIDS-related lymphoma patients (n = 11) and immunosuppressed/posttransplantation patients (n = 8). In contrast, infectious mononucleosis patients (n = 30) often had a mixture of encapsidated and naked EBV DNA. These findings may be important in understanding how viral load relates to disease status and in predicting response to nucleoside analogs and other antiviral therapies.

Neutrophil kinetics of recombinant human granulocyte colony-stimulating factor-induced neutropenia in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okada, Yuji; Kawagishi, Mayumi; Kusaka, Masaru

Single injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF) immediately induced a decrease in the number of circulating neutrophils in rats. This neutropenia occurred 10 minutes after the injection but disappeared 40 minutes after injection. This transient neutropenia was dose-dependently induced by rhG-CSF and also induced by repeated injections. We studied the kinetics of circulating neutrophils in transient neutropenia. rhG-CSF markedly decreased the number of {sup 3}H-diisopropylfluorophosphate ({sup 3}H-DFP) labeled neutrophils in the circulation 10 minutes after injection but the labeled neutrophils recovered to near the control level 40 minutes after the injection. These results indicate that the neutrophil marginationmore » accounts for the neutrophenia and the marginated neutrophils return to the circulation.« less

Circulating factors induce coronary endothelial cell activation following exposure to inhaled diesel exhaust and nitrogen dioxide in humans: Evidence from a novel translational in vitro model**

EPA Science Inventory

The vascular toxicity of inhaled agents may be caused by soluble factors that are released into the systemic circulation. To confirm this in a straightforward manner, we obtained plasma from healthy human volunteers before and after exposure to diesel exhaust (DE) and nitrogen di...

Surveillance for influenza virus subtypes H1, H2 and H3 among wild birds in Ukraine in 2006-2012

USDA-ARS?s Scientific Manuscript database

Background: Influenza is one of the most important and unpredictable diseases of humans, other mammals and birds. Influenza virus of H1, H2, and H3 subtypes circulate in humans and cause seasonal influenza. Similar subtypes are also circulating in the natural reservoir, wild aquatic birds, and und...

Persistent positive North Atlantic oscillation mode dominated the Medieval Climate Anomaly.

PubMed

Trouet, Valérie; Esper, Jan; Graham, Nicholas E; Baker, Andy; Scourse, James D; Frank, David C

2009-04-03

The Medieval Climate Anomaly (MCA) was the most recent pre-industrial era warm interval of European climate, yet its driving mechanisms remain uncertain. We present here a 947-year-long multidecadal North Atlantic Oscillation (NAO) reconstruction and find a persistent positive NAO during the MCA. Supplementary reconstructions based on climate model results and proxy data indicate a clear shift to weaker NAO conditions into the Little Ice Age (LIA). Globally distributed proxy data suggest that this NAO shift is one aspect of a global MCA-LIA climate transition that probably was coupled to prevailing La Niña-like conditions amplified by an intensified Atlantic meridional overturning circulation during the MCA.

Soil moisture and the persistence of North American drought

NASA Technical Reports Server (NTRS)

Oglesby, Robert J.; Erickson, David J., III

1989-01-01

Numerical sensitivity experiments on the effects of soil moisture on North American summertime climate are performed using a 12-layer global atmospheric general circulation model. Consideration is given to the hypothesis that reduced soil moisture may induce and amplify warm, dry summers of midlatitude continental interiors. The simulations resemble the conditions of the summer of 1988, including an extensive drought over much of North America. It is found that a reduction in soil moisture leads to an increase in surface temperature, lower surface pressure, increased ridging aloft, and a northward shift of the jet stream. It is shown that low-level moisture advection from the Gulf of Mexico is important in the maintenance of persistent soil moisture deficits.

Central role of a bacterial two-component gene regulatory system of previously unknown function in pathogen persistence in human saliva.

PubMed

Shelburne, Samuel A; Sumby, Paul; Sitkiewicz, Izabela; Granville, Chanel; DeLeo, Frank R; Musser, James M

2005-11-01

The molecular genetic mechanisms used by bacteria to persist in humans are poorly understood. Group A Streptococcus (GAS) causes the majority of bacterial pharyngitis cases in humans and is prone to persistently inhabit the upper respiratory tract. To gain information about how GAS survives in and infects the oropharynx, we analyzed the transcriptome of a serotype M1 strain grown in saliva. The dynamic pattern of changes in transcripts of genes [spy0874/0875, herein named sptR and sptS (sptR/S), for saliva persistence] encoding a two-component gene regulatory system of unknown function suggested that SptR/S contributed to persistence of GAS in saliva. Consistent with this idea, an isogenic nonpolar mutant strain (DeltasptR) was dramatically less able to survive in saliva compared with the parental strain. Iterative expression microarray analysis of bacteria grown in saliva revealed that transcripts of several known and putative GAS virulence factor genes were decreased significantly in the DeltasptR mutant strain. Compared with the parental strain, the isogenic mutant strain also had altered transcripts of multiple genes encoding proteins involved in complex carbohydrate acquisition and utilization pathways. Western immunoblot analysis and real-time PCR analysis of GAS in throat swabs taken from humans with pharyngitis confirmed the findings. We conclude that SptR/S optimizes persistence of GAS in human saliva, apparently by strategically influencing metabolic pathways and virulence factor production. The discovery of a genetic program that significantly increased persistence of a major human pathogen in saliva enhances understanding of how bacteria survive in the host and suggests new therapeutic strategies.

A role of low dose chemical mixtures in adipose tissue in carcinogenesis.

PubMed

Lee, Duk-Hee; Jacobs, David R; Park, Ho Yong; Carpenter, David O

2017-11-01

The Halifax project recently hypothesized a composite carcinogenic potential of the mixture of low dose chemicals which are commonly encountered environmentally, yet which are not classified as human carcinogens. A long neglected but important fact is that adipose tissue is an important exposure source for chemical mixtures. In fact, findings from human studies based on several persistent organic pollutants in general populations with only background exposure should be interpreted from the viewpoint of chemical mixtures because serum concentrations of these chemicals can be seen as surrogates for chemical mixtures in adipose tissue. Furthermore, in conditions such as obesity with dysfunctional adipocytes or weight loss in which lipolysis is increased, the amount of the chemical mixture released from adipose tissue to circulation is increased. Thus, both obesity and weight loss can enhance the chance of chemical mixtures reaching critical organs, however paradoxical this idea may be when fat mass is the only factor considered. The complicated, interrelated dynamics of adipocytes and chemical mixtures can explain puzzling findings related to body weight among cancer patients, including the obesity paradox. The contamination of fat in human diet with chemical mixtures, occurring for reasons similar to contamination of human adipose tissue, may be a missing factor which affects the association between dietary fat intake and cancer. The presence of chemical mixtures in adipose tissue should be considered in future cancer research, including clinical trials on weight management among cancer survivors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Determination of Leptospira borgpetersenii serovar Javanica and Leptospira interrogans serovar Bataviae as the persistent Leptospira serovars circulating in the urban rat populations in Peninsular Malaysia.

PubMed

Benacer, Douadi; Mohd Zain, Siti Nursheena; Sim, Shin Zhu; Mohd Khalid, Mohd Khairul Nizam; Galloway, Renee L; Souris, Marc; Thong, Kwai Lin

2016-03-01

Leptospirosis is an emerging infectious disease of global significance, and is endemic in tropical countries, including Malaysia. Over the last decade, a dramatic increase of human cases was reported; however, information on the primary vector, the rat, and the Leptospira serovars circulating among the rat population is limited. Therefore, the present study was undertaken to isolate Leptospira and characterise the serovars circulating in the urban rat populations from selected main cities in Peninsular Malaysia. Rat trappings were carried out between October 2011 to February 2014 in five urban cities which were chosen as study sites to represent different geographical locations in Peninsular Malaysia. Microscopic agglutination test (MAT) and PCR were carried out to identify the Leptospiral serogroup and determine the pathogenic status of the isolates, respectively while pulsed-field gel electrophoresis (PFGE) and random amplified polymorphic DNA (RAPD)-PCR were used to characterize the isolates. Three rat species were identified from the three hundred and fifty seven rats captured with Rattus rattus, being the dominant rat species (285, 80 %) followed by Rattus norgevicus (53, 15 %) and Rattus exulans (19, 5 %). Only 39 samples (11.0 %) were positive by culture and further confirmed as pathogenic Leptospira by PCR. Significant associations were shown between host infection with locality, season, host-age and species. Based on MAT, two serogroups were identified in the population namely; L. borgpetersenii serogroup Javanica (n = 16) and L. interrogans serogroup Bataviae (n = 23). Pulsed-field gel electrophoresis (PFGE) distinguished the two serovars in the urban rat populations: L. borgpetersenii serovar Javanica (41 %), and L. interrogans serovar Bataviae (59 %). RAPD-PCR yielded 14 distinct patterns and was found to be more discriminative than PFGE. This study confirms two Leptospira serovars circulating among the urban rats population in Peninsular Malaysia namely; L. borgpetersenii serovar Javanica and L. interrogans serovars Bataviae. Despite the low number of isolates obtained from the rat population, this study suggests that rodent control programs and disease surveillance may help to reduce the possible risk of disease transmission.

Modelling the role of Tax expression in HTLV-I persistence in vivo.

PubMed

Li, Michael Y; Lim, Aaron G

2011-12-01

Human T-lymphotropic virus type I (HTLV-I) is a persistent human retrovirus characterized by life-long infection and risk of developing HAM/TSP, a progressive neurological and inflammatory disease, and adult T-cell leukemia (ATL). Chronically infected individuals often harbor high proviral loads despite maintaining a persistently activated immune response. Based on a new hypothesis for the persistence of HTLV-I infection, a three-dimensional compartmental model is constructed that describes the dynamic interactions among latently infected target cells, target-cell activation, and immune responses to HTLV-I, with an emphasis on understanding the role of Tax expression in the persistence of HTLV-I.

In vitro microfluidic circulatory system for circulating cancer cells

PubMed Central

wan, jiandi; Fan, Rong; Emery, Travis; Zhang, Yongguo; Xia, Yuxuan; Sun, Jun; Wan, Jiandi

2016-01-01

Circulating tumor cells (CTCs) experience hemodynamic shear stress in circulation and play critical roles in cancer metastasis. The effect of shear on CTCs, however, remains less studied. Here, we described a protocol to circulate HCT116 human colon cancer cells in a microfluidic circulatory system mimicking physiologically relevant circulating conditions. This protocol represents a useful scaffold to mimic the transportation of CTCs in circulation and thus provides an effective means to study the effect of shear on CTCs. We anticipate that future studies using the developed system will help us to further investigate the regulatory roles of shear in molecular responses of CTCs. PMID:28690779

Distribution of Bartonella henselae Variants in Patients, Reservoir Hosts and Vectors in Spain

PubMed Central

Gil, Horacio; Escudero, Raquel; Pons, Inmaculada; Rodríguez-Vargas, Manuela; García-Esteban, Coral; Rodríguez-Moreno, Isabel; García-Amil, Cristina; Lobo, Bruno; Valcárcel, Félix; Pérez, Azucena; Jiménez, Santos; Jado, Isabel; Juste, Ramón; Segura, Ferrán; Anda, Pedro

2013-01-01

We have studied the diversity of B. henselae circulating in patients, reservoir hosts and vectors in Spain. In total, we have fully characterized 53 clinical samples from 46 patients, as well as 78 B. henselae isolates obtained from 35 cats from La Rioja and Catalonia (northeastern Spain), four positive cat blood samples from which no isolates were obtained, and three positive fleas by Multiple Locus Sequence Typing and Multiple Locus Variable Number Tandem Repeats Analysis. This study represents the largest series of human cases characterized with these methods, with 10 different sequence types and 41 MLVA profiles. Two of the sequence types and 35 of the profiles were not described previously. Most of the B. henselae variants belonged to ST5. Also, we have identified a common profile (72) which is well distributed in Spain and was found to persist over time. Indeed, this profile seems to be the origin from which most of the variants identified in this study have been generated. In addition, ST5, ST6 and ST9 were found associated with felines, whereas ST1, ST5 and ST8 were the most frequent sequence types found infecting humans. Interestingly, some of the feline associated variants never found on patients were located in a separate clade, which could represent a group of strains less pathogenic for humans. PMID:23874563

Differences in problem-solving between canid populations: Do domestication and lifetime experience affect persistence?

PubMed

Brubaker, Lauren; Dasgupta, Sandipan; Bhattacharjee, Debottam; Bhadra, Anindita; Udell, Monique A R

2017-07-01

Past research has suggested that a variety of factors, phylogenetic and ontogenetic, play a role in how canines behave during problem-solving tasks and the degree to which the presence of a human influences their problem-solving behaviour. While comparisons between socialized wolves and domestic dogs have commonly been used to tease apart these predictive factors, in many cases a single dog population, often pets, have been used for these comparisons. Less is understood about how different populations of dogs may behave when compared with wolves, or with each other, during an independent problem-solving task. This experiment compared the independent persistence of four populations of canines (two groups of pet domestic dogs, a group of free-ranging domestic dogs, and human-socialized wolves) on an independent problem-solving task in the presence of an on looking human. Results showed that wolves persisted the most at the task while free-ranging dogs persisted the least. Free-ranging dogs gazed at the human experimenter for the longest durations during the task. While further research is needed to understand why these differences exist, this study demonstrates that dogs, even those living outside human homes as scavengers, show comparatively low levels of persistence when confronted with a solvable task in the presence of a human as well as significantly greater duration of human-directed gaze when compared with wolves.

Cell–specific Variation in E-selectin Ligand Expression Among Human Peripheral Blood Mononuclear Cells: Implications for Immunosurveillance and Pathobiology

PubMed Central

Silva, Mariana; Fung, Ronald Kam Fai; Donnelly, Conor Brian; Videira, Paula Alexandra; Sackstein, Robert

2017-01-01

Both host defense and immunopathology are shaped by the ordered recruitment of circulating leukocytes to affected sites, a process initiated by binding of blood-borne cells to E-selectin displayed at target endothelial beds. Accordingly, knowledge of the expression and function of leukocyte E-selectin ligands is key to understanding the tempo and specificity of immunoreactivity. Here, we performed E-selectin adherence assays under hemodynamic flow conditions coupled with flow cytometry and western blot analysis to elucidate the function and structural biology of glycoprotein E-selectin ligands expressed on human peripheral blood mononuclear cells (PBMCs). Circulating monocytes uniformly express high levels of the canonical E-selectin binding determinant sLeX and display markedly greater adhesive interactions with E-selectin than do circulating lymphocytes, which exhibit variable E-selectin binding among CD4+ and CD8+ T-cells but no binding by B-cells. Monocytes prominently present sLeX decorations on an array of protein scaffolds including PSGL-1, CD43, and CD44 (rendering the E-selectin ligands CLA, CD43E, and HCELL, respectively), and B-cells altogether lack E-selectin ligands. Quantitative PCR gene expression studies of glycosyltransferases that regulate display of sLeX reveal high transcript levels among circulating monocytes and low levels among circulating B-cells, and, commensurately, cell surface α(1,3)-fucosylation reveals that acceptor sialyllactosaminyl glycans convertible into sLeX are abundantly expressed on human monocytes yet are relatively deficient on B-cells. Collectively, these findings unveil distinct cell-specific patterns of E-selectin ligand expression among human PBMCs, indicating that circulating monocytes are specialized to engage E-selectin and providing key insights into the molecular effectors mediating recruitment of these cells at inflammatory sites. PMID:28330896

Effects and mechanisms of action of sildenafil citrate in human chorionic arteries

PubMed Central

Maharaj, Chrisen H; O'Toole, Daniel; Lynch, Tadhg; Carney, John; Jarman, James; Higgins, Brendan D; Morrison, John J; Laffey, John G

2009-01-01

Objectives Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. Study Design Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. Results Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. Conclusion Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO. PMID:19389232

Melanin-concentrating hormone in peripheral circulation in the human.

PubMed

Naufahu, J; Alzaid, F; Fiuza Brito, M; Doslikova, B; Valencia, T; Cunliffe, A; Murray, J F

2017-03-01

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a well-characterised role in energy homeostasis and emergent roles in diverse physiologic functions such as arousal, mood and reproduction. Work to date has predominantly focused on its hypothalamic functions using animal models; however, little attention has been paid to its role in circulation in humans. The aims of this study were to (a) develop a radioimmunoassay for the detection of MCH in human plasma; (b) establish reference ranges for circulating MCH and (c) characterise the pattern of expression of circulating MCH in humans. A sensitive and specific RIA was developed and cross-validated by RP-HPLC and MS. The effective range was 19.5-1248 pg MCH/mL. Blood samples from 231 subjects were taken to establish a reference range of 19.5-55.4 pg/mL for fasting MCH concentrations. There were no significant differences between male and female fasting MCH concentrations; however, there were correlations between MCH concentrations and BMI in males and females with excess fat (P < 0.001 and P = 0.020) and between MCH concentrations and fat mass in females with excess fat (P = 0.038). Plasma MCH concentrations rose significantly after feeding in a group of older individuals (n = 50, males P = 0.006, females P = 0.023). There were no robust significant correlations between fasting or post-prandial MCH and resting metabolic rate, plasma glucose, insulin or leptin concentrations although there were correlations between circulating MCH and leptin concentrations in older individuals (P = 0.029). These results indicate that the role of circulating MCH may not be reflective of its regulatory hypothalamic role. © 2017 Society for Endocrinology.

Twitter web-service for soft agent reporting in persistent surveillance systems

NASA Astrophysics Data System (ADS)

Rababaah, Haroun; Shirkhodaie, Amir

2010-04-01

Persistent surveillance is an intricate process requiring monitoring, gathering, processing, tracking, and characterization of many spatiotemporal events occurring concurrently. Data associated with events can be readily attained by networking of hard (physical) sensors. Sensors may have homogeneous or heterogeneous (hybrid) sensing modalities with different communication bandwidth requirements. Complimentary to hard sensors are human observers or "soft sensors" that can report occurrences of evolving events via different communication devices (e.g., texting, cell phones, emails, instant messaging, etc.) to the command control center. However, networking of human observers in ad-hoc way is rather a difficult task. In this paper, we present a Twitter web-service for soft agent reporting in persistent surveillance systems (called Web-STARS). The objective of this web-service is to aggregate multi-source human observations in hybrid sensor networks rapidly. With availability of Twitter social network, such a human networking concept can not only be realized for large scale persistent surveillance systems (PSS), but also, it can be employed with proper interfaces to expedite rapid events reporting by human observers. The proposed technique is particularly suitable for large-scale persistent surveillance systems with distributed soft and hard sensor networks. The efficiency and effectiveness of the proposed technique is measured experimentally by conducting several simulated persistent surveillance scenarios. It is demonstrated that by fusion of information from hard and soft agents improves understanding of common operating picture and enhances situational awareness.

Persistent Hall voltages across thin planar charged quantum rings on the surface of a topological insulator

NASA Astrophysics Data System (ADS)

Durganandini, P.

2015-03-01

We consider thin planar charged quantum rings on the surface of a three dimensional topological insulator coated with a thin ferromagnetic layer. We show theoretically, that when the ring is threaded by a magnetic field, then, due to the Aharanov-Bohm effect, there are not only the well known circulating persistent currents in the ring but also oscillating persistent Hall voltages across the thin ring. Such oscillating persistent Hall voltages arise due to the topological magneto-electric effect associated with the axion electrodynamics exhibited by the surface electronic states of the three dimensional topological insulator when time reversal symmetry is broken. We further generalize to the case of dipole currents and show that analogous Hall dipole voltages arise. We also discuss the robustness of the effect and suggest possible experimental realizations in quantum rings made of semiconductor heterostructures. Such experiments could also provide new ways of observing the predicted topological magneto-electric effect in three dimensional topological insulators with time reversal symmetry breaking. I thank BCUD, Pune University, Pune for financial support through research grant.

Plants and Photosynthesis: Level III, Unit 3, Lesson 1; The Human Digestive System: Lesson 2; Functions of the Blood: Lesson 3; Human Circulation and Respiration: Lesson 4; Reproduction of a Single Cell: Lesson 5; Reproduction by Male and Female Cells: Lesson 6; The Human Reproductive System: Lesson 7; Genetics and Heredity: Lesson 8; The Nervous System: Lesson 9; The Glandular System: Lesson 10. Advanced General Education Program. A High School Self-Study Program.

ERIC Educational Resources Information Center

Manpower Administration (DOL), Washington, DC. Job Corps.

This self-study program for the high-school level contains lessons in the following subjects: Plants and Photosynthesis; The Human Digestive System; Functions of the Blood; Human Circulation and Respiration; Reproduction of a Single Cell; Reproduction by Male and Female Cells; The Human Reproductive System; Genetics and Heredity; The Nervous…

Computational Characterization of Exogenous MicroRNAs that Can Be Transferred into Human Circulation

PubMed Central

Shu, Jiang; Chiang, Kevin; Zempleni, Janos; Cui, Juan

2015-01-01

MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs. Specifically, we analyzed all publicly available microRNAs, a total of 34,612 from 194 species, with 1,102 features derived from the microRNA sequence and structure. Through in-depth bioinformatics analysis, 8 groups of discriminative features have been used to characterize human circulating microRNAs and infer the likelihood that a microRNA will get transferred into human circulation. For example, 345 dietary microRNAs have been predicted as highly transportable candidates where 117 of them have identical sequences with their homologs in human and 73 are known to be associated with exosomes. Through a milk feeding experiment, we have validated 9 cow-milk microRNAs in human plasma using microRNA-sequencing analysis, including the top ranked microRNAs such as bta-miR-487b, miR-181b, and miR-421. The implications in health-related processes have been illustrated in the functional analysis. This work demonstrates the data-driven computational analysis is highly promising to study novel molecular characteristics of transportable microRNAs while bypassing the complex mechanistic details. PMID:26528912

Computational Characterization of Exogenous MicroRNAs that Can Be Transferred into Human Circulation.

PubMed

Shu, Jiang; Chiang, Kevin; Zempleni, Janos; Cui, Juan

2015-01-01

MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs. Specifically, we analyzed all publicly available microRNAs, a total of 34,612 from 194 species, with 1,102 features derived from the microRNA sequence and structure. Through in-depth bioinformatics analysis, 8 groups of discriminative features have been used to characterize human circulating microRNAs and infer the likelihood that a microRNA will get transferred into human circulation. For example, 345 dietary microRNAs have been predicted as highly transportable candidates where 117 of them have identical sequences with their homologs in human and 73 are known to be associated with exosomes. Through a milk feeding experiment, we have validated 9 cow-milk microRNAs in human plasma using microRNA-sequencing analysis, including the top ranked microRNAs such as bta-miR-487b, miR-181b, and miR-421. The implications in health-related processes have been illustrated in the functional analysis. This work demonstrates the data-driven computational analysis is highly promising to study novel molecular characteristics of transportable microRNAs while bypassing the complex mechanistic details.

Prolonged effect of the stratospheric pathway in linking Barents-Kara Sea sea ice variability to the midlatitude circulation in a simplified model

NASA Astrophysics Data System (ADS)

Zhang, Pengfei; Wu, Yutian; Smith, Karen L.

2018-01-01

To better understand the dynamical mechanism that accounts for the observed lead-lag correlation between the early winter Barents-Kara Sea (BKS) sea ice variability and the later winter midlatitude circulation response, a series of experiments are conducted using a simplified atmospheric general circulation model with a prescribed idealized near-surface heating over the BKS. A prolonged effect is found in the idealized experiments following the near-surface heating and can be explicitly attributed to the stratospheric pathway and the long time scale in the stratosphere. The analysis of the Eliassen-Palm flux shows that, as a result of the imposed heating and linear constructive interference, anomalous upward propagating planetary-scale waves are excited and weaken the stratospheric polar vortex. This stratospheric response persists for approximately 1-2 months accompanied by downward migration to the troposphere and the surface. This downward migration largely amplifies and extends the low-level jet deceleration in the midlatitudes and cold air advection over central Asia. The idealized model experiments also suggest that the BKS region is the most effective in affecting the midlatitude circulation than other regions over the Arctic.

Eomeshi NK Cells in Human Liver Are Long-Lived and Do Not Recirculate but Can Be Replenished from the Circulation

PubMed Central

Cuff, Antonia O.; Robertson, Francis P.; Stegmann, Kerstin A.; Pallett, Laura J.; Maini, Mala K.; Davidson, Brian R.

2016-01-01

Human liver contains an Eomeshi population of NK cells that is not present in the blood. In this study, we show that these cells are characterized by a molecular signature that mediates their retention in the liver. By examining liver transplants where donors and recipients are HLA mismatched, we distinguish between donor liver–derived and recipient-derived leukocytes to show that Eomeslo NK cells circulate freely whereas Eomeshi NK cells are unable to leave the liver. Furthermore, Eomeshi NK cells are retained in the liver for up to 13 y. Therefore, Eomeshi NK cells are long-lived liver-resident cells. We go on to show that Eomeshi NK cells can be recruited from the circulation during adult life and that circulating Eomeslo NK cells are able to upregulate Eomes and molecules mediating liver retention under cytokine conditions similar to those in the liver. This suggests that circulating NK cells are a precursor of their liver-resident counterparts. PMID:27798170

CIRCULATING CD11B EXPRESSION CORRELATES WITH THE NEUTROPHIL RESPONSE AND AIRWAY MCD-14 EXPRESSION IS ENHANCED FOLLOWING OZONE EXPOSURE IN HUMANS

EPA Science Inventory

We recently reported that baseline expression of circulating CD11b is associated with the magnitude of the neutrophil response following inhaled endotoxin. In this study, we examined whether circulating CD11b plays a similar role in the inflammatory response following inhaled ozo...

Basophil degranulation induced by oral poison ivy antigen.

PubMed

Shelley, W B; Resnik, S S

1965-08-01

Seven subjects shown by patch test to be sensitive to poison ivy oleoresin were challenged with graded oral doses of ivy extract. In each instance the circulating basophil leukocytes showed significant degranulation within one hour of challenge. This finding was interpreted as evidence of the presence of immediate-type circulating antibody to ivy antigen in these subjects. No drop in the absolute basophil count was noted, but with higher oral doses the degranulation persisted for several days. Thirteen control subjects showed no change in the basophil morphology or count, indicating that the resin at these levels was not toxic to this cell. All but one of the sensitive subjects showed objective patch test evidence of hyposensitization following the intensive three-week course of oral poison ivy antigen.

Changes in atmospheric circulation patterns affect midcontinent wetlands sensitive to climate

USGS Publications Warehouse

LaBaugh, J.W.; Winter, T.C.; Swanson, G.A.; Rosenberry, D.

1996-01-01

Twenty-seven years of data from midcontinent wetlands indicate that the response of these wetlands to extremes in precipitation-drought and deluge-persists beyond the extreme events. Chemical changes transcend such simple relations as increased salinity during dry periods because drought provides mechanisms for removal of salt by deflation and seepage to groundwater. Inundation of vegetation zones including rooted or floating mats of cattail (Typha glauca) can stimulate sulfate reduction and shift the anion balance from sulfate to bicarbonate dominance. Disruptions in the circulation of moisture-laden air masses over the midcontinent, as in the drought of 1988 and the deluge of 1993, have a major effect on these wetlands, which are representatives of the primary waterfowl breeding habitat of the continent.

Hydro-meteorologic assessment of October 2015 extreme precipitation event on Santee Experimental Forest Watersheds, South Carolina

Treesearch

D.M. Amatya; C.A. Harrison; C.C. Trettin

2016-01-01

The extreme precipitation event on October 3-4, 2015, likely resulting from the convergence of a persistent deep easterly flow, the continuous supply of moisture, the terrain, and the circulation associated with Hurricane Joaquin off the eastern Atlantic Coast (http://cms.met.psu. edu/sref/severe/2015/04Oct2015.pdf) resulted in extreme and prolonged flooding in many...

Stabilization and Augmentation of Circulating AIM in Mice by Synthesized IgM-Fc

PubMed Central

Kai, Toshihiro; Yamazaki, Tomoko; Arai, Satoko; Miyazaki, Toru

2014-01-01

Owing to rapid and drastic changes in lifestyle and eating habits in modern society, obesity and obesity-associated diseases are among the most important public health problems. Hence, the development of therapeutic approaches to regulate obesity is strongly desired. In view of previous work showing that apoptosis inhibitor of macrophage (AIM) blocks lipid storage in adipocytes, thereby preventing obesity caused by a high-fat diet, we here explored a strategy to augment circulating AIM levels. We synthesized the Fc portion of the soluble human immunoglobulin (Ig)M heavy chain and found that it formed a pentamer containing IgJ as natural IgM does, and effectively associated with AIM in vitro. When we injected the synthesized Fc intravenously into mice lacking circulating IgM, it associated with endogenous mouse AIM, protecting AIM from renal excretion and preserving the circulating AIM levels. As the synthesized Fc lacked the antigen-recognizing variable region, it provoked no undesired immune response. In addition, a challenge with the Fc-human AIM complex in wild-type mice, which exhibited normal levels of circulating IgM and AIM, successfully maintained the levels of the human AIM in mouse blood. We also observed that the human AIM was effectively incorporated into adipocytes in visceral fat tissue, suggesting its functionality against obesity. Thus, our findings reveal potent strategies to safely increase AIM levels, which could form the basis for developing novel therapies for obesity. PMID:24804991

From Emergence to Eradication: The Epidemiology of Poliomyelitis Deconstructed

PubMed Central

Nathanson, Neal; Kew, Olen M.

2010-01-01

Poliomyelitis has appeared in epidemic form, become endemic on a global scale, and been reduced to near-elimination, all within the span of documented medical history. Epidemics of the disease appeared in the late 19th century in many European countries and North America, following which polio became a global disease with annual epidemics. During the period of its epidemicity, 1900–1950, the age distribution of poliomyelitis cases increased gradually. Beginning in 1955, the creation of poliovirus vaccines led to a stepwise reduction in poliomyelitis, culminating in the unpredicted elimination of wild polioviruses in the United States by 1972. Global expansion of polio immunization resulted in a reduction of paralytic disease from an estimated annual prevaccine level of at least 600,000 cases to fewer than 1,000 cases in 2000. Indigenous wild type 2 poliovirus was eradicated in 1999, but unbroken localized circulation of poliovirus types 1 and 3 continues in 4 countries in Asia and Africa. Current challenges to the final eradication of paralytic poliomyelitis include the continued transmission of wild polioviruses in endemic reservoirs, reinfection of polio-free areas, outbreaks due to circulating vaccine-derived polioviruses, and persistent excretion of vaccine-derived poliovirus by a few vaccinees with B-cell immunodeficiencies. Beyond the current efforts to eradicate the last remaining wild polioviruses, global eradication efforts must safely navigate through an unprecedented series of endgame challenges to assure the permanent cessation of all human poliovirus infections. PMID:20978089

Circulating factors induce coronary endothelial ceIl activation foIlowing exposure to inhaled diesel exhaust and nitrogen dioxide in humans :Evidence from a novel translational in vitro model

EPA Science Inventory

The vascular toxicity of inhaled agents may be caused by soluble factors that are released into the systemic circulation. To confirm this in a straightforward manner, we obtained plasma from healthy human volunteers before and after exposure to diesel exhaust (DE) and nitrogen di...

NK cell-released exosomes: Natural nanobullets against tumors.

PubMed

Fais, Stefano

2013-01-01

We have recently reported that human natural killer (NK) cells release exosomes that express both NK-cell markers and cytotoxic molecules. Similar results were obtained with circulating exosomes from human healthy donors. Both NK-cell derived and circulating exosomes exerted a full functional activity and killed both tumor and activated immune cells. These findings indicate that NK-cell derived exosomes might constitute a new promising therapeutic tool.

NK cell-released exosomes

PubMed Central

Fais, Stefano

2013-01-01

We have recently reported that human natural killer (NK) cells release exosomes that express both NK-cell markers and cytotoxic molecules. Similar results were obtained with circulating exosomes from human healthy donors. Both NK-cell derived and circulating exosomes exerted a full functional activity and killed both tumor and activated immune cells. These findings indicate that NK-cell derived exosomes might constitute a new promising therapeutic tool. PMID:23482694

Risk factors for persistent cervical intraepithelial neoplasia grades 1 and 2: managed by watchful waiting.

PubMed

Ho, Gloria Y F; Einstein, Mark H; Romney, Seymour L; Kadish, Anna S; Abadi, Maria; Mikhail, Magdy; Basu, Jayasri; Thysen, Benjamin; Reimers, Laura; Palan, Prabhudas R; Trim, Shelly; Soroudi, Nafisseh; Burk, Robert D

2011-10-01

: This study examines risk factors for persistent cervical intraepithelial neoplasia (CIN) and examines whether human papillomavirus (HPV) testing predicts persistent lesions. : Women with histologically diagnosed CIN 1 or CIN 2 (n = 206) were followed up every 3 months without treatment. Human papillomavirus genotyping, plasma levels of ascorbic acid, and red blood cell folate levels were obtained. Cervical biopsy at 12 months determined the presence of CIN. Relative risk (RR) was estimated by log-linked binomial regression models. : At 12 months, 70% of CIN 1 versus 54% of CIN 2 lesions spontaneously regressed (p < .001). Levels of folate or ascorbic acid were not associated with persistent CIN at 12 months. Compared with HPV-negative women, those with multiple HPV types (RRs ranged from 1.68 to 2.17 at each follow-up visit) or high-risk types (RRs range = 1.74-2.09) were at increased risk for persistent CIN; women with HPV-16/18 had the highest risk (RRs range = 1.91-2.21). Persistent infection with a high-risk type was also associated with persistent CIN (RRs range = 1.50-2.35). Typing for high-risk HPVs at 6 months only had a sensitivity of 46% in predicting persistence of any lesions at 12 months. : Spontaneous regression of CIN 1 and 2 occurs frequently within 12 months. Human papillomavirus infection is the major risk factor for persistent CIN. However, HPV testing cannot reliably predict persistence of any lesion.

The Capacity of Mycobacterium tuberculosis To Survive Iron Starvation Might Enable It To Persist in Iron-Deprived Microenvironments of Human Granulomas.

PubMed

Kurthkoti, Krishna; Amin, Hamel; Marakalala, Mohlopheni J; Ghanny, Saleena; Subbian, Selvakumar; Sakatos, Alexandra; Livny, Jonathan; Fortune, Sarah M; Berney, Michael; Rodriguez, G Marcela

2017-08-15

This study was conducted to investigate the role of iron deprivation in the persistence of Mycobacterium tuberculosis We present evidence of iron restriction in human necrotic granulomas and demonstrate that under iron starvation M. tuberculosis persists, refractive to antibiotics and capable of restarting replication when iron is made available. Transcriptomics and metabolomic analyses indicated that the persistence of M. tuberculosis under iron starvation is dependent on strict control of endogenous Fe utilization and is associated with upregulation of pathogenicity and intrinsic antibiotic resistance determinants. M. tuberculosis mutants compromised in their ability to survive Fe starvation were identified. The findings of this study advance the understanding of the physiological settings that may underpin the chronicity of human tuberculosis (TB) and are relevant to the design of effective antitubercular therapies. IMPORTANCE One-third of the world population may harbor persistent M. tuberculosis , causing an asymptomatic infection that is refractory to treatment and can reactivate to become potentially lethal tuberculosis disease. However, little is known about the factors that trigger and maintain M. tuberculosis persistence in infected individuals. Iron is an essential nutrient for M. tuberculosis growth. In this study, we show, first, that in human granulomas the immune defense creates microenvironments in which M. tuberculosis likely experiences drastic Fe deprivation and, second, that Fe-starved M. tuberculosis is capable of long-term persistence without growth. Together, these observations suggest that Fe deprivation in the lung might trigger a state of persistence in M. tuberculosis and promote chronic TB. We also identified vulnerabilities of iron-restricted persistent M. tuberculosis , which can be exploited for the design of new antitubercular therapies. Copyright © 2017 Kurthkoti et al.

Simultaneous quantification of 21 water soluble vitamin circulating forms in human plasma by liquid chromatography-mass spectrometry.

PubMed

Meisser Redeuil, Karine; Longet, Karin; Bénet, Sylvie; Munari, Caroline; Campos-Giménez, Esther

2015-11-27

This manuscript reports a validated analytical approach for the quantification of 21 water soluble vitamins and their main circulating forms in human plasma. Isotope dilution-based sample preparation consisted of protein precipitation using acidic methanol enriched with stable isotope labelled internal standards. Separation was achieved by reversed-phase liquid chromatography and detection performed by tandem mass spectrometry in positive electrospray ionization mode. Instrumental lower limits of detection and quantification reached <0.1-10nM and 0.2-25nM, respectively. Commercially available pooled human plasma was used to build matrix-matched calibration curves ranging 2-500, 5-1250, 20-5000 or 150-37500nM depending on the analyte. The overall performance of the method was considered adequate, with 2.8-20.9% and 5.2-20.0% intra and inter-day precision, respectively and averaged accuracy reaching 91-108%. Recovery experiments were also performed and reached in average 82%. This analytical approach was then applied for the quantification of circulating water soluble vitamins in human plasma single donor samples. The present report provides a sensitive and reliable approach for the quantification of water soluble vitamins and main circulating forms in human plasma. In the future, the application of this analytical approach will give more confidence to provide a comprehensive assessment of water soluble vitamins nutritional status and bioavailability studies in humans. Copyright © 2015 Elsevier B.V. All rights reserved.

Simulated life cycles of persistent anticyclonic anomalies over the North Pacific: Role of synoptic-scale eddies

NASA Technical Reports Server (NTRS)

Higgins, R. W.; Schubert, S. D.

1994-01-01

This study examines the role of synoptic-scale eddies during the development of persistent anticyclonic height anomalies over the central North Pacific in a general circulation model under perpetual January conditions. The General Circulation Model (GCM) replicates the basic characteristics of the evolution of the anomaly patterns found in observations. The life cycle is characterized by the rapid establishment of the major anomaly center and considerably longer maintenance and decay phases, which include the development of downstream anomaly centers. The simulation also shows a realistic evolution of synoptic-scale activity beginning with enhanced activity off the east coast of Asia prior to onset, followed by a northward shift of the Pacific storm track, which lasts throughout the maintenance phase. The initial enhancement of synoptic-scale eddy activity is associated with a large-scale cyclonic anomaly that developes over Siberia several days prior to the onset of the main anticyclonic anomaly over the central North Pacific. The observations, however, show considerable interdecadel variability in the details of the composite onset behavior; it is unclear whether this variability is real or whether it reflects differences in the data assimilation systems. The role of the time mean flow and synoptic-scale eddies in the development of the persistent Pacific anomalies is studied within the context of a kinetic energy budget in which the flow is decomposed into the time-mean, low-frequency (timescales longer than 10 days), and synoptic (timescales less than 6 days) components. The budget, which is carried out for the simulation at 500 mb, shows that the initial growth of the persistent anticyclonic anomalies is associated with barotropic conversions of energy, with approximately equal contributions coming from the mean flow and the synoptic-scale eddies. After onset the barotropic conversion from the mean flow dominates, whereas the decay phase is associated with baroclinic processes within the low-frequency flow.

Systemic right-to-left shunts, ischemic brain lesions, and persistent migraine activity

PubMed Central

Palm-Meinders, Inge H.; Mess, Werner H.; Keunen, Ruud W.; Terwindt, Gisela M.; Launer, Lenore J.; van Buchem, Mark A.; Kruit, Mark C.; Ferrari, Michel D.

2016-01-01

Objective: To assess whether migraine in the general population is associated with increased risk of systemic right-to-left shunts (RLS) and whether RLS are associated with increased prevalence of brain infarcts and persistent recurrence of migraine attacks at older age. Methods: Brain MRI and transcranial Doppler with air contrast in 166 unselected migraineurs (mean age ± SD 56 ± 7.7 years; 70% women; n = 96 migraine with aura) and 69 controls (mean age ± SD 55 ± 7.6 years; 65% women) from the general population. Results: Participants with migraine with aura more frequently had Valsalva-induced RLS (60%), in particular large-sized, compared to controls (42%; odds ratio [OR] 2.1; 95% confidence interval [CI] 1.1–3.9; p = 0.02) and participants with migraine without aura (40%; OR 2.3; 95% CI 1.2–4.3; p = 0.01). They also more frequently had spontaneous RLS (35%) than participants with migraine without aura (17%; OR 2.6; 95% CI 1.3–5.6; p = 0.01) but not compared to controls (26%; OR 1.6; 95% CI 0.8–3.1; p = 0.2). Participants with migraine with aura and spontaneous RLS more frequently had persistent migraine activity (85%) than participants with migraine without spontaneous RLS (63%; OR 3.4; 95% CI 1.2–10.1; p = 0.03). Nine percent of participants with RLS had silent posterior circulation infarcts compared to 3% of participants without RLS (OR 2.8; 95% CI 0.9–9.3; p = 0.08), independent of migraine status. RLS were not associated with white matter lesions. Conclusions: RLS are more prevalent in migraineurs with aura but do not explain the increased prevalence of silent posterior circulation infarcts or white matter lesions in migraineurs. Spontaneous RLS are associated with persistent migraine. PMID:26968513

Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: a Gynecologic Oncology Group study

PubMed Central

Behbakht, Kian; Sill, Michael W.; Darcy, Kathleen M.; Rubin, Stephen C.; Mannel, Robert S.; Waggoner, Steven; Schilder, Russell J.; Cai, Kathy Q.; Godwin, Andrew K.; Alpaugh, R. Katherine

2012-01-01

Purpose Patients with persistent/recurrent epithelial ovarian cancer/primary peritoneal cancer (EOC/PPC) have limited treatment options. AKT and PI3K pathway activation is common in EOC/PPC, resulting in constitutive activation of downstream mTOR. The GOG conducted a phase II evaluation of efficacy and safety for the mTOR inhibitor, temsirolimus in EOC/PPC and explored circulating tumor cells (CTC) and AKT/mTOR/downstream tumor markers. Methods Eligible women with measurable, persistent/recurrent EOC/PPC who had received 1–3 prior regimens were treated with 25 mg weekly IV temsirolimus until progression or intolerable toxicity. Primary endpoints were progression-free survival (PFS) ≥6-months, tumor response, and toxicity. CellSearch® system was used to examine CTC, and AKT/mTOR/downstream markers were evaluated by archival tumor immunohistochemistry. Kendall’s tau-b correlation coefficient (r) and Cox regression modeling were used to explore marker associations with baseline characteristics and outcome. Results Sixty patients were enrolled in a two-stage sequential design. Of 54 eligible and evaluable patients, 24.1% (90%CI 14.9%–38.6%) had PFS ≥6 months (median 3.1 months), 9.3% (90%CI 3.7%–23.4%) experienced a partial response. Grade 3/4 adverse events included metabolic(8), gastrointestinal(8), pain(6), constitutional(5) and pulmonary(4). Suggested associations were between cyclin D1 and PFS ≥6 months, PFS or survival; positive CTC pre-treatment and lack of response; and high CTC expression of M30 and PFS ≥6 months/longer PFS. Conclusions Temsirolimus appears to have modest activity in persistent/recurrent EOC/PPC; however, PFS is just below that required to warrant inclusion in phase III studies in unselected patients. Cyclin D1 as a selection marker and CTC measures merit further study. PMID:21752435

Distribution, persistence and interchange of Epstein-Barr virus strains among PBMC, plasma and saliva of primary infection subjects.

PubMed

Kwok, Hin; Chan, Koon Wing; Chan, Kwok Hung; Chiang, Alan Kwok Shing

2015-01-01

Our study aimed at investigating the distribution, persistence and interchange of viral strains among peripheral blood mononuclear cells (PBMC), plasma and saliva of primary Epstein-Barr virus (EBV) infection subjects. Twelve infectious mononucleosis (IM) patients and eight asymptomatic individuals (AS) with primary EBV infection were followed longitudinally at several time points for one year from the time of diagnosis, when blood and saliva samples were collected and separated into PBMC, plasma and saliva, representing circulating B cell, plasma and epithelial cell compartments, respectively. To survey the viral strains, genotyping assays for the natural polymorphisms in two latent EBV genes, EBNA2 and LMP1, were performed and consisted of real-time PCR on EBNA2 to distinguish type 1 and 2 viruses, fluorescent-based 30-bp typing assay on LMP1 to distinguish deletion and wild type LMP1, and fluorescent-based heteroduplex tracking assays on both EBNA2 and LMP1 to distinguish defined polymorphic variants. No discernible differences were observed between IM patients and AS. Multiple viral strains were acquired early at the start of infection. Stable persistence of dominant EBV strains in the same tissue compartment was observed throughout the longitudinal samples. LMP1-defined strains, China 1, China 2 and Mediterranean+, were the most common strains observed. EBNA2-defined groups 1 and 3e predominated the PBMC and saliva compartments. Concordance of EBNA2 and LMP1 strains between PBMC and saliva suggested ready interchange of viruses between circulating B cell and epithelial cell pools, whilst discordance of viral strains observed between plasma and PBMC/saliva indicated presence of viral pools in other undetermined tissue compartments. Taken together, the results indicated that the distribution, persistence and interchange of viral strains among the tissue compartments are more complex than those proposed by the current model of EBV life cycle.

Systemic right-to-left shunts, ischemic brain lesions, and persistent migraine activity.

PubMed

Koppen, Hille; Palm-Meinders, Inge H; Mess, Werner H; Keunen, Ruud W; Terwindt, Gisela M; Launer, Lenore J; van Buchem, Mark A; Kruit, Mark C; Ferrari, Michel D

2016-05-03

To assess whether migraine in the general population is associated with increased risk of systemic right-to-left shunts (RLS) and whether RLS are associated with increased prevalence of brain infarcts and persistent recurrence of migraine attacks at older age. Brain MRI and transcranial Doppler with air contrast in 166 unselected migraineurs (mean age ± SD 56 ± 7.7 years; 70% women; n = 96 migraine with aura) and 69 controls (mean age ± SD 55 ± 7.6 years; 65% women) from the general population. Participants with migraine with aura more frequently had Valsalva-induced RLS (60%), in particular large-sized, compared to controls (42%; odds ratio [OR] 2.1; 95% confidence interval [CI] 1.1-3.9; p = 0.02) and participants with migraine without aura (40%; OR 2.3; 95% CI 1.2-4.3; p = 0.01). They also more frequently had spontaneous RLS (35%) than participants with migraine without aura (17%; OR 2.6; 95% CI 1.3-5.6; p = 0.01) but not compared to controls (26%; OR 1.6; 95% CI 0.8-3.1; p = 0.2). Participants with migraine with aura and spontaneous RLS more frequently had persistent migraine activity (85%) than participants with migraine without spontaneous RLS (63%; OR 3.4; 95% CI 1.2-10.1; p = 0.03). Nine percent of participants with RLS had silent posterior circulation infarcts compared to 3% of participants without RLS (OR 2.8; 95% CI 0.9-9.3; p = 0.08), independent of migraine status. RLS were not associated with white matter lesions. RLS are more prevalent in migraineurs with aura but do not explain the increased prevalence of silent posterior circulation infarcts or white matter lesions in migraineurs. Spontaneous RLS are associated with persistent migraine. © 2016 American Academy of Neurology.

Distribution, Persistence and Interchange of Epstein-Barr Virus Strains among PBMC, Plasma and Saliva of Primary Infection Subjects

PubMed Central

Kwok, Hin; Chan, Koon Wing; Chan, Kwok Hung; Chiang, Alan Kwok Shing

2015-01-01

Our study aimed at investigating the distribution, persistence and interchange of viral strains among peripheral blood mononuclear cells (PBMC), plasma and saliva of primary Epstein-Barr virus (EBV) infection subjects. Twelve infectious mononucleosis (IM) patients and eight asymptomatic individuals (AS) with primary EBV infection were followed longitudinally at several time points for one year from the time of diagnosis, when blood and saliva samples were collected and separated into PBMC, plasma and saliva, representing circulating B cell, plasma and epithelial cell compartments, respectively. To survey the viral strains, genotyping assays for the natural polymorphisms in two latent EBV genes, EBNA2 and LMP1, were performed and consisted of real-time PCR on EBNA2 to distinguish type 1 and 2 viruses, fluorescent-based 30-bp typing assay on LMP1 to distinguish deletion and wild type LMP1, and fluorescent-based heteroduplex tracking assays on both EBNA2 and LMP1 to distinguish defined polymorphic variants. No discernible differences were observed between IM patients and AS. Multiple viral strains were acquired early at the start of infection. Stable persistence of dominant EBV strains in the same tissue compartment was observed throughout the longitudinal samples. LMP1-defined strains, China 1, China 2 and Mediterranean+, were the most common strains observed. EBNA2-defined groups 1 and 3e predominated the PBMC and saliva compartments. Concordance of EBNA2 and LMP1 strains between PBMC and saliva suggested ready interchange of viruses between circulating B cell and epithelial cell pools, whilst discordance of viral strains observed between plasma and PBMC/saliva indicated presence of viral pools in other undetermined tissue compartments. Taken together, the results indicated that the distribution, persistence and interchange of viral strains among the tissue compartments are more complex than those proposed by the current model of EBV life cycle. PMID:25807555

Numerical analysis of seawater circulation in carbonate platforms: II. The dynamic interaction between geothermal and brine reflux circulation

USGS Publications Warehouse

Jones, G.D.; Whitaker, F.F.; Smart, P.L.; Sanford, W.E.

2004-01-01

Density-driven seawater circulation may occur in carbonate platforms due to geothermal heating and / or reflux of water of elevated salinity. In geothermal circulation lateral contrasts in temperature between seawater and platform groundwaters warmed by the geothermal heat flux result in upward convective flow, with colder seawater drawn into the platform at depth. With reflux circulation, platform-top waters concentrated by evaporation flow downward, displacing less dense underlying groundwaters. We have used a variable density groundwater flow model to examine the pattern, magnitude and interaction of these two different circulation mechanisms, for mesosaline platform-top waters (50???) and brines concentrated up to saturation with respect to gypsum (150???) and halite (246???). Geothermal circulation, most active around the platform margin, becomes restricted and eventually shut-off by reflux of brines from the platform interior towards the margin. The persistence of geothermal circulation is dependent on the rate of brine reflux, which is proportional to the concentration of platform-top brines and also critically dependent on the magnitude and distribution of permeability. Low permeability evaporites can severely restrict reflux whereas high permeability units in hydraulic continuity enhance brine transport. Reduction in permeability with depth and anisotropy of permeability (kv < < kh) focuses flow laterally in the shallow subsurface (<1 km), resulting in a horizontally elongated brine plume. Aquifer porosity and dispersivity are relatively minor controls on reflux. Platform brines can entrain surficial seawater when brine generating conditions cease but the platform-top remains submerged, a variant of reflux we term "latent reflux". Brines concentrated up to gypsum saturation have relatively long residence times of at least 100 times the duration of the reflux event. They thus represent a long-term control on post-reflux groundwater circulation, and consequently on the rates and spatial patterns of shallow burial diagenesis, such as dolomitization.

PASSIVE CAVITATION DETECTION DURING PULSED HIFU EXPOSURES OF EX VIVO TISSUES AND IN VIVO MOUSE PANCREATIC TUMORS

PubMed Central

Li, Tong; Chen, Hong; Khokhlova, Tatiana; Wang, Yak-Nam; Kreider, Wayne; He, Xuemei; Hwang, Joo Ha

2014-01-01

Pulsed high-intensity focused ultrasound (pHIFU) has been demonstrated to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rarefactional focal pressures (1–12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms, pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KPC mice and closely recapitulate human disease in their morphology. The cavitation threshold, defined at 50 % cavitation probability, was found to vary broadly among the investigated tissues (within 2.5–10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but ex vivo it decreased rapidly and stopped over the first few pulses. Cavitation activity depended on the interplay between the destruction and circulation of cavitation nuclei, which are not only used up by HIFU treatment but also replenished or carried away by circulation in vivo. These findings are important for treatment planning and optimization in pHIFU-induced drug delivery, in particular for pancreatic tumors. PMID:24613635

Stress hormone levels in a freshwater turtle from sites differing in human activity.

PubMed

Polich, Rebecca L

2016-01-01

Glucocorticoids, such as corticosterone (CORT), commonly serve as a measure of stress levels in vertebrate populations. These hormones have been implicated in regulation of feeding behaviour, locomotor activity, body mass, lipid metabolism and other crucial behaviours and physiological processes. Thus, understanding how glucocorticoids fluctuate seasonally and in response to specific stressors can yield insight into organismal health and the overall health of populations. I compared circulating CORT concentrations between two similar populations of painted turtle, Chrysemys picta, which differed primarily in the level of exposure to human recreational activities. I measured basal CORT concentrations as well as the CORT stress response and did not find any substantive difference between the two populations. This similarity may indicate that painted turtles are not stressed by the presence of humans during the nesting season. The results of this study contribute to our understanding of CORT concentrations in freshwater reptiles, a group that is historically under-represented in studies of circulating hormone concentrations; specifically, studies that seek to use circulating concentrations of stress hormones, such as CORT, as a measure of the effect of human activities on wild populations. They also give insight into how these species as a whole may respond to human recreational activities during crucial life-history stages, such as the nesting season. Although there was no discernable difference between circulating CORT concentrations between the urban and rural populations studied, I did find a significant difference in circulating CORT concentrations between male and female C. picta. This important finding provides better understanding of the sex differences between male and female painted turtles and adds to our understanding of this species and other species of freshwater turtle.

A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels.

PubMed

Khetarpal, Sumeet A; Zeng, Xuemei; Millar, John S; Vitali, Cecilia; Somasundara, Amritha Varshini Hanasoge; Zanoni, Paolo; Landro, James A; Barucci, Nicole; Zavadoski, William J; Sun, Zhiyuan; de Haard, Hans; Toth, Ildikó V; Peloso, Gina M; Natarajan, Pradeep; Cuchel, Marina; Lund-Katz, Sissel; Phillips, Michael C; Tall, Alan R; Kathiresan, Sekar; DaSilva-Jardine, Paul; Yates, Nathan A; Rader, Daniel J

2017-09-01

Recent large-scale genetic sequencing efforts have identified rare coding variants in genes in the triglyceride-rich lipoprotein (TRL) clearance pathway that are protective against coronary heart disease (CHD), independently of LDL cholesterol (LDL-C) levels. Insight into the mechanisms of protection of these variants may facilitate the development of new therapies for lowering TRL levels. The gene APOC3 encodes apoC-III, a critical inhibitor of triglyceride (TG) lipolysis and remnant TRL clearance. Here we report a detailed interrogation of the mechanism of TRL lowering by the APOC3 Ala43Thr (A43T) variant, the only missense (rather than protein-truncating) variant in APOC3 reported to be TG lowering and protective against CHD. We found that both human APOC3 A43T heterozygotes and mice expressing human APOC3 A43T display markedly reduced circulating apoC-III levels. In mice, this reduction is due to impaired binding of A43T apoC-III to lipoproteins and accelerated renal catabolism of free apoC-III. Moreover, the reduced content of apoC-III in TRLs resulted in accelerated clearance of circulating TRLs. On the basis of this protective mechanism, we developed a monoclonal antibody targeting lipoprotein-bound human apoC-III that promotes circulating apoC-III clearance in mice expressing human APOC3 and enhances TRL catabolism in vivo. These data reveal the molecular mechanism by which a missense variant in APOC3 causes reduced circulating TG levels and, hence, protects from CHD. This protective mechanism has the potential to be exploited as a new therapeutic approach to reduce apoC-III levels and circulating TRL burden.

A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels

PubMed Central

Khetarpal, Sumeet A; Zeng, Xuemei; Millar, John S; Vitali, Cecilia; Somasundara, Amritha Varshini Hanasoge; Zanoni, Paolo; Landro, James A; Barucci, Nicole; Zavadoski, William J; Sun, Zhiyuan; de Haard, Hans; Toth, Ildikó V; Peloso, Gina M; Natarajan, Pradeep; Cuchel, Marina; Lund-Katz, Sissel; Phillips, Michael C; Tall, Alan R; Kathiresan, Sekar; DaSilva-Jardine, Paul; Yates, Nathan A; Rader, Daniel J

2017-01-01

Recent large-scale genetic sequencing efforts have identified rare coding variants in genes in the triglyceride-rich lipoprotein (TRL) clearance pathway that are protective against coronary heart disease (CHD), independently of LDL cholesterol (LDL-C) levels1. Insight into the mechanisms of protection of these variants may facilitate the development of new therapies for lowering TRL levels. The gene APOC3 encodes apoC-III, a critical inhibitor of triglyceride (TG) lipolysis and remnant TRL clearance2. Here we report a detailed interrogation of the mechanism of TRL lowering by the APOC3 Ala43Thr (A43T) variant, the only missense (rather than protein-truncating) variant in APOC3 reported to be TG lowering and protective against CHD3–5. We found that both human APOC3 A43T heterozygotes and mice expressing human APOC3 A43T display markedly reduced circulating apoC-III levels. In mice, this reduction is due to impaired binding of A43T apoC-III to lipoproteins and accelerated renal catabolism of free apoC-III. Moreover, the reduced content of apoC-III in TRLs resulted in accelerated clearance of circulating TRLs. On the basis of this protective mechanism, we developed a monoclonal antibody targeting lipoprotein-bound human apoC-III that promotes circulating apoC-III clearance in mice expressing human APOC3 and enhances TRL catabolism in vivo. These data reveal the molecular mechanism by which a missense variant in APOC3 causes reduced circulating TG levels and, hence, protects from CHD. This protective mechanism has the potential to be exploited as a new therapeutic approach to reduce apoC-III levels and circulating TRL burden. PMID:28825717

Development of a hydraulic model of the human systemic circulation

NASA Technical Reports Server (NTRS)

Sharp, M. K.; Dharmalingham, R. K.

1999-01-01

Physical and numeric models of the human circulation are constructed for a number of objectives, including studies and training in physiologic control, interpretation of clinical observations, and testing of prosthetic cardiovascular devices. For many of these purposes it is important to quantitatively validate the dynamic response of the models in terms of the input impedance (Z = oscillatory pressure/oscillatory flow). To address this need, the authors developed an improved physical model. Using a computer study, the authors first identified the configuration of lumped parameter elements in a model of the systemic circulation; the result was a good match with human aortic input impedance with a minimum number of elements. Design, construction, and testing of a hydraulic model analogous to the computer model followed. Numeric results showed that a three element model with two resistors and one compliance produced reasonable matching without undue complication. The subsequent analogous hydraulic model included adjustable resistors incorporating a sliding plate to vary the flow area through a porous material and an adjustable compliance consisting of a variable-volume air chamber. The response of the hydraulic model compared favorably with other circulation models.

Sequence-Dependent Persistence Length of Long DNA

NASA Astrophysics Data System (ADS)

Chuang, Hui-Min; Reifenberger, Jeffrey G.; Cao, Han; Dorfman, Kevin D.

2017-12-01

Using a high-throughput genome-mapping approach, we obtained circa 50 million measurements of the extension of internal human DNA segments in a 41 nm ×41 nm nanochannel. The underlying DNA sequences, obtained by mapping to the reference human genome, are 2.5-393 kilobase pairs long and contain percent GC contents between 32.5% and 60%. Using Odijk's theory for a channel-confined wormlike chain, these data reveal that the DNA persistence length increases by almost 20% as the percent GC content increases. The increased persistence length is rationalized by a model, containing no adjustable parameters, that treats the DNA as a statistical terpolymer with a sequence-dependent intrinsic persistence length and a sequence-independent electrostatic persistence length.

Evolution of lactase persistence: an example of human niche construction

PubMed Central

Gerbault, Pascale; Liebert, Anke; Itan, Yuval; Powell, Adam; Currat, Mathias; Burger, Joachim; Swallow, Dallas M.; Thomas, Mark G.

2011-01-01

Niche construction is the process by which organisms construct important components of their local environment in ways that introduce novel selection pressures. Lactase persistence is one of the clearest examples of niche construction in humans. Lactase is the enzyme responsible for the digestion of the milk sugar lactose and its production decreases after the weaning phase in most mammals, including most humans. Some humans, however, continue to produce lactase throughout adulthood, a trait known as lactase persistence. In European populations, a single mutation (−13910*T) explains the distribution of the phenotype, whereas several mutations are associated with it in Africa and the Middle East. Current estimates for the age of lactase persistence-associated alleles bracket those for the origins of animal domestication and the culturally transmitted practice of dairying. We report new data on the distribution of −13910*T and summarize genetic studies on the diversity of lactase persistence worldwide. We review relevant archaeological data and describe three simulation studies that have shed light on the evolution of this trait in Europe. These studies illustrate how genetic and archaeological information can be integrated to bring new insights to the origins and spread of lactase persistence. Finally, we discuss possible improvements to these models. PMID:21320900

HUMAN HEALTH IMPACTS OF EXPOSURE TO POPS

EPA Science Inventory

The Stockholm Convention on persistent organic pollutants (POPs) was adopted in 2001 to protect human health and the environment from chemicals that are highly toxic, persistent, bioaccumulative and undergo long range transport. These POPs include 9 pesticides, polychlorinated d...

Geothermal heating enhances atmospheric asymmetries on synchronously rotating planets

NASA Astrophysics Data System (ADS)

Haqq-Misra, Jacob; Kopparapu, Ravi Kumar

2015-01-01

Earth-like planets within the liquid water habitable zone of M-type stars may evolve into synchronous rotators. On these planets, the substellar hemisphere experiences perpetual daylight while the opposing antistellar hemisphere experiences perpetual darkness. Because the night-side hemisphere has no direct source of energy, the air over this side of the planet is prone to freeze out and deposit on the surface, which could result in atmospheric collapse. However, general circulation models (GCMs) have shown that atmospheric dynamics can counteract this problem and provide sufficient energy transport to the antistellar side. Here, we use an idealized GCM to consider the impact of geothermal heating on the habitability of synchronously rotating planets. Geothermal heating may be expected due to tidal interactions with the host star, and the effects of geothermal heating provide additional habitable surface area and may help to induce melting of ice on the antistellar hemisphere. We also explore the persistence of atmospheric asymmetries between the Northern and Southern hemispheres, and we find that the direction of the meridional circulation (for rapidly rotating planets) or the direction of zonal wind (for slowly rotating planets) reverses on either side of the substellar point. We show that the zonal circulation approaches a theoretical state similar to a Walker circulation only for slowly rotating planets, while rapidly rotating planets show a zonal circulation with the opposite direction. We find that a cross-polar circulation is present in all cases and provides an additional mechanism of mass and energy transport from the substellar to antistellar point. Characterization of the atmospheres of synchronously rotating planets should include consideration of hemispheric differences in meridional circulation and examination of transport due to cross-polar flow.

Reconstructing Deep Ocean Circulation in the North Atlantic from Bermuda Rise, and Beyond

NASA Astrophysics Data System (ADS)

McManus, J. F.

2016-12-01

The large-scale subsurface circulation of the ocean is an important component of the Earth's climate system, and contributes to the global and regional transport of heat and mass. Assessing how this system has changed in the past is thus a priority for understanding natural climate variability. A long-coring campaign on Bermuda Rise has provided additional abundant high-quality sediments from this site of rapid accumulation in the deep western basin, situated beneath the subtropical gyre of the North Atlantic Ocean. These sediments allow the high-resolution reconstruction of deepwater chemistry and export from this key location throughout the last 150,000 years, covering the entire last glacial cycle in a continuous section of 35 meters in core KNR191-CDH19. The suite of proxy indicators analyzed includes uranium-series disequilibria, neodymium isotopes, and benthic stable isotopes. Combined with multiple previous studies of nearby cores on Bermuda Rise, the published and new proxy data from CDH19 confirm the variability of the deep circulation in the Atlantic Ocean in association with past climate changes. The multiple indicators, along with complementary data from other locations, display coherent evidence for contrasts between deep circulation during glacial and interglacial intervals, with persistent strong, deep ventilation only within the peak interglacial of marine isotope stage 5e (MIS 5e) and the Holocene. In contrast, repeated, dramatic variability in deep ocean circulation accompanied the millennial climate changes of the last glaciation and deglaciation. The largest magnitude circulation shifts occurred at the transitions into stadials associated with the Hudson strait iceberg discharges and between them and the ensuing northern interstadial warmings, significantly exceeding that of the overall glacial-interglacial difference, highlighting the potential oceanographic and climatic importance of short-term perturbations to the deep ocean circulation.

Rabies Virus Exposure of Brazilian Free-ranging Wildlife from Municipalities without Clinical Cases in Humans or in Terrestrial Wildlife.

PubMed

Marcelo Azevedo de Paula Antunes, João; de Castro Demoner, Larissa; Morosini de Andrade Cruvinel, Tatiana; Paula Kataoka, Ana; Fátima Alves Martorelli, Luzia; Puglia Machado, Gustavo; Megid, Jane

2017-07-01

Rabies is a zoonosis that causes thousands of animal and human deaths worldwide. Serological studies provide information concerning rabies virus circulation among animals and humans. We evaluated the circulation of the rabies virus in wildlife in nine municipalities of São Paulo State, Brazil. We took blood samples from 27 terrestrial animals of nine different mammalian species in locations without cases of rabies in human and wild terrestrial mammals. Sera were tested with the use of the rapid fluorescent focus inhibition test (RFFIT) for the detection of rabies virus-neutralizing antibodies (RVNA). The RFFIT was positive in 100% of the samples, with many (81.48%) showing protective titer levels (>0.5 IU/mL) with other samples (18.52%) showing titers representing exposure (<0.5 IU/mL). We report RVNA in novel species (e.g., Alouatta caraya and Tapyrus terrestris). Wild animals were exposed to rabies virus in municipalities without a history of human rabies cases, which demonstrated a need for research to understand the role of these animals in the circulation and transmission of the disease.

Sources and functions of extracellular small RNAs in human circulation

PubMed Central

Fritz, Joëlle V.; Heintz-Buschart, Anna; Ghosal, Anubrata; Wampach, Linda; Etheridge, Alton; Galas, David; Wilmes, Paul

2017-01-01

Various biotypes of endogenous small RNAs (sRNAs) have been detected in human circulation including microRNAs, tRNA, rRNA and yRNA fragments. These extracellular sRNAs (ex-sRNAs) are packaged and secreted by many different cell types. Ex-sRNAs exhibit differences in abundance in several disease contexts and have therefore been proposed as well-suited biomarkers. Furthermore, exosome-borne ex-sRNAs have been reported to elicit physiological responses in receiving cells. Albeit controversial, exogenous ex-sRNAs derived from plants and microorganisms have also been described in human blood. Essential questions which remain to be conclusively addressed in the field concern the (i) presence and mechanistic sources of exogenous ex-sRNA in human bodily fluids, (ii) detection and measurement of ex-sRNA in human circulation, (iii) selectivity of ex-sRNA export and import, (iv) sensitivity and specificity of ex-sRNA delivery to cellular targets, and (v) cell-, tissue-, organ- and organism-wide impacts of ex-sRNAs. We will survey the present state of knowledge of most of these questions in this review. PMID:27215587

Numerous uncharacterized and highly divergent microbes which colonize humans are revealed by circulating cell-free DNA

PubMed Central

Camunas-Soler, Joan; Kertesz, Michael; De Vlaminck, Iwijn; Koh, Winston; Pan, Wenying; Martin, Lance; Neff, Norma F.; Okamoto, Jennifer; Wong, Ronald J.; Kharbanda, Sandhya; El-Sayed, Yasser; Blumenfeld, Yair; Stevenson, David K.; Shaw, Gary M.; Wolfe, Nathan D.; Quake, Stephen R.

2017-01-01

Blood circulates throughout the human body and contains molecules drawn from virtually every tissue, including the microbes and viruses which colonize the body. Through massive shotgun sequencing of circulating cell-free DNA from the blood, we identified hundreds of new bacteria and viruses which represent previously unidentified members of the human microbiome. Analyzing cumulative sequence data from 1,351 blood samples collected from 188 patients enabled us to assemble 7,190 contiguous regions (contigs) larger than 1 kbp, of which 3,761 are novel with little or no sequence homology in any existing databases. The vast majority of these novel contigs possess coding sequences, and we have validated their existence both by finding their presence in independent experiments and by performing direct PCR amplification. When their nearest neighbors are located in the tree of life, many of the organisms represent entirely novel taxa, showing that microbial diversity within the human body is substantially broader than previously appreciated. PMID:28830999

Support for viral persistence in bats from age-specific serology and models of maternal immunity.

PubMed

Peel, Alison J; Baker, Kate S; Hayman, David T S; Broder, Christopher C; Cunningham, Andrew A; Fooks, Anthony R; Garnier, Romain; Wood, James L N; Restif, Olivier

2018-03-01

Spatiotemporally-localised prediction of virus emergence from wildlife requires focused studies on the ecology and immunology of reservoir hosts in their native habitat. Reliable predictions from mathematical models remain difficult in most systems due to a dearth of appropriate empirical data. Our goal was to study the circulation and immune dynamics of zoonotic viruses in bat populations and investigate the effects of maternally-derived and acquired immunity on viral persistence. Using rare age-specific serological data from wild-caught Eidolon helvum fruit bats as a case study, we estimated viral transmission parameters for a stochastic infection model. We estimated mean durations of around 6 months for maternally-derived immunity to Lagos bat virus and African henipavirus, whereas acquired immunity was long-lasting (Lagos bat virus: mean 12 years, henipavirus: mean 4 years). In the presence of a seasonal birth pulse, the effect of maternally-derived immunity on virus persistence within modelled bat populations was highly dependent on transmission characteristics. To explain previous reports of viral persistence within small natural and captive E. helvum populations, we hypothesise that some bats must experience prolonged infectious periods or within-host latency. By further elucidating plausible mechanisms of virus persistence in bat populations, we contribute to guidance of future field studies.

Mechanisms of HIV persistence in HIV reservoirs.

PubMed

Mzingwane, Mayibongwe L; Tiemessen, Caroline T

2017-03-01

The establishment and maintenance of HIV reservoirs that lead to persistent viremia in patients on antiretroviral drugs remains the greatest challenge of the highly active antiretroviral therapy era. Cellular reservoirs include resting memory CD4+ T lymphocytes, implicated as the major HIV reservoir, having a half-life of approximately 44 months while this is less than 6 hours for HIV in plasma. In some individuals, persistent viremia consists of invariant HIV clones not detected in circulating resting CD4+ T lymphocytes suggesting other possible sources of residual viremia. Some anatomical reservoirs that may harbor such cells include the brain and the central nervous system, the gastrointestinal tract and the gut-associated lymphoid tissue and other lymphoid organs, and the genital tract. The presence of immune cells and other HIV susceptible cells, occurring in differing compositions in anatomical reservoirs, coupled with variable and poor drug penetration that results in suboptimal drug concentrations in some sites, are all likely factors that fuel the continued low-level replication and persistent viremia during treatment. Latently, HIV-infected CD4+ T cells harboring replication-competent virus, HIV cell-to-cell spread, and HIV-infected T cell homeostatic proliferation due to chronic immune activation represent further drivers of this persistent HIV viremia during highly active antiretroviral therapy. Copyright © 2017 John Wiley & Sons, Ltd.

Avian Influenza Virus Infection of Immortalized Human Respiratory Epithelial Cells Depends upon a Delicate Balance between Hemagglutinin Acid Stability and Endosomal pH.

PubMed

Daidoji, Tomo; Watanabe, Yohei; Ibrahim, Madiha S; Yasugi, Mayo; Maruyama, Hisataka; Masuda, Taisuke; Arai, Fumihito; Ohba, Tomoyuki; Honda, Ayae; Ikuta, Kazuyoshi; Nakaya, Takaaki

2015-04-24

The highly pathogenic avian influenza (AI) virus, H5N1, is a serious threat to public health worldwide. Both the currently circulating H5N1 and previously circulating AI viruses recognize avian-type receptors; however, only the H5N1 is highly infectious and virulent in humans. The mechanism(s) underlying this difference in infectivity remains unclear. The aim of this study was to clarify the mechanisms responsible for the difference in infectivity between the current and previously circulating strains. Primary human small airway epithelial cells (SAECs) were transformed with the SV40 large T-antigen to establish a series of clones (SAEC-Ts). These clones were then used to test the infectivity of AI strains. Human SAEC-Ts could be broadly categorized into two different types based on their susceptibility (high or low) to the viruses. SAEC-T clones were poorly susceptible to previously circulating AI but were completely susceptible to the currently circulating H5N1. The hemagglutinin (HA) of the current H5N1 virus showed greater membrane fusion activity at higher pH levels than that of previous AI viruses, resulting in broader cell tropism. Moreover, the endosomal pH was lower in high susceptibility SAEC-T clones than that in low susceptibility SAEC-T clones. Taken together, the results of this study suggest that the infectivity of AI viruses, including H5N1, depends upon a delicate balance between the acid sensitivity of the viral HA and the pH within the endosomes of the target cell. Thus, one of the mechanisms underlying H5N1 pathogenesis in humans relies on its ability to fuse efficiently with the endosomes in human airway epithelial cells. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Indian summer monsoon rainfall variability in response to differences in the decay phase of El Niño

NASA Astrophysics Data System (ADS)

Chowdary, Jasti S.; Harsha, H. S.; Gnanaseelan, C.; Srinivas, G.; Parekh, Anant; Pillai, Prasanth; Naidu, C. V.

2017-04-01

In general the Indian summer monsoon (ISM) rainfall is near normal or excess during the El Niño decay phase. Nevertheless the impact of large variations in decaying El Niño on the ISM rainfall and circulation is not systematically examined. Based on the timing of El Niño decay with respect to boreal summer season, El Niño decay phases are classified into three types in this study using 142 years of sea surface temperature (SST) data, which are as follows: (1) early-decay (ED; decay during spring), (2) mid-summer decay (MD; decay by mid-summer) and (3) no-decay (ND; no decay in summer). It is observed that ISM rainfall is above normal/excess during ED years, normal during MD years and below normal/deficit in ND years, suggesting that the differences in El Niño decay phase display profound impact on the ISM rainfall. Tropical Indian Ocean (TIO) SST warming, induced by El Niño, decays rapidly before the second half of the monsoon season (August and September) in ED years, but persists up to the end of the season in MD years, whereas TIO warming maintained up to winter in ND case. Analysis reveals the existence of strong sub-seasonal ISM rainfall variations in the summer following El Niño years. During ED years, strong negative SST anomalies develop over the equatorial central-eastern Pacific by June and are apparent throughout the summer season accompanied by anomalous moisture divergence and high sea level pressure (SLP). The associated moisture convergence and low SLP over ISM region favour excess rainfall (mainly from July onwards). This circulation and rainfall anomalies are highly influenced by warm TIO SST and Pacific La Niña conditions in ED years. Convergence of southwesterlies from Arabian Sea and northeasterlies from Bay of Bengal leads to positive rainfall over most part of the Indian subcontinent from August onwards in MD years. ND years are characterized by negative rainfall anomaly spatial pattern and weaker circulation over India throughout the summer season, which are mainly due to persisting El Niño related warm SST anomalies over the Pacific. Atmospheric general circulation model simulation supports our hypothesis that El Niño decay variations modulate ISM rainfall and circulation.

Omalizumab therapy is associated with reduced circulating basophil populations in asthmatic children

PubMed Central

Hill, D.A.; Siracusa, M.; Ruymann, K.; Wojno, E.D. Tait; Artis, D.; Spergel, J.M.

2014-01-01

Basophils have been implicated in promoting the early development of TH2 cell responses in some murine models of TH2 cytokine-associated inflammation. However, the specific role of basophils in allergic asthma remains an active area of research. Recent studies in animal models and human subjects suggest that IgE may regulate the homeostasis of human basophil populations. Here, we examine basophil populations in children with severe asthma before and during therapy with the IgE directed monoclonal antibody omalizumab. Omalizumab therapy was associated with a significant reduction in circulating basophil numbers, a finding that was concurrent with improved clinical outcomes. The observation that circulating basophils are reduced following omalizumab therapy supports a mechanistic link between IgE levels and circulating basophil populations and may provide new insights into one mechanism by which omalizumab improves asthma symptoms. PMID:24611974

Relationships between serum-induced AhR bioactivity or mitochondrial inhibition and circulating polychlorinated biphenyls (PCBs).

PubMed

Park, Wook Ha; Kang, Sora; Lee, Hong Kyu; Salihovic, Samira; Bavel, Bert van; Lind, P Monica; Pak, Youngmi Kim; Lind, Lars

2017-08-24

Metabolic syndrome and mitochondrial dysfunction have been linked to elevated serum levels of persistent organic pollutants (POPs). However, it is not clear which specific POPs contribute to aryl hydrocarbon receptor (AhR)-dependent bioactivity or inhibit mitochondrial function in human subjects. Here, we measured the cumulative bioactivity of AhR ligand mixture (AhR bioactivity) and the effects on mitochondrial function (ATP concentration) in recombinant Hepa1c1c7 cells incubated with raw serum samples obtained from 911 elderly subjects in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. Plasma concentrations of 30 POPs and plastic chemicals have previously been determined in the same PIVUS subjects. Linear regression analysis demonstrated that total toxic equivalence (TEQ) values and polychlorinated biphenyls (PCBs) were significantly correlated with AhR bioactivity (positively) and ATP concentration (negatively). Serum AhR bioactivities were positively associated with some PCBs, regardless of their dioxin-like properties, but only dioxin-like PCBs stimulated AhR bioactivity. By contrast, PCBs mediated a reduction in ATP content independently of their dioxin-like properties. This study suggests that AhR bioactivity and ATP concentrations in serum-treated cells may be valuable surrogate biomarkers of POP exposure and could be useful for the estimation of the effects of POPs on human health.

Epigenetic Changes in Diabetes and Cardiovascular Risk

PubMed Central

Keating, Samuel T; Plutzky, Jorge; El-Osta, Assam

2016-01-01

Cardiovascular complications remain the leading causes of morbidity and premature mortality in patients with diabetes. Studies in humans and preclinical models demonstrate lasting gene expression changes in the vasculopathies initiated by previous exposure to high glucose concentrations and the associated overproduction of reactive oxygen species. The molecular signatures of chromatin architectures that sensitize the genome to these and other cardiometabolic risk factors of the diabetic milieu are increasingly implicated in the biologic memory underlying cardiovascular complications and now widely considered as promising therapeutic targets. Atherosclerosis is a complex heterocellular disease where the contributing cell types possess distinct epigenomes shaping diverse gene expression. While the extent that pathological chromatin changes can be manipulated in human cardiovascular disease remains to be established, the clinical applicability of epigenetic interventions will be greatly advanced by a deeper understanding of the cell type-specific roles played by writers, erasers, and readers of chromatin modifications in the diabetic vasculature. This review details a current perspective of epigenetic mechanisms of macrovascular disease in diabetes, and highlights recent key descriptions of chromatinized changes associated with persistent gene expression in endothelial, smooth muscle, and circulating immune cells relevant to atherosclerosis. Furthermore we discuss the challenges associated with pharmacological targeting of epigenetic networks to correct abnormal or deregulated gene expression as a strategy to alleviate the clinical burden of diabetic cardiovascular disease. PMID:27230637

A murine model of infection with Rickettsia prowazekii: implications for pathogenesis of epidemic typhus.

PubMed

Bechah, Yassina; Capo, Christian; Grau, Georges E; Raoult, Didier; Mege, Jean-Louis

2007-06-01

Epidemic typhus remains a major disease threat, furthermore, its etiologic agent, Rickettsia prowazekii, is classified as a bioterrorism agent. We describe here a murine model of epidemic typhus that reproduced some features of the human disease. When BALB/c mice were inoculated intravenously with R. prowazekii (Breinl strain), they survived but did not clear R. prowazekii infection. Immunohistological analysis of tissues and quantitative PCR showed that R. prowazekii was present in blood, liver, lungs and brain 1 day after infection and persisted for at least 9 days. Importantly, infected mice developed interstitial pneumonia, with consolidation of the alveoli, hemorrhages in lungs, multifocal granulomas in liver, and hemorrhages in brain, as seen in humans. Circulating antibodies directed against R. prowazekii were detected at day 4 post-infection and steadily increased for up to 21 days, demonstrating that R. prowazekii lesions were independent of humoral immune response. R. prowazekii-induced lesions were associated with inflammatory response, as demonstrated by elevated levels of inflammatory cytokines including interferon-gamma, tumor necrosis factor and the CC chemokine RANTES in the lesions. We concluded that the BALB/c mouse strain provides a useful model for studying the pathogenic mechanisms of epidemic typhus and its control by the immune system.

The challenging use and interpretation of circulating biomarkers of exposure to persistent organic pollutants in environmental health: Comparison of lipid adjustment approaches in a case study related to endometriosis.

PubMed

Cano-Sancho, German; Labrune, Léa; Ploteau, Stéphane; Marchand, Philippe; Le Bizec, Bruno; Antignac, Jean-Philippe

2018-06-01

The gold-standard matrix for measuring the internal levels of persistent organic pollutants (POPs) is the adipose tissue, however in epidemiological studies the use of serum is preferred due to the low cost and higher accessibility. The interpretation of serum biomarkers is tightly related to the understanding of the underlying causal structure relating the POPs, serum lipids and the disease. Considering the extended benefits of using serum biomarkers we aimed to further examine if through statistical modelling we would be able to improve the use and interpretation of serum biomarkers in the study of endometriosis. Hence, we have conducted a systematic comparison of statistical approaches commonly used to lipid-adjust the circulating biomarkers of POPs based on existing methods, using data from a pilot case-control study focused on severe deep infiltrating endometriosis. The odds ratios (ORs) obtained from unconditional regression for those models with serum biomarkers were further compared to those obtained from adipose tissue. The results of this exploratory study did not support the use of blood biomarkers as proxy estimates of POPs in adipose tissue to implement in risk models for endometriosis with the available statistical approaches to correct for lipids. The current statistical approaches commonly used to lipid-adjust circulating POPs, do not fully represent the underlying biological complexity between POPs, lipids and disease (especially those directly or indirectly affecting or affected by lipid metabolism). Hence, further investigations are warranted to improve the use and interpretation of blood biomarkers under complex scenarios of lipid dynamics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Southern Hemisphere origins for interannual variations of Tibetan Plateau snow cover in boreal summer

NASA Astrophysics Data System (ADS)

Wu, Z.

2017-12-01

The climate response to the Tibetan Plateau (TP) snow cover (TPSC) has been receiving extensive concern. However, relatively few studies have devoted to revealing the potential factors that can contribute to the TPSC variability on the interannual time scale. Especially during the boreal summer, snow cover can persist over the TP at high elevations, which exerts profound influences on the local and remote climate change. The present study finds that May Southern Hemisphere (SH) annular mode (SAM), the dominating mode of atmospheric circulation variability in the SH extratropics, exhibits a significant positive relationship with the boreal summer TPSC interannual variability. Observational analysis and numerical experiments manifest that the signal of May SAM can be "prolonged" by a meridional Indian Ocean tripole (IOT) sea surface temperature anomaly (SSTA) via atmosphere-ocean interaction. The IOT SSTA pattern persists into the following summer and excites anomalous local-scale zonal vertical circulation. Subsequently, a positive (or negative) tropical dipole rainfall (TDR) mode is induced with deficient (or sufficient) precipitation in tropical western Indian Ocean and sufficient (or deficient) precipitation in eastern Indian Ocean-Maritime continent. Rossby wave source diagnosis reveals that the wave energies, generated by the latent heat release of the TDR mode, propagate northward into western TP. As a response, abnormal cyclonic circulation and upward movement are triggered and prevail over western TP, providing favorable dynamical conditions for more TPSC, and vice versa. Hence, the IOT SSTA plays an "ocean bridge" role and the TDR mode acts as an "atmosphere bridge" role in the process of May SAM impacting the following summer TPSC variability. The results of our work may provide new insight about the cross-equatorial propagation of the SAM influence. Keywords Southern Hemisphere annular mode; Tibetan Plateau snow cover; Rossby wave source

Dynamics of Extreme Floods in Southeast and South Brazil

NASA Astrophysics Data System (ADS)

Ribeiro Lima, C. H.; Lall, U.

2015-12-01

Many extreme floods result from a causal chain, where exceptional rain and floods in water basins from different sizes are related to large scale, anomalous and persistent patterns in atmospheric and oceanic circulation. Organized moisture plumes from oceanic sources are often implicated. One could use an Eulerian-Lagrangian climate model to test a causal chain hypothesis, but the parameterization and testing of such a model covering convection and transport continues to be a challenge. Consequently, empirical data based studies can be useful to establish the need to formally model such events using this approach. Here we consider two flood-prone regions in Southeast and South Brazil as case studies. A hypothesis of the causal chain of extreme floods in these regions is investigated by means of observed streamflow and reanalysis data and some machine learning tools. The signatures of the organization of the large scale atmospheric circulation in the days prior to the flood events are evaluated based on the integrated moisture flux and its divergence field and storm track data, so that a better understanding of the relations between the flood magnitude and duration, strength of moisture convergence and role of regional moisture recycling or teleconnected moisture is established. Persistent patterns and anomalies in the sea surface temperature (SST) field in the Pacific and Atlantic oceans that may be associated with disturbances in the atmospheric circulation and with the flood dynamics are investigated through composite analysis. Finally, machine learning algorithms for nonlinear dimension reduction are employed to visualize and understand some of the spatio-temporal patterns of the dominated climate variables in a reduced dimensional space. Prospects for prediction are discussed.

Surface Currents and Winds at the Delaware Bay Mouth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muscarella, P A; Barton, N P; Lipphardt, B L

2011-04-06

Knowledge of the circulation of estuaries and adjacent shelf waters has relied on hydrographic measurements, moorings, and local wind observations usually removed from the region of interest. Although these observations are certainly sufficient to identify major characteristics, they lack both spatial resolution and temporal coverage. High resolution synoptic observations are required to identify important coastal processes at smaller scales. Long observation periods are needed to properly sample low-frequency processes that may also be important. The introduction of high-frequency (HF) radar measurements and regional wind models for coastal studies is changing this situation. Here we analyze synoptic, high-resolution surface winds andmore » currents in the Delaware Bay mouth over an eight-month period (October 2007 through May 2008). The surface currents were measured by two high-frequency radars while the surface winds were extracted from a data-assimilating regional wind model. To illustrate the utility of these monitoring tools we focus on two 45-day periods which previously were shown to present contrasting pictures of the circulation. One, the low-outflow period is from 1 October through 14 November 2007; the other is the high-outflow period from 3 March through 16 April 2008. The large-scale characteristics noted by previous workers are clearly corroborated. Specifically the M2 tide dominates the surface currents, and the Delaware Bay outflow plume is clearly evident in the low frequency currents. Several new aspects of the surface circulation were also identified. These include a map of the spatial variability of the M2 tide (validating an earlier model study), persistent low-frequency cross-mouth flow, and a rapid response of the surface currents to a changing wind field. However, strong wind episodes did not persist long enough to set up a sustained Ekman response.« less

10 CFR Appendix I to Subpart B of... - Uniform Test Method for Measuring the Energy Consumption of Conventional Ranges, Conventional...

Code of Federal Regulations, 2014 CFR

2014-01-01

..., set the clock time to 3:23 and use the average power approach described in Section 5, Paragraph 5.3.2... circulates air internally or externally to the cooking product for a finite period of time after the end of... persist for an indefinite time. An indicator that only shows the user that the product is in the off...

Northern Arabian Sea Circulation - Autonomous Research: Optimal Planning Systems (NASCar-OPS)

DTIC Science & Technology

2015-09-30

vehicles ( gliders , drifters, floats, and/or wave- gliders ) - Provide guidance for persistent optimal sampling, including for long-duration observation...headings and relative operating speeds will be provided to the operational fleets of instruments and vehicles (e.g. gliders , drifters, floats or wave... gliders ). We plan to use models specific to vehicle types (floats, wave- gliders , etc.). We also plan to further parallelize and optimize our codes

Interhemispheric differences in ionospheric convection: Cluster EDI observations revisited

NASA Astrophysics Data System (ADS)

Förster, M.; Haaland, S.

2015-07-01

The interaction between the interplanetary magnetic field and the geomagnetic field sets up a large-scale circulation in the magnetosphere. This circulation is also reflected in the magnetically connected ionosphere. In this paper, we present a study of ionospheric convection based on Cluster Electron Drift Instrument (EDI) satellite measurements covering both hemispheres and obtained over a full solar cycle. The results from this study show that average flow patterns and polar cap potentials for a given orientation of the interplanetary magnetic field can be very different in the two hemispheres. In particular during southward directed interplanetary magnetic field conditions, and thus enhanced energy input from the solar wind, the measurements show that the southern polar cap has a higher cross polar cap potential. There are persistent north-south asymmetries, which cannot easily be explained by the influence of external drivers. These persistent asymmetries are primarily a result of the significant differences in the strength and configuration of the geomagnetic field between the Northern and Southern Hemispheres. Since the ionosphere is magnetically connected to the magnetosphere, this difference will also be reflected in the magnetosphere in the form of different feedback from the two hemispheres. Consequently, local ionospheric conditions and the geomagnetic field configuration are important for north-south asymmetries in large regions of geospace.

Association of mixed hematopoietic chimerism with elevated circulating autoantibodies and chronic graft-versus-host disease occurrence

PubMed Central

Perruche, Sylvain; Marandin, Aliette; Kleinclauss, François M.; Angonin, Régis; Fresnay, Stéphanie; Baron, Marie Hélène; Tiberghien, Pierre; Saas, Philippe

2006-01-01

Background Use of a reduced intensity conditioning regimen before an allogeneic hematopoietic cell transplantation is frequently associated with an early state of mixed hematopoietic chimerism. Such a co-existence of both host and donor hematopoietic cells may influence post-transplant alloreactivity and may affect the occurrence and severity of acute and chronic graft-versus-host disease (GVHD) as well as the intensity of the graft-versus-leukemia effect. Here we evaluated the relation between chimerism state after reduced intensity conditioning transplantation (RICT), auto-antibody production and chronic GVHD (cGVHD)-related pathology. Methods Chimerism state, circulating anti-cardiolipin and anti-double stranded DNA auto-antibody (Ab) titers as well as occurrence of cGVHD-like lesions were investigated in a murine RICT model. Results We observed a novel association between mixed chimerism state, high levels of pathogenic IgG auto-Abs and subsequent development of cGVHD-like lesions. Furthermore, we found that the persistence of host B cells, but not dendritic cell origin or subset, was a factor associated with the appearance of cGVHD-like lesions. The implication of host B cells was confirmed by a host origin of auto-Abs. Conclusions Recipient B cell persistence may therefore contribute to the frequency and/or severity of cGVHD after RICT. PMID:16495806

The distribution of persistent organic pollutants in a trophically complex Antarctic ecosystem model

NASA Astrophysics Data System (ADS)

Bates, Michael L.; Bengtson Nash, Susan M.; Hawker, Darryl W.; Shaw, Emily C.; Cropp, Roger A.

2017-06-01

Despite Antarctica's isolation from human population centres, persistent organic pollutants (POPs) are transported there via long range atmospheric transport and subsequently cold-trapped. The challenging nature of working in the Antarctic environment greatly limits our ability to monitor POP concentrations and understand the processes that govern the distribution of POPs in Antarctic ecosystems. Here we couple a dynamic, trophically complex biological model with a fugacity model to investigate the distribution of hexachlorobenzene (HCB) in a near-shore Antarctic ecosystem. Using this model we examine the steady-state, and annual cycle of HCB concentration in the atmosphere, ocean, sediment, detritus, and 21 classes of biota that span from primary producers to apex predators. The scope and trophic resolution of our model allows us to examine POP pathways through the ecosystem. In our model the main pathway of HCB to upper trophic species is via pelagic communities, with relatively little via benthic communities. Using a dynamic ecosystem model also allows us to examine the seasonal and potential climate change induced changes in POP distribution. We show that there is a large annual cycle in concentration in the planktonic communities, which may have implications for biomagnification factors calculated from observations. We also examine the direct effects of increasing temperature on the redistribution of HCB in a changing climate and find that it is likely minor compared to other indirect effects, such as changes in atmospheric circulation, sea ice dynamics, and changes to the ecosystem itself.

Massive global ozone loss predicted following regional nuclear conflict

PubMed Central

Mills, Michael J.; Toon, Owen B.; Turco, Richard P.; Kinnison, Douglas E.; Garcia, Rolando R.

2008-01-01

We use a chemistry-climate model and new estimates of smoke produced by fires in contemporary cities to calculate the impact on stratospheric ozone of a regional nuclear war between developing nuclear states involving 100 Hiroshima-size bombs exploded in cities in the northern subtropics. We find column ozone losses in excess of 20% globally, 25–45% at midlatitudes, and 50–70% at northern high latitudes persisting for 5 years, with substantial losses continuing for 5 additional years. Column ozone amounts remain near or <220 Dobson units at all latitudes even after three years, constituting an extratropical “ozone hole.” The resulting increases in UV radiation could impact the biota significantly, including serious consequences for human health. The primary cause for the dramatic and persistent ozone depletion is heating of the stratosphere by smoke, which strongly absorbs solar radiation. The smoke-laden air rises to the upper stratosphere, where removal mechanisms are slow, so that much of the stratosphere is ultimately heated by the localized smoke injections. Higher stratospheric temperatures accelerate catalytic reaction cycles, particularly those of odd-nitrogen, which destroy ozone. In addition, the strong convection created by rising smoke plumes alters the stratospheric circulation, redistributing ozone and the sources of ozone-depleting gases, including N2O and chlorofluorocarbons. The ozone losses predicted here are significantly greater than previous “nuclear winter/UV spring” calculations, which did not adequately represent stratospheric plume rise. Our results point to previously unrecognized mechanisms for stratospheric ozone depletion. PMID:18391218

Circulating vaspin and visfatin are not affected by acute or chronic energy deficiency or leptin administration in humans.

PubMed

Kang, Eun Seok; Magkos, Faidon; Sienkiewicz, Elizabeth; Mantzoros, Christos S

2011-06-01

Animal and in vitro studies indicate that leptin alleviates starvation-induced reduction in circulating vaspin and stimulates the production of visfatin. We thus examined whether vaspin and visfatin are affected by short- and long-term energy deprivation and leptin administration in human subjects in vivo. We measured circulating levels of vaspin and visfatin i) before and after 72 h of starvation (leading to severe hypoleptinemia) with or without leptin administration in replacement doses in 13 normal-weight subjects, ii) before and after 72 h of starvation with leptin administration in pharmacological doses in 13 lean and obese subjects, iii) during chronic energy deficiency in eight women with hypothalamic amenorrhea on leptin replacement for 3 months, and iv) during chronic energy deficiency in 18 women with hypothalamic amenorrhea on leptin replacement or placebo for 3 months. Acute starvation decreased serum leptin to 21% of baseline values, (P=0.002) but had no significant effect on vaspin and visfatin concentrations (P>0.05). Nor did normalization of leptin levels affect the concentrations of these two adipokines (P>0.9). Leptin replacement in women with hypothalamic amenorrhea did not significantly alter vaspin and visfatin concentrations, whether relative to baseline or placebo administration (P>0.25). Pharmacological doses of leptin did not affect circulating vaspin and visfatin concentrations (P>0.9). Circulating vaspin and visfatin are not affected by acute or chronic energy deficiency leading to hypoleptinemia and are not regulated by leptin in human subjects, indicating that these adipocyte-secreted hormonal regulators of metabolism are independently regulated in humans.

Nonclinical evaluation of the serum pharmacodynamic biomarkers HGF and shed MET following dosing with the anti-MET monovalent monoclonal antibody onartuzumab.

PubMed

Mai, Elaine; Zheng, Zhong; Chen, Youjun; Peng, Jing; Severin, Christophe; Filvaroff, Ellen; Romero, Mally; Mallet, William; Kaur, Surinder; Gelzleichter, Thomas; Nijem, Ihsan; Merchant, Mark; Young, Judy C

2014-02-01

Onartuzumab, a humanized, monovalent monoclonal anti-MET antibody, antagonizes MET signaling by inhibiting binding of its ligand, hepatocyte growth factor (HGF). We investigated the effects of onartuzumab on cell-associated and circulating (shed) MET (sMET) and circulating HGF in vitro and nonclinically to determine their utility as pharmacodynamic biomarkers for onartuzumab. Effects of onartuzumab on cell-associated MET were assessed by flow cytometry and immunofluorescence. sMET and HGF were measured in cell supernatants and in serum or plasma from multiple species (mouse, cynomolgus monkey, and human) using plate-based immunoassays. Unlike bivalent anti-MET antibodies, onartuzumab stably associates with MET on the surface of cells without inducing MET internalization or shedding. Onartuzumab delayed the clearance of human xenograft tumor-produced sMET from the circulation of mice, and endogenous sMET in cynomolgus monkeys. In mice harboring MET-expressing xenograft tumors, in the absence of onartuzumab, levels of human sMET correlated with tumor size, and may be predictive of MET-expressing tumor burden. Because binding of sMET to onartuzumab in circulation resulted in increasing sMET serum concentrations due to reduced clearance, this likely renders sMET unsuitable as a pharmacodynamic biomarker for onartuzumab. There was no observed effect of onartuzumab on circulating HGF levels in xenograft tumor-bearing mice or endogenous HGF in cynomolgus monkeys. Although sMET and HGF may serve as predictive biomarkers for MET therapeutics, these data do not support their use as pharmacodynamic biomarkers for onartuzumab.

Post-Effect of Air Quality Improvement on Biomarkers for Systemic Inflammation and Microparticles in Asthma Patients After the 2008 Beijing Olympic Games: a Pilot Study.

PubMed

Gao, Jinming; Xu, Xiaohua; Ying, Zhekang; Jiang, Lei; Zhong, Mianhua; Wang, Aixia; Chen, Lung-Chi; Lu, Bo; Sun, Qinghua

2017-08-01

This study's aim was to investigate the post-effect of an air quality improvement on systemic inflammation and circulating microparticles in asthmatic patients during, and 2 months after, the Beijing Olympics 2008. We measured the levels of circulating inflammatory cytokines and microparticles in the peripheral blood from asthma patients and healthy controls during (phase 1), and 2 months after (phase 2) the Beijing 2008 Olympic Games. The concentrations of circulating cytokines (including TNFα, IL-6, IL-8, and IL-10) were still seen reduced in phase 2 when compared with those in phase 1. The number of circulating endothelial cell-derived microparticles was significantly lower during the phase 2 than that during phase 1 in asthma patients. The level of plasma lipopolysaccharide-binding protein (LBP) was significantly decreased in asthmatics in phase 2. The level of norepinephrine was significantly higher in phase 2 than that in phase 1 in plasma from both asthma patients and healthy subjects. There were no significant differences in the gene profile for the toll-like receptor (TLR) signaling from peripheral blood mononuclear cells. In vitro, microvesicles from patients with asthma impaired the relaxation to bradykinin and contraction to acetylcholine, whereas microparticles from healthy subjects did not. These data suggested that reduction in systemic pro-inflammatory responses and circulating LBP and increased level of norepinephrine in asthma patients persisted even after 2 months of the air pollution intervention. These changes were independent of the TLR signaling pathway. Circulating microparticles might be associated with airway smooth muscle dysfunction.

The Variability of the Horizontal Circulation in the Troposphere and Stratosphere: A Comparison

NASA Technical Reports Server (NTRS)

Perlwitz, Judith; Graf, Hans-F.; Hansem, James E. (Technical Monitor)

2001-01-01

The variability of the horizontal circulation in the stratosphere and troposphere of the Northern Hemisphere (NH) is compared by using various approaches. Spatial degrees of freedom (dof) on different time scales were derived. Modes of variability were computed in geopotential height fields at the tropospheric and stratospheric pressure levels by applying multivariate statistical approaches. Features of the spatial and temporal variability of the winterly zonal wind were studied with the help of recurrence and persistence analyses. The geopotential height and zonally-averaged zonal wind at the 50-, 500- and 1000-hPa level are used to investigate the behavior of the horizontal circulation in the lower stratosphere, mid-troposphere and at the near surface level, respectively. It is illustrated that the features of the variability of the horizontal circulation are very similar in the mid-troposphere and at the near surface level. Due to the filtering of tropospheric disturbances by the stratospheric and upper tropospheric zonal mean flow, the variability of the stratospheric circulation exhibits less spatial complexity than the circulation at tropospheric pressure levels. There exist enormous differences in the number of degrees of freedom (or free variability modes) between both atmospheric layers. Results of the analyses clearly show that the concept of a zonally symmetric AO with a simple structure in the troposphere similar to the one in the stratosphere is not valid. It is concluded that the spatially filtered climate change signal can be detected earlier in the stratosphere than in the mid-troposphere or at the near surface level.

Persistent babesiosis in a Rhesus macaque (Macaca mulatta) infected with a simian-human immunodeficiency virus

PubMed Central

Liu, David X.; Gill, Amy; Holman, Patricia J.; Didier, Peter J.; Blanchard, James L.; Veazey, Ronald S.; Lackner, Andrew A.

2014-01-01

A rhesus macaque developed persistent babesiosis following inoculation with a simian-human immunodeficiency virus. Blood smears demonstrated intraerythrocytic piroplasms and rare Maltese cross forms. Babesia microti-like protozoa were confirmed by PCR and gene sequence. With using nonhuman primates as models for human diseases, infection and complications from Babesia should be monitored. PMID:24517274

[Tissue oxygen saturation in the critically ill patient].

PubMed

Gruartmoner, G; Mesquida, J; Baigorri, F

2014-05-01

Hemodynamic resuscitation seeks to correct global macrocirculatory parameters of pressure and flow. However, current evidence has shown that despite the normalization of these global parameters, microcirculatory and regional perfusion alterations can persist, and these alterations have been independently associated with a poorer patient prognosis. This in turn has lead to growing interest in new technologies for exploring regional circulation and microcirculation. Near infra-red spectroscopy allows us to monitor tissue oxygen saturation, and has been proposed as a noninvasive, continuous and easy-to-obtain measure of regional circulation. The present review aims to summarize the existing evidence on near infra-red spectroscopy and its potential clinical role in the resuscitation of critically ill patients in shock. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Atmospheric Blocking and Atlantic Multi-Decadal Ocean Variability

NASA Technical Reports Server (NTRS)

Hakkinen, Sirpa; Rhines, Peter B.; Worthen, Denise L.

2011-01-01

Atmospheric blocking over the northern North Atlantic involves isolation of large regions of air from the westerly circulation for 5-14 days or more. From a recent 20th century atmospheric reanalysis (1,2) winters with more frequent blocking persist over several decades and correspond to a warm North Atlantic Ocean, in-phase with Atlantic multi-decadal ocean variability (AMV). Ocean circulation is forced by wind-stress curl and related air/sea heat exchange, and we find that their space-time structure is associated with dominant blocking patterns: weaker ocean gyres and weaker heat exchange contribute to the warm phase of AMV. Increased blocking activity extending from Greenland to British Isles is evident when winter blocking days of the cold years (1900-1929) are subtracted from those of the warm years (1939-1968).

Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells

DTIC Science & Technology

2014-10-01

AD_________________ Award Number: W81XWH-13-1-0325 TITLE: Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using ...Genetically Engineered Mouse Models and Human Circulating Tumor Cells PRINCIPAL INVESTIGATOR: Jeffrey Engelman MD PhD CONTRACTING ORGANIZATION ...Novel Therapeutic Approaches in Small Cell Lung 5a. CONTRACT NUMBER W81XWH-13-1-0325 Carcinoma Using Genetically Engineered Mouse Models and 5b

Persistent and energetic bottom-trapped topographic Rossby waves observed in the southern South China Sea.

PubMed

Shu, Yeqiang; Xue, Huijie; Wang, Dongxiao; Chai, Fei; Xie, Qiang; Cai, Shuqun; Chen, Rongyu; Chen, Ju; Li, Jian; He, Yunkai

2016-04-14

Energetic fluctuations with periods of 9-14 days below a depth of 1400 m were observed in the southern South China Sea (SCS) from 5 years of direct measurements. We interpreted such fluctuations as topographic Rossby waves (TRWs) because they obey the dispersion relation. The TRWs persisted from May 24, 2009 to August 23, 2013, and their bottom current speed with a maximum of ~10 cm/s was one order of magnitude greater than the mean current and comparable to the tidal currents near the bottom. The bottom-trapped TRWs had an approximate trapping depth of 325 m and reference wavelength of ~82 km, which were likely excited by eddies above. Upper layer current speed that peaked approximately every 2 months could offer the energy sources for the persistent TRWs in the southern SCS. Energetic bottom-trapped TRWs may have a comparable role in deep circulation to tides in areas with complex topography.

Persistent and energetic bottom-trapped topographic Rossby waves observed in the southern South China Sea

PubMed Central

Shu, Yeqiang; Xue, Huijie; Wang, Dongxiao; Chai, Fei; Xie, Qiang; Cai, Shuqun; Chen, Rongyu; Chen, Ju; Li, Jian; He, Yunkai

2016-01-01

Energetic fluctuations with periods of 9–14 days below a depth of 1400 m were observed in the southern South China Sea (SCS) from 5 years of direct measurements. We interpreted such fluctuations as topographic Rossby waves (TRWs) because they obey the dispersion relation. The TRWs persisted from May 24, 2009 to August 23, 2013, and their bottom current speed with a maximum of ~10 cm/s was one order of magnitude greater than the mean current and comparable to the tidal currents near the bottom. The bottom-trapped TRWs had an approximate trapping depth of 325 m and reference wavelength of ~82 km, which were likely excited by eddies above. Upper layer current speed that peaked approximately every 2 months could offer the energy sources for the persistent TRWs in the southern SCS. Energetic bottom-trapped TRWs may have a comparable role in deep circulation to tides in areas with complex topography. PMID:27075644

Control of stress-induced persistent anxiety by an extra-amygdala septohypothalamic circuit

PubMed Central

Anthony, Todd E.; Dee, Nick; Bernard, Amy; Lerchner, Walter; Heintz, Nathaniel; Anderson, David J.

2014-01-01

The extended amygdala has dominated research on the neural circuitry of fear and anxiety, but the septo-hippocampal axis plays an important role as well. The lateral septum (LS) is thought to suppress fear and anxiety, through its outputs to the hypothalamus. However, this structure has not yet been dissected using modern tools. The type 2 CRF receptor (Crfr2) marks a subset of LS neurons, whose functional connectivity we have investigated using optogenetics. Crfr2+ cells include GABAergic projection neurons that connect with the anterior hypothalamus. Surprisingly, we find that these LS outputs enhance stress-induced behavioral measures of anxiety. Furthermore, transient activation of Crfr2+ neurons promotes, while inhibition suppresses, persistent anxious behaviors. LS Crfr2+ outputs also positively regulate circulating corticosteroid levels. These data identify a subset of LS projection neurons that promote, rather than suppress, stress-induced behavioral and endocrinological dimensions of persistent anxiety states, and provide a cellular point-of-entry to LS circuitry. PMID:24485458

The study of trypanosome species circulating in domestic animals in two human African trypanosomiasis foci of Côte d'Ivoire identifies pigs and cattle as potential reservoirs of Trypanosoma brucei gambiense

PubMed Central

N’Djetchi, Martial Kassi; Ilboudo, Hamidou; Koffi, Mathurin; Kaboré, Jacques; Kaboré, Justin Windingoudi; Kaba, Dramane; Courtin, Fabrice; Coulibaly, Bamoro; Fauret, Pierre; Kouakou, Lingué; Ravel, Sophie; Deborggraeve, Stijn; Solano, Philippe; De Meeûs, Thierry; Bucheton, Bruno

2017-01-01

Background Important control efforts have led to a significant reduction of the prevalence of human African trypanosomiasis (HAT) in Côte d’Ivoire, but the disease is still present in several foci. The existence of an animal reservoir of Trypanosoma brucei gambiense may explain disease persistence in these foci where animal breeding is an important source of income but where the prevalence of animal African trypanosomiasis (AAT) is unknown. The aim of this study was to identify the trypanosome species circulating in domestic animals in both Bonon and Sinfra HAT endemic foci. Methodology/Principal findings 552 domestic animals (goats, pigs, cattle and sheep) were included. Blood samples were tested for trypanosomes by microscopic observation, species-specific PCR for T. brucei sl, T. congolense, T. vivax and subspecies-specific PCR for T. b. gambiense and T. b. gambiense immune trypanolysis (TL). Infection rates varied significantly between animal species and were by far the highest in pigs (30%). T. brucei s.l was the most prevalent trypanosome species (13.7%) followed by T. congolense. No T. b. gambiense was identified by PCR while high TL positivity rates were observed using T. b. gambiense specific variants (up to 27.6% for pigs in the Bonon focus). Conclusion This study shows that domestic animals are highly infected by trypanosomes in the studied foci. This was particularly true for pigs, possibly due to a higher exposure of these animals to tsetse flies. Whereas T. brucei s.l. was the most prevalent species, discordant results were obtained between PCR and TL regarding T. b. gambiense identification. It is therefore crucial to develop better tools to study the epidemiological role of potential animal reservoir for T. b. gambiense. Our study illustrates the importance of “one health” approaches to reach HAT elimination and contribute to AAT control in the studied foci. PMID:29045405

Genome Sequences of Human Adenovirus 14 Isolates from Mild Respiratory Cases and a Fatal Pneumonia, Isolated during 2006-2007 Epidemics in North America

DTIC Science & Technology

2010-01-01

We also compare the genome sequences of the recent isolates with those of the prototype HAdV-14 that circulated in Eurasia 30 years ago and the...closely related sequence of HAdV-11a, which has been circulating in southeast Asia. Conclusions: The data suggest that the currently circulating strain of...both mild and severe outbreaks. We also compare the genome sequences of the recent isolates with those of the prototype HAdV-14 that circulated in

Are flood occurrences in Europe linked to specific atmospheric circulation types?

NASA Astrophysics Data System (ADS)

Prudhomme, C.; Genevier, M.

2009-04-01

Flood damages are amongst the most costly climate-related hazard damages, with annual average flood damage in Europe in the last few decades of around €4bn per year (Barredo, 2007). With such economic and sometimes human losses, it is important to improve our estimations of flood risk for time scales from a few months (for increased preparedness) and to several decades (necessary to establish long-term flood management strategies). This paper investigates links between the occurrence of flood events and the atmospheric circulation patterns that have prevailed in the days leading to the flood. With the recent advances in climate modelling, such links could be exploited to anticipate the extent of potential damages due to flood using seasonal atmospheric forecasts products or future climate projections. The research is undertaken at a pan-European scale and exploits latest research in automatic classification techniques developed within the EU research network COST733 Action. Daily flow data from over 450 sites were used, available from the Global Runoff Data Centre, the European Water Archive, the UK National River Flow Archive and the French Banque Hydro. The atmospheric circulation types were defined following the Objective GrossWetterLagen classification (OGWL) developed by (James, 2007) using the ERA-40 mslp re-analysis, similar to the Hess-Brezowsky subjective classification (Hess and Brezowsky, 1977). Flood events were here defined according to the peak-over-threshold method, selecting the highest independent peaks observed in streamflow time series. The association between flood and atmospheric circulation types is assessed using two indicators. The first indicator calculates the difference between the frequency of occurrence of a circulation type CTi during a flood event to that for any day, expressed in percent. The significance of the anomaly is assessed using the χ2 statistics. The second indicator measures the probability of finding at last k days of N* of CTi using historical frequencies of occurrence. N* represents the number of days preceding a flood when the atmospheric conditions could significantly influence flood production processes, and could be interpreted as an upper limit of the concentration time of the basin. This evaluates the persistence of an atmospheric circulation type CTi prior to a flood event, and the associated level of significance. The indicators are calculated at-site and discussed regionally. Results show significant links with two circulation types related to Cyclonic Westerly (Wz) and the Low over the British Isles (TB), while the anticyclonic north-westerly type (Nea) systematically doesn't occur before any flood event. References Barredo, J.I., 2007. Major flood disasters in Europe: 1950-2005. Natural Hazards and Earth System Sciences, 42 doi: 10.1007/s11069-006-9065-2: 125-148. Hess, P. and Brezowsky, H., 1977. Katalog der Grobwetterlagen Europas 1881-1976. 3 verbesserte und ergäntze Auflage. Ber Dt. Wetterd. 15 (113). James, P.M., 2007. An objective classification method for Hess and Brezowsky Grosswetterlagen over Europe. Theoretical and Applied Climatology, 88(1): 17-42.

Prolonged Exposure of Primary Human Muscle Cells to Plasma Fatty Acids Associated with Obese Phenotype Induces Persistent Suppression of Muscle Mitochondrial ATP Synthase β Subunit.

PubMed

Tran, Lee; Hanavan, Paul D; Campbell, Latoya E; De Filippis, Elena; Lake, Douglas F; Coletta, Dawn K; Roust, Lori R; Mandarino, Lawrence J; Carroll, Chad C; Katsanos, Christos S

2016-01-01

Our previous studies show reduced abundance of the β-subunit of mitochondrial H+-ATP synthase (β-F1-ATPase) in skeletal muscle of obese individuals. The β-F1-ATPase forms the catalytic core of the ATP synthase, and it is critical for ATP production in muscle. The mechanism(s) impairing β-F1-ATPase metabolism in obesity, however, are not completely understood. First, we studied total muscle protein synthesis and the translation efficiency of β-F1-ATPase in obese (BMI, 36±1 kg/m2) and lean (BMI, 22±1 kg/m2) subjects. Both total protein synthesis (0.044±0.006 vs 0.066±0.006%·h-1) and translation efficiency of β-F1-ATPase (0.0031±0.0007 vs 0.0073±0.0004) were lower in muscle from the obese subjects when compared to the lean controls (P<0.05). We then evaluated these same responses in a primary cell culture model, and tested the specific hypothesis that circulating non-esterified fatty acids (NEFA) in obesity play a role in the responses observed in humans. The findings on total protein synthesis and translation efficiency of β-F1-ATPase in primary myotubes cultured from a lean subject, and after exposure to NEFA extracted from serum of an obese subject, were similar to those obtained in humans. Among candidate microRNAs (i.e., non-coding RNAs regulating gene expression), we identified miR-127-5p in preventing the production of β-F1-ATPase. Muscle expression of miR-127-5p negatively correlated with β-F1-ATPase protein translation efficiency in humans (r = - 0.6744; P<0.01), and could be modeled in vitro by prolonged exposure of primary myotubes derived from the lean subject to NEFA extracted from the obese subject. On the other hand, locked nucleic acid inhibitor synthesized to target miR-127-5p significantly increased β-F1-ATPase translation efficiency in myotubes (0.6±0.1 vs 1.3±0.3, in control vs exposure to 50 nM inhibitor; P<0.05). Our experiments implicate circulating NEFA in obesity in suppressing muscle protein metabolism, and establish impaired β-F1-ATPase translation as an important consequence of obesity.

Synthesis study of an erosion hot spot, Ocean Beach, California

USGS Publications Warehouse

Barnard, Patrick L.; Hansen, Jeff E.; Erikson, Li H.

2012-01-01

A synthesis of multiple coastal morphodynamic research efforts is presented to identify the processes responsible for persistent erosion along a 1-km segment of 7-km-long Ocean Beach in San Francisco, California. The beach is situated adjacent to a major tidal inlet and in the shadow of the ebb-tidal delta at the mouth of San Francisco Bay. Ocean Beach is exposed to a high-energy wave climate and significant alongshore variability in forcing introduced by varying nearshore bathymetry, tidal forcing, and beach morphology (e.g., beach variably backed by seawall, dunes, and bluffs). In addition, significant regional anthropogenic factors have influenced sediment supply and tidal current strength. A variety of techniques were employed to investigate the erosion at Ocean Beach, including historical shoreline and bathymetric analysis, monthly beach topographic surveys, nearshore and regional bathymetric surveys, beach and nearshore grain size analysis, two surf-zone hydrodynamic experiments, four sets of nearshore wave and current experiments, and several numerical modeling approaches. Here, we synthesize the results of 7 years of data collection to lay out the causes of persistent erosion, demonstrating the effectiveness of integrating an array of data sets covering a huge range of spatial scales. The key findings are as follows: anthropogenic influences have reduced sediment supply from San Francisco Bay, leading to pervasive contraction (i.e., both volume and area loss) of the ebb-tidal delta, which in turn reduced the regional grain size and modified wave focusing patterns along Ocean Beach, altering nearshore circulation and sediment transport patterns. In addition, scour associated with an exposed sewage outfall pipe causes a local depression in wave heights, significantly modifying nearshore circulation patterns that have been shown through modeling to be key drivers of persistent erosion in that area.

Circulating Tumor Cells and Response to Chemotherapy in Metastatic Breast Cancer: SWOG S0500

PubMed Central

Smerage, Jeffrey B.; Barlow, William E.; Hortobagyi, Gabriel N.; Winer, Eric P.; Leyland-Jones, Brian; Srkalovic, Gordan; Tejwani, Sheela; Schott, Anne F.; O'Rourke, Mark A.; Lew, Danika L.; Doyle, Gerald V.; Gralow, Julie R.; Livingston, Robert B.; Hayes, Daniel F.

2014-01-01

Purpose Increased circulating tumor cells (CTCs; five or more CTCs per 7.5 mL of whole blood) are associated with poor prognosis in metastatic breast cancer (MBC). A randomized trial of patients with persistent increase in CTCs tested whether changing chemotherapy after one cycle of first-line chemotherapy would improve the primary outcome of overall survival (OS). Patients and Methods Patients with MBC who did not have increased CTCs at baseline remained on initial therapy until progression (arm A). Patients with initially increased CTCs that decreased after 21 days of therapy remained on initial therapy (arm B). Patients with persistently increased CTCs after 21 days of therapy were randomly assigned to continue initial therapy (arm C1) or change to an alternative chemotherapy (arm C2). Results Of 595 eligible and evaluable patients, 276 (46%) did not have increased CTCs (arm A). Of those with initially increased CTCs, 31 (10%) were not retested, 165 were assigned to arm B, and 123 were randomly assigned to arm C1 or C2. No difference in median OS was observed between arm C1 and C2 (10.7 and 12.5 months, respectively; P = .98). CTCs were strongly prognostic. Median OS for arms A, B, and C (C1 and C2 combined) were 35 months, 23 months, and 13 months, respectively (P < .001). Conclusion This study confirms the prognostic significance of CTCs in patients with MBC receiving first-line chemotherapy. For patients with persistently increased CTCs after 21 days of first-line chemotherapy, early switching to an alternate cytotoxic therapy was not effective in prolonging OS. For this population, there is a need for more effective treatment than standard chemotherapy. PMID:24888818

Cardiac Ischemia Reperfusion Injury Following Instillation of 20 nm Citrate-capped Nanosilver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Becak DP, Holland NA; Shannahan, Jonathan H.

Background: Silver nanoparticles (AgNP) have garnered much interest due to their antimicrobial properties, becoming one of the most utilized nano scale materials. However, any potential evocable cardiovascular injury associated with exposure has not been previously reported. We have previously demonstrated expansion of myocardial infarction after intratracheal (IT) instillation of other nanomaterials. We hypothesized that pulmonary exposure to Ag core AgNP induces persistent increase in circulating cytokines, expansion of cardiac ischemia-reperfusion (I/R) injury and associated with altered coronary vessel reactivity. Methods: Male Sprague-Dawley rats were exposed to 200 µg of 20 nm citrate capped Ag core AgNP, or a citrate vehiclemore » intratracheally (IT). One and 7 days following IT instillation lungs were evaluated for inflammation and silver presence, serum was analyzed for concentrations of selected cytokines, and cardiac I/R injury and coronary artery reactivity was assessed. Results: AgNP instillation resulted in modest pulmonary injury with detection of silver in lung tissue and infiltrating cells, elevation of serum cytokines: G-CSF, MIP-1α, IL-1β, IL-2, IL-6, IL-13, IL-10, IL-18, IL-17, TNFα, and RANTES, expansion of I/R injury and depression of the coronary vessel reactivity at 1 day post IT compared to vehicle treated rats. Seven days post IT instillation was associated with persistent detection of silver in lungs, elevation in cytokines: IL-2, IL-13, and TNFα and expansion of I/R injury. Conclusions: Based on these data, IT instillation of AgNP increases circulating levels of several cytokines, which may contribute to persistent expansion of I/R injury possibly through an impaired vascular responsiveness.« less

PERSISTENT CONTAMINANTS: NEW PRIORITIES, NEW CONCERNS

EPA Science Inventory

The Stockholm Convention on persistent organic pollutants (POPs) was adopted in 2001 to protect human health and the environment from chemicals that are highly toxic, persistent, bioaccumulative, and undergo long range transport. These POPs include 9 pesticides, polychlorin...

Bisphenol A alters early oogenesis and follicle formation in the fetal ovary of the rhesus monkey

PubMed Central

Hunt, Patricia A.; Lawson, Crystal; Gieske, Mary; Murdoch, Brenda; Smith, Helen; Marre, Alyssa; Hassold, Terry; VandeVoort, Catherine A.

2012-01-01

Widespread use of the endocrine disrupting chemical bisphenol A (BPA) in consumer products has resulted in nearly continuous human exposure. In rodents, low-dose exposures have been reported to adversely affect two distinct stages of oogenesis in the developing ovary: the events of prophase at the onset of meiosis in the fetal ovary and the formation of follicles in the perinatal ovary. Because these effects could influence the reproductive longevity and success of the exposed individual, we conducted studies in the rhesus monkey to determine whether BPA induces similar disturbances in the developing primate ovary. The routes and levels of human exposure are unclear; hence, two different exposure protocols were used: single daily oral doses and continuous exposure via subdermal implant. Our analyses of second trimester fetuses exposed at the time of meiotic onset suggest that, as in mice, BPA induces subtle disturbances in the prophase events that set the stage for chromosome segregation at the first meiotic division. Our analyses of third-trimester fetuses exposed to single daily oral doses during the time of follicle formation revealed an increase in multioocyte follicles analogous to that reported in rodents. However, two unique phenotypes were evident in continuously exposed animals: persistent unenclosed oocytes in the medullary region and small, nongrowing oocytes in secondary and antral follicles. Because effects on both stages of oogenesis were elicited using doses that yield circulating levels of BPA analogous to those reported in humans, these findings raise concerns for human reproductive health. PMID:23012422

Persistent poliovirus infection of human fetal brain cells.

PubMed

Pavio, N; Buc-Caron, M H; Colbère-Garapin, F

1996-09-01

It has been suggested that poliovirus (PV), the causative agent of poliomyelitis, could persist in surviving patients. We have previously shown that PV can persistently infect some human cell lines in vitro, particularly neuroblastoma cell lines. We report here an ex vivo model in which PV can persistently infect primary cultures of human fetal brain cells. Two mutations involving capsid residues 142 of VP2 and 95 of VP1 were repeatedly selected during the persistent infections. These residues are located in capsid regions known to be involved in interactions between PV and its receptor. During the first week after infection, viral antigens were found in cells of both the neuronal and glial lineages. In contrast, 2 weeks after infection, viral antigens were detected almost exclusively in cells of the neuronal lineage. They were detected predominantly in cells expressing a marker of early commitment to the neuronal lineage, MAP-5, particularly in neuroblasts. Viral antigens were also found in immature progenitors expressing a neuroepithelium marker, nestin, and in cells expressing a marker of postmitotic neurons, MAP-2. The presence of viral antigens in postmitotic neurons suggests that PV can persist in neurons of patients who have survived poliomyelitis.

Uncarboxylated matrix Gla protein (ucMGP) is associated with coronary artery calcification in haemodialysis patients.

PubMed

Cranenburg, Ellen C M; Brandenburg, Vincent M; Vermeer, Cees; Stenger, Melanie; Mühlenbruch, Georg; Mahnken, Andreas H; Gladziwa, Ulrich; Ketteler, Markus; Schurgers, Leon J

2009-02-01

Matrix gamma-carboxyglutamate (Gla) protein (MGP) is a potent local inhibitor of cardiovascular calcification and accumulates at areas of calcification in its uncarboxylated form (ucMGP). We previously found significantly lower circulating ucMGP levels in patients with a high vascular calcification burden. Here we report on the potential of circulating ucMGP to serve as a biomarker for vascular calcification in haemodialysis (HD) patients. Circulating ucMGP levels were measured with an ELISA-based assay in 40 HD patients who underwent multi-slice computed tomography (MSCT) scanning to quantify the extent of coronary artery calcification (CAC). The mean ucMGP level in HD patients (193 +/- 65 nM) was significantly lower as compared to apparently healthy subjects of the same age (441 +/- 97 nM; p < 0.001) and patients with rheumatoid arthritis (RA) without CAC (560 +/- 140 nM; p < 0.001). Additionally, ucMGP levels correlated inversely with CAC scores (r = -0.41; p = 0.009), and this correlation persisted after adjustment for age, dialysis vintage and high-sensitivity C-reactive protein (hs-CRP). Since circulating ucMGP levels are significantly and inversely correlated with the extent of CAC in HD patients, ucMGP may become a tool for identifying HD patients with a high probability of cardiovascular calcification.

Global circulation as the main source of cloud activity on Titan

USGS Publications Warehouse

Rodriguez, S.; Le, Mouelic S.; Rannou, P.; Tobie, G.; Baines, K.H.; Barnes, J.W.; Griffith, C.A.; Hirtzig, M.; Pitman, K.M.; Sotin, Christophe; Brown, R.H.; Buratti, B.J.; Clark, R.N.; Nicholson, P.D.

2009-01-01

Clouds on Titan result from the condensation of methane and ethane and, as on other planets, are primarily structured by circulation of the atmosphere. At present, cloud activity mainly occurs in the southern (summer) hemisphere, arising near the pole and at mid-latitudes from cumulus updrafts triggered by surface heating and/or local methane sources, and at the north (winter) pole, resulting from the subsidence and condensation of ethane-rich air into the colder troposphere. General circulation models predict that this distribution should change with the seasons on a 15-year timescale, and that clouds should develop under certain circumstances at temperate latitudes (40??) in the winter hemisphere. The models, however, have hitherto been poorly constrained and their long-term predictions have not yet been observationally verified. Here we report that the global spatial cloud coverage on Titan is in general agreement with the models, confirming that cloud activity is mainly controlled by the global circulation. The non-detection of clouds at latitude 40??N and the persistence of the southern clouds while the southern summer is ending are, however, both contrary to predictions. This suggests that Titans equator-to-pole thermal contrast is overestimated in the models and that its atmosphere responds to the seasonal forcing with a greater inertia than expected. ?? 2009 Macmillan Publishers Limited. All rights reserved.

Persistence of Antibody in Health Care Workers Vaccinated Against Hepatitis B: A Study on Vaccine Effectiveness Over Time

DTIC Science & Technology

1994-05-01

the single most important cause of persistent viremia in humans. The HBV is responsible for approximately 80% of cases of primary hepatocellular ... carcinoma and is second only to tobacco in its importance as a known human carcinogen

High-Mobility Group Box 1 From Hypoxic Trophoblasts Promotes Endothelial Microparticle Production and Thrombophilia in Preeclampsia.

PubMed

Hu, Yae; Yan, Ruhong; Zhang, Ce; Zhou, Zhichao; Liu, Meng; Wang, Can; Zhang, Hong; Dong, Liang; Zhou, Tiantian; Wu, Yi; Dong, Ningzheng; Wu, Qingyu

2018-04-12

Thrombophilia is a major complication in preeclampsia, a disease associated with placental hypoxia and trophoblast inflammation. Preeclampsia women are known to have increased circulating microparticles that are procoagulant, but the underlying mechanisms remain unclear. In this study, we sought to understand the mechanism connecting placental hypoxia, circulating microparticles, and thrombophilia. We analyzed protein markers on plasma microparticles from preeclampsia women and found that the increased circulating microparticles were mostly from endothelial cells. In proteomic studies, we identified HMGB1 (high-mobility group box 1), a proinflammatory protein, as a key factor from hypoxic trophoblasts in stimulating microparticle production in human umbilical vein endothelial cells. Immunodepletion or inhibition of HMGB1 in the conditioned medium from hypoxic human trophoblasts abolished the endothelial microparticle-stimulating activity. Conversely, recombinant HMGB1 stimulated microparticle production in cultured human umbilical vein endothelial cells. The microparticles from recombinant HMGB1-stimulated human umbilical vein endothelial cells promoted blood coagulation and neutrophil activation in vitro. Injection of recombinant HMGB1 in pregnant mice increased plasma endothelial microparticles and promoted blood coagulation. In preeclampsia women, elevated placental HMGB1 expression was detected and high levels of plasma HMGB1 correlated with increased plasma endothelial microparticles. Our results indicate that placental hypoxia-induced HMGB1 expression and release from trophoblasts are important mechanism underlying increased circulating endothelial microparticles and thrombophilia in preeclampsia. © 2018 American Heart Association, Inc.

Aging and cytomegalovirus (CMV) infection differentially and jointly affect distinct circulating T cell subsets in humans1

PubMed Central

Wertheimer, Anne M.; Bennett, Michael S.; Park, Byung; Uhrlaub, Jennifer L.; Martinez, Carmine; Pulko, Vesna; Currier, Noreen L.; Nikolich-Zugich, Dragana; Kaye, Jeffrey; Nikolich-Zugich, Janko

2014-01-01

The impact of intrinsic aging upon human peripheral blood T-cell subsets remains incompletely quantified and understood. This impact must be distinguished from the influence of latent persistent microorganisms, particularly cytomegalovirus (CMV), which has been associated with age-related changes in the T cell pool. In a cross-sectional cohort of 152 CMV-negative individuals, aged 21–101 years, we found that aging correlated strictly to an absolute loss of naïve CD8, but not CD4, T cells, but, contrary to many reports, did not lead to an increase in memory T cell numbers. The loss of naïve CD8 T cells was not altered by CMV in 239 subjects (range 21–96 years) but the decline in CD4+ naïve cells showed significance in CMV+ individuals. These individuals also exhibited an absolute increase in the effector/effector memory CD4+ and CD8+ cells with age. That increase was seen mainly, if not exclusively, in older subjects with elevated anti-CMV Ab titers, suggesting that efficacy of viral control over time may determine the magnitude of CMV impact upon T cell memory, and perhaps upon immune defense. These findings provide important new insights into the age-related changes in the peripheral blood pool of older adults, demonstrating that aging and CMV exert both distinct and joint influence upon blood T cell homeostasis in humans. PMID:24501199

Durable engraftment of genetically modified FVIII-secreting autologous bone marrow stromal cells in the intramedullary microenvironment.

PubMed

Lee, Sze Sing; Sivalingam, Jaichandran; Nirmal, Ajit J; Ng, Wai Har; Kee, Irene; Song, In Chin; Kiong, Chin Yong; Gales, Kristoffer A; Chua, Frederic; Pena, Edgar M; Ogden, Bryan E; Kon, Oi Lian

2018-04-23

Genetically modified FVIII-expressing autologous bone marrow-derived mesenchymal stromal cells (BMSCs) could cure haemophilia A. However, culture-expanded BMSCs engraft poorly in extramedullary sites. Here, we compared the intramedullary cavity, skeletal muscle, subcutaneous tissue and systemic circulation as tissue microenvironments that could support durable engraftment of FVIII-secreting BMSC in vivo. A zinc finger nuclease integrated human FVIII transgene into PPP1R12C (intron 1) of culture-expanded primary canine BMSCs. FVIII-secretory capacity of implanted BMSCs in each dog was expressed as an individualized therapy index (number of viable BMSCs implanted × FVIII activity secreted/million BMSCs/24 hours). Plasma samples before and after implantation were assayed for transgenic FVIII protein using an anti-human FVIII antibody having negligible cross-reactivity with canine FVIII. Plasma transgenic FVIII persisted for at least 48 weeks after implantation in the intramedullary cavity. Transgenic FVIII protein levels were low after intramuscular implantation and undetectable after both intravenous infusion and subcutaneous implantation. All plasma samples were negative for anti-human FVIII antibodies. Plasma concentrations and durability of transgenic FVIII secretion showed no correlation with the therapy index. Thus, the implantation site microenvironment is crucial. The intramedullary microenvironment, but not extramedullary tissues, supported durable engraftment of genetically modified autologous FVIII-secreting BMSCs. © 2018 National Cancer Centre of Singapore Pte Ltd. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs.

PubMed

Muñoz-González, Sara; Perez-Simó, Marta; Muñoz, Marta; Bohorquez, José Alejandro; Rosell, Rosa; Summerfield, Artur; Domingo, Mariano; Ruggli, Nicolas; Ganges, Llilianne

2015-07-09

Classical swine fever (CSF) causes major losses in pig farming, with various degrees of disease severity. Efficient live attenuated vaccines against classical swine fever virus (CSFV) are used routinely in endemic countries. However, despite intensive vaccination programs in these areas for more than 20 years, CSF has not been eradicated. Molecular epidemiology studies in these regions suggests that the virus circulating in the field has evolved under the positive selection pressure exerted by the immune response to the vaccine, leading to new attenuated viral variants. Recent work by our group demonstrated that a high proportion of persistently infected piglets can be generated by early postnatal infection with low and moderately virulent CSFV strains. Here, we studied the immune response to a hog cholera lapinised virus vaccine (HCLV), C-strain, in six-week-old persistently infected pigs following post-natal infection. CSFV-negative pigs were vaccinated as controls. The humoral and interferon gamma responses as well as the CSFV RNA loads were monitored for 21 days post-vaccination. No vaccine viral RNA was detected in the serum samples and tonsils from CSFV postnatally persistently infected pigs for 21 days post-vaccination. Furthermore, no E2-specific antibody response or neutralising antibody titres were shown in CSFV persistently infected vaccinated animals. Likewise, no of IFN-gamma producing cell response against CSFV or PHA was observed. To our knowledge, this is the first report demonstrating the absence of a response to vaccination in CSFV persistently infected pigs.

Numerical weather prediction in low latitudes

NASA Technical Reports Server (NTRS)

Krishnamurti, T. N.

1985-01-01

Based on the results of a number of numerical prediction experiments, the differential heating between land and ocean is an important and critical factor for investigation of phenomenon such as the onset of monsoons over the Indian subcontinent. The pre-onset period during the month of May shows a rather persistent flow field in the monsoon region. At low levels the circulation exhibits anticyclonic excursions over the Arabian Sea, flowing essentially parallel to the west coast of India from the north. Over the Indian subcontinent the major feature is a shallow heat low over northern India. As the heat sources commence a rapid northwestward movement toward the southern edge of the Tibetan Plateau, an interesting configuration of the large-scale divergent circulation occurs. A favorable configuration for a rapid exchange of energy from the divergent to the rotational kinetic energy develops. Strong low level monsoonal circulations evolve, attendant with that the onset of monsoon rains occurs. In order to test this observational sequence, a series of short-range numerical prediction experiments were initiated to define the initial heat sources.

Differential Persistence of Foot-and-Mouth Disease Virus in African Buffalo Is Related to Virus Virulence

PubMed Central

Maree, Francois; de Klerk-Lorist, Lin-Mari; Gubbins, Simon; Zhang, Fuquan; Seago, Julian; Pérez-Martín, Eva; Reid, Liz; Scott, Katherine; van Schalkwyk, Louis; Bengis, Roy; Juleff, Nicholas

2016-01-01

ABSTRACT Foot-and-mouth disease (FMD) virus (FMDV) circulates as multiple serotypes and strains in many regions of endemicity. In particular, the three Southern African Territories (SAT) serotypes are maintained effectively in their wildlife reservoir, the African buffalo, and individuals may harbor multiple SAT serotypes for extended periods in the pharyngeal region. However, the exact site and mechanism for persistence remain unclear. FMD in buffaloes offers a unique opportunity to study FMDV persistence, as transmission from carrier ruminants has convincingly been demonstrated for only this species. Following coinfection of naive African buffaloes with isolates of three SAT serotypes from field buffaloes, palatine tonsil swabs were the sample of choice for recovering infectious FMDV up to 400 days postinfection (dpi). Postmortem examination identified infectious virus for up to 185 dpi and viral genomes for up to 400 dpi in lymphoid tissues of the head and neck, focused mainly in germinal centers. Interestingly, viral persistence in vivo was not homogenous, and the SAT-1 isolate persisted longer than the SAT-2 and SAT-3 isolates. Coinfection and passage of these SAT isolates in goat and buffalo cell lines demonstrated a direct correlation between persistence and cell-killing capacity. These data suggest that FMDV persistence occurs in the germinal centers of lymphoid tissue but that the duration of persistence is related to virus replication and cell-killing capacity. IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in domestic livestock and wildlife species. African buffaloes (Syncerus caffer) are the primary carrier hosts of FMDV in African savannah ecosystems, where the disease is endemic. We have shown that the virus persists for up to 400 days in buffaloes and that there is competition between viruses during mixed infections. There was similar competition in cell culture: viruses that killed cells quickly persisted more efficiently in passaged cell cultures. These results may provide a mechanism for the dominance of particular viruses in an ecosystem. PMID:26962214

Population-Level Immune-Mediated Adaptation in HIV-1 Polymerase during the North American Epidemic

PubMed Central

Kinloch, Natalie N.; MacMillan, Daniel R.; Le, Anh Q.; Cotton, Laura A.; Bangsberg, David R.; Buchbinder, Susan; Carrington, Mary; Fuchs, Jonathan; Harrigan, P. Richard; Koblin, Beryl; Kushel, Margot; Markowitz, Martin; Mayer, Kenneth; Milloy, M. J.; Schechter, Martin T.; Wagner, Theresa; Walker, Bruce D.; Carlson, Jonathan M.; Poon, Art F. Y.

2015-01-01

ABSTRACT Human leukocyte antigen (HLA) class I-associated polymorphisms in HIV-1 that persist upon transmission to HLA-mismatched hosts may spread in the population as the epidemic progresses. Transmission of HIV-1 sequences containing such adaptations may undermine cellular immune responses to the incoming virus in future hosts. Building upon previous work, we investigated the extent of HLA-associated polymorphism accumulation in HIV-1 polymerase (Pol) through comparative analysis of linked HIV-1/HLA class I genotypes sampled during historic (1979 to 1989; n = 338) and modern (2001 to 2011; n = 278) eras from across North America (Vancouver, BC, Canada; Boston, MA; New York, NY; and San Francisco, CA). Phylogenies inferred from historic and modern HIV-1 Pol sequences were star-like in shape, with an inferred most recent common ancestor (epidemic founder virus) sequence nearly identical to the modern North American subtype B consensus sequence. Nevertheless, modern HIV-1 Pol sequences exhibited roughly 2-fold-higher patristic (tip-to-tip) genetic distances than historic sequences, with HLA pressures likely driving ongoing diversification. Moreover, the frequencies of published HLA-associated polymorphisms in individuals lacking the selecting HLA class I allele was on average ∼2.5-fold higher in the modern than in the historic era, supporting their spread in circulation, though some remained stable in frequency during this time. Notably, polymorphisms restricted by protective HLA alleles appear to be spreading to a greater relative extent than others, though these increases are generally of modest absolute magnitude. However, despite evidence of polymorphism spread, North American hosts generally remain at relatively low risk of acquiring an HIV-1 polymerase sequence substantially preadapted to their HLA profiles, even in the present era. IMPORTANCE HLA class I-restricted cytotoxic T-lymphocyte (CTL) escape mutations in HIV-1 that persist upon transmission may accumulate in circulation over time, potentially undermining host antiviral immunity to the transmitted viral strain. We studied >600 experimentally collected HIV-1 polymerase sequences linked to host HLA information dating back to 1979, along with phylogenetically reconstructed HIV-1 sequences dating back to the virus' introduction into North America. Overall, our results support the gradual spread of many—though not all—HIV-1 polymerase immune escape mutations in circulation over time. This is consistent with recent observations from other global regions, though the extent of polymorphism accumulation in North America appears to be lower than in populations with high seroprevalence, older epidemics, and/or limited HLA diversity. Importantly, the risk of acquiring an HIV-1 polymerase sequence at transmission that is substantially preadapted to one's HLA profile remains relatively low in North America, even in the present era. PMID:26559841

Micro RNAs from DNA Viruses are Found Widely in Plasma in a Large Observational Human Population.

PubMed

Koupenova, Milka; Mick, Eric; Corkrey, Heather A; Huan, Tianxiao; Clancy, Lauren; Shah, Ravi; Benjamin, Emelia J; Levy, Daniel; Kurt-Jones, Evelyn A; Tanriverdi, Kahraman; Freedman, Jane E

2018-04-23

Viral infections associate with disease risk and select families of viruses encode miRNAs that control an efficient viral cycle. The association of viral miRNA expression with disease in a large human population has not been previously explored. We sequenced plasma RNA from 40 participants of the Framingham Heart Study (FHS, Offspring Cohort, Visit 8) and identified 3 viral miRNAs from 3 different human Herpesviridae. These miRNAs were mostly related to viral latency and have not been previously detected in human plasma. Viral miRNA expression was then screened in the plasma of 2763 participants of the remaining cohort utilizing high-throughput RT-qPCR. All 3 viral miRNAs associated with combinations of inflammatory or prothrombotic circulating biomarkers (sTNFRII, IL-6, sICAM1, OPG, P-selectin) but did not associate with hypertension, coronary heart disease or cancer. Using a large observational population, we demonstrate that the presence of select viral miRNAs in the human circulation associate with inflammatory biomarkers and possibly immune response, but fail to associate with overt disease. This study greatly extends smaller singular observations of viral miRNAs in the human circulation and suggests that select viral miRNAs, such as those for latency, may not impact disease manifestation.

Advances in the Diagnosis and Management of Persistent Pulmonary Hypertension of the Newborn (PPHN)

PubMed Central

Konduri, G. Ganesh; Kim, U. Olivia

2009-01-01

Synopsis Rapid evaluation of a neonate who is cyanotic and in respiratory distress is essential for achieving a good outcome. Persistent pulmonary hypertension of the newborn (PPHN) can be a primary cause or a contributing factor to respiratory failure, particularly in neonates born at ≥34 weeks gestation. PPHN represents a failure of normal postnatal adaptation that occurs at birth in the pulmonary circulation. Rapid advances in therapy in recent years have lead to a remarkable decrease in mortality for the affected infants. However, infants who survive PPHN are at a significant risk for long term hearing and neuro-developmental impairments. This review focuses on the diagnosis, recent advances in management and recommendations for the long term follow-up of infants with PPHN. PMID:19501693

Climate change and avian influenza

PubMed Central

Slingenbergh, J.; Xiao, X.

2009-01-01

Summary This paper discusses impacts of climate change on the ecology of avian influenza viruses (AI viruses), which presumably co-evolved with migratory water birds, with virus also persisting outside the host in subarctic water bodies. Climate change would almost certainly alter bird migration, influence the AI virus transmission cycle and directly affect virus survival outside the host. The joint, net effects of these changes are rather unpredictable, but it is likely that AI virus circulation in water bird populations will continue with endless adaptation and evolution. In domestic poultry, too little is known about the direct effect of environmental factors on highly pathogenic avian influenza transmission and persistence to allow inference about the possible effect of climate change. However, possible indirect links through changes in the distribution of duck-crop farming are discussed. PMID:18819672

Effect of human body weight changes on circulating levels of peptide YY and peptide YY3-36.

PubMed

Pfluger, P T; Kampe, J; Castaneda, T R; Vahl, T; D'Alessio, D A; Kruthaupt, T; Benoit, S C; Cuntz, U; Rochlitz, H J; Moehlig, M; Pfeiffer, A F H; Koebnick, C; Weickert, M O; Otto, B; Spranger, J; Tschöp, M H

2007-02-01

Recent findings suggest that low plasma peptide YY (PYY) levels may contribute to diet-induced human obesity and justify PYY replacement therapy. Although the pharmacological value of PYY is controversial, further study of the secretion of the precursor PYY(1-36) and the pharmacologically active PYY(3-36) is indicated to determine the potential role in energy balance regulation. Our objective was to determine the effects of acute and chronic changes in human body weight on circulating levels of the putative satiety hormone peptide YY. Total plasma PYY levels (PYY(1-36) + PYY(3-36)) were measured in 66 lean, 18 anorectic, 63 obese, and 16 morbidly obese humans. In addition, total PYY was measured in 17 of the obese patients after weight loss and in the 18 anorectic patients after weight gain. Fasting PYY(3-36) levels were measured in 17 lean and 15 obese individuals. Fasting total plasma PYY levels were highest in patients with anorexia nervosa (80.9 +/- 12.9 pg/ml, P < 0.05) compared with lean (52.4 +/- 4.6 pg/ml), obese (43.9 +/- 3.8 pg/ml), or morbidly obese (45.6 +/- 11.2 pg/ml) subjects. In obese patients, weight loss of 5.4% was associated with a 30% decrease in fasting total PYY plasma levels. In anorectic patients, weight gain had no effect on fasting PYY. PYY(3-36) levels did not differ between lean (96.2 +/- 8.6 pg/ml) and obese (91.5 +/- 6.9 pg/ml) subjects. Our findings do not support a role for abnormal circulating PYY in human obesity. We conclude that circulating PYY levels in humans are significantly elevated in anorexia nervosa and, given the controversially discussed anorectic effect of PYY, could theoretically contribute to that syndrome.

A Lower Olfactory Capacity Is Related to Higher Circulating Concentrations of Endocannabinoid 2-Arachidonoylglycerol and Higher Body Mass Index in Women.

PubMed

Pastor, Antoni; Fernández-Aranda, Fernando; Fitó, Montserrat; Jiménez-Murcia, Susana; Botella, Cristina; Fernández-Real, Jose M; Frühbeck, Gema; Tinahones, Francisco J; Fagundo, Ana B; Rodriguez, Joan; Agüera, Zaida; Langohr, Klaus; Casanueva, Felipe F; de la Torre, Rafael

2016-01-01

The endocannabinoid (eCB) system can promote food intake by increasing odor detection in mice. The eCB system is over-active in human obesity. Our aim is to measure circulating eCB concentrations and olfactory capacity in a human sample that includes people with obesity and explore the possible interaction between olfaction, obesity and the eCB system. The study sample was made up of 161 females with five groups of body mass index sub-categories ranging from under-weight to morbidly obese. We assessed olfactory capacity with the "Sniffin´Sticks" test, which measures olfactory threshold-discrimination-identification (TDI) capacity. We measured plasma concentrations of the eCBs 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine or anandamide (AEA), and several eCB-related compounds, 2-acylglycerols and N-acylethanolamines. 2-AG and other 2-acylglycerols fasting plasma circulating plasma concentrations were higher in obese and morbidly obese subjects. AEA and other N-acylethanolamine circulating concentrations were lower in under-weight subjects. Olfactory TDI scores were lower in obese and morbidly obese subjects. Lower TDI scores were independently associated with higher 2-AG fasting plasma circulating concentrations, higher %body fat, and higher body mass index, after controlling for age, smoking, menstruation, and use of contraceptives. Our results show that obese subjects have a lower olfactory capacity than non-obese ones and that elevated fasting plasma circulating 2-AG concentrations in obesity are linked to a lower olfactory capacity. In agreement with previous studies we show that eCBs AEA and 2-AG, and their respective congeners have a distinct profile in relation to body mass index. The present report is the first study in humans in which olfactory capacity and circulating eCB concentrations have been measured in the same subjects.

The pathogenic role of persistent milk signaling in mTORC1- and milk-microRNA-driven type 2 diabetes mellitus.

PubMed

Melnik, Bodo C

2015-01-01

Milk, the secretory product of the lactation genome, promotes growth of the newborn mammal. Milk delivers insulinotropic amino acids, thus maintains a molecular crosstalk with the pancreatic β-cell of the milk recipient. Homeostasis of β-cells and insulin production depend on the appropriate magnitude of mTORC1 signaling. mTORC1 is activated by branched-chain amino acids (BCAAs), glutamine, and palmitic acid, abundant nutrient signals of cow´s milk. Furthermore, milk delivers bioactive exosomal microRNAs. After milk consumption, bovine microRNA-29b, a member of the diabetogenic microRNA-29- family, reaches the systemic circulation and the cells of the milk consumer. MicroRNA-29b downregulates branchedchain α-ketoacid dehydrogenase, a potential explanation for increased BCAA serum levels, the metabolic signature of insulin resistance and type 2 diabetes mellitus (T2DM). In non-obese diabetic mice, microRNA-29b downregulates the antiapoptotic protein Mcl-1, which leads to early β-cell death. In all mammals except Neolithic humans, milk-driven mTORC1 signaling is physiologically restricted to the postnatal period. In contrast, chronic hyperactivated mTORC1 signaling has been associated with the development of age-related diseases of civilization including T2DM. Notably, chronic hyperactivation of mTORC1 enhances endoplasmic reticulum stress that promotes apoptosis. In fact, hyperactivated β-cell mTORC1 signaling induced early β-cell apoptosis in a mouse model. The EPIC-InterAct Study demonstrated an association between milk consumption and T2DM in France, Italy, United Kingdom, Germany, and Sweden. In contrast, fermented milk products and cheese exhibit an inverse correlation. Since the early 1950´s, refrigeration technology allowed widespread consumption of fresh pasteurized milk, which facilitates daily intake of bioactive bovine microRNAs. Persistent uptake of cow´s milk-derived microRNAs apparently transfers an overlooked epigenetic diabetogenic program that should not reach the human food chain.

Solid waste containing persistent organic pollutants in Serbia: From precautionary measures to the final treatment (case study).

PubMed

Stevanovic-Carapina, Hristina; Milic, Jelena; Curcic, Marijana; Randjelovic, Jasminka; Krinulovic, Katarina; Jovovic, Aleksandar; Brnjas, Zvonko

2016-07-01

Sustainable solid waste management needs more dedicated attention in respect of environmental and human health protection. Solid waste containing persistent organic pollutants is of special concern, since persistent organic pollutants are persistent, toxic and of high risk to human health and the environment. The objective of this investigation was to identify critical points in the Serbian system of solid waste and persistent organic pollutants management, to assure the life cycle management of persistent organic pollutants and products containing these chemicals, including prevention and final destruction. Data were collected from the Serbian competent authorities, and led us to identify preventive actions for solid waste management that should reduce or minimise release of persistent organic pollutants into the environment, and to propose actions necessary for persistent organic pollutants solid waste. The adverse impact of persistent organic pollutants is multidimensional. Owing to the lack of treatment or disposal plants for hazardous waste in Serbia, the only option at the moment to manage persistent organic pollutants waste is to keep it in temporary storage and when conditions are created (primarily financial), such waste should be exported for destruction in hazardous waste incinerators. Meanwhile, it needs to be assured that any persistent organic pollutants management activity does not negatively impact recycling flows or disturb progress towards a more circular economy in Serbia. © The Author(s) 2016.

Speckle-correlation analysis of the microcapillary blood circulation in nail bed

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vilenskii, M A; Agafonov, D N; Zimnyakov, D A

2011-04-30

We present the results of the experimental studies of the possibility of monitoring the blood microcirculation in human finger nail bed with application of speckle-correlation analysis, based on estimating the contrast of time-averaged dynamic speckles. The hemodynamics at normal blood circulation and under conditions of partially suppressed blood circulation is analysed. A microscopic analysis is performed to visualise the structural changes in capillaries that are caused by suppressing blood circulation. The problems and prospects of speckle-correlation monitoring of the nail bed microhemodynamics under laboratory and clinical conditions are discussed. (optical technologies in biophysics and medicine)

Converging roads: evidence for an adult hemangioblast.

PubMed

Bailey, Alexis S; Fleming, William H

2003-11-01

Classical studies of the developing embryo first suggested the existence of the hemangioblast, a precursor cell with the potential to differentiate into both blood and blood vessels. Several lines of investigation demonstrated that many of the genes activated during early hematopoietic development are also expressed in the vascular endothelium. Gene-targeting studies using embryonic stem cells have identified Flk-1, SCL, and Runx-1 as important regulatory molecules that specify both hematopoietic and vascular outcomes. Although it was anticipated that the hemangioblast would be present only during the earliest stages of vascular development in the yolk sac, accumulating evidence now indicates that hematopoietic cells with hemangioblast activity persist into adulthood. In the adult, bone marrow-derived, circulating endothelial progenitors contribute to postnatal neovascularization and enhance vascular repair following ischemic injury. Highly purified populations of hematopoietic stem cells from humans and mice can differentiate into both blood cells and vascular tissue at the single cell level. These recent findings suggest that bone marrow-derived hematopoietic stem cells or their progeny may contribute to the maintenance and repair of both the hematopoietic and the vascular systems during adult life.

Current Technologies and Recent Developments for Screening of HPV-Associated Cervical and Oropharyngeal Cancers

PubMed Central

Shah, Sunny S.; Senapati, Satyajyoti; Klacsmann, Flora; Miller, Daniel L.; Johnson, Jeff J.; Chang, Hsueh-Chia; Stack, M. Sharon

2016-01-01

Mucosal infection by the human papillomavirus (HPV) is responsible for a growing number of malignancies, predominantly represented by cervical cancer and oropharyngeal squamous cell carcinoma. Because of the prevalence of the virus, persistence of infection, and long latency period, novel and low-cost methods are needed for effective population level screening and monitoring. We review established methods for screening of cervical and oral cancer as well as commercially-available techniques for detection of HPV DNA. We then describe the ongoing development of microfluidic nucleic acid-based biosensors to evaluate circulating host microRNAs that are produced in response to an oncogenic HPV infection. The goal is to develop an ideal screening platform that is low-cost, portable, and easy to use, with appropriate signal stability, sensitivity and specificity. Advances in technologies for sample lysis, pre-treatment and concentration, and multiplexed nucleic acid detection are provided. Continued development of these devices provides opportunities for cancer screening in low resource settings, for point-of-care diagnostics and self-screening, and for monitoring response to vaccination or surgical treatment. PMID:27618102

Long-term isolation and local adaptation in Palau's Nikko Bay help corals thrive in acidic waters

NASA Astrophysics Data System (ADS)

Golbuu, Yimnang; Gouezo, Marine; Kurihara, Haruko; Rehm, Lincoln; Wolanski, Eric

2016-09-01

The reefs in Palau's Nikko Bay live in seawater with low pH that is similar to conditions predicted for 2100 because of ocean acidification. Nevertheless, the reefs at Nikko Bay have high coral cover and high diversity. We hypothesize that the low-pH environment in Nikko Bay is caused by low flushing rates, which causes long-term isolation and local adaptation. To test this hypothesis, we modeled the water circulation in and around Nikko Bay. Model results show that average residence time is 71 d, which is ten times the residence time on fore-reef habitats. The long residence time restricts the exchange of coral larvae in the bay with adjacent reefs, allowing persistent selection for tolerant traits and local adaptation. The corals in Nikko Bay are also more susceptible to local pollution because the waters are poorly flushed. Therefore, local management must focus on minimizing human impacts such as dredging, overfishing and pollution in the bay, which would compromise the condition of the corals that have already adapted to low-pH conditions.

Complex neurological symptoms in bilateral thalamic stroke due to Percheron artery occlusion.

PubMed

Caruso, Paola; Manganotti, Paolo; Moretti, Rita

2017-01-01

The artery of Percheron is a rare anatomical variant where a single thalamic perforating artery arises from the proximal posterior cerebral artery (P1 segment) between the basilar artery and the posterior communicating artery and supplies the rostral mesencephalon and both paramedian territories of the thalami. Almost one-third of human brains present this variant. Occlusion of the artery of Percheron mostly results in a bilateral medial thalamic infarction, which usually manifests with altered consciousness (including coma), vertical gaze paresis, and cognitive disturbance. The presentation is similar to the "top of the basilar syndrome", and early recognition should be prompted. We describe the case of a young female with this vessel variant who experienced a bilateral thalamic stroke. Magnetic resonance angiography demonstrated bilateral thalamic infarcts and a truncated artery of Percheron. Occlusion of the vessel was presumably due to embolism from a patent foramen ovale. Thrombolysis was performed, with incomplete symptom remission, cognitive impairment, and persistence of speech disorders. Early recognition and treatment of posterior circulation strokes is mandatory, and further investigation for underlying stroke etiologies is needed.

Computational prediction of human salivary proteins from blood circulation and application to diagnostic biomarker identification.

PubMed

Wang, Jiaxin; Liang, Yanchun; Wang, Yan; Cui, Juan; Liu, Ming; Du, Wei; Xu, Ying

2013-01-01

Proteins can move from blood circulation into salivary glands through active transportation, passive diffusion or ultrafiltration, some of which are then released into saliva and hence can potentially serve as biomarkers for diseases if accurately identified. We present a novel computational method for predicting salivary proteins that come from circulation. The basis for the prediction is a set of physiochemical and sequence features we found to be discerning between human proteins known to be movable from circulation to saliva and proteins deemed to be not in saliva. A classifier was trained based on these features using a support-vector machine to predict protein secretion into saliva. The classifier achieved 88.56% average recall and 90.76% average precision in 10-fold cross-validation on the training data, indicating that the selected features are informative. Considering the possibility that our negative training data may not be highly reliable (i.e., proteins predicted to be not in saliva), we have also trained a ranking method, aiming to rank the known salivary proteins from circulation as the highest among the proteins in the general background, based on the same features. This prediction capability can be used to predict potential biomarker proteins for specific human diseases when coupled with the information of differentially expressed proteins in diseased versus healthy control tissues and a prediction capability for blood-secretory proteins. Using such integrated information, we predicted 31 candidate biomarker proteins in saliva for breast cancer.

Computational Prediction of Human Salivary Proteins from Blood Circulation and Application to Diagnostic Biomarker Identification

PubMed Central

Wang, Jiaxin; Liang, Yanchun; Wang, Yan; Cui, Juan; Liu, Ming; Du, Wei; Xu, Ying

2013-01-01

Proteins can move from blood circulation into salivary glands through active transportation, passive diffusion or ultrafiltration, some of which are then released into saliva and hence can potentially serve as biomarkers for diseases if accurately identified. We present a novel computational method for predicting salivary proteins that come from circulation. The basis for the prediction is a set of physiochemical and sequence features we found to be discerning between human proteins known to be movable from circulation to saliva and proteins deemed to be not in saliva. A classifier was trained based on these features using a support-vector machine to predict protein secretion into saliva. The classifier achieved 88.56% average recall and 90.76% average precision in 10-fold cross-validation on the training data, indicating that the selected features are informative. Considering the possibility that our negative training data may not be highly reliable (i.e., proteins predicted to be not in saliva), we have also trained a ranking method, aiming to rank the known salivary proteins from circulation as the highest among the proteins in the general background, based on the same features. This prediction capability can be used to predict potential biomarker proteins for specific human diseases when coupled with the information of differentially expressed proteins in diseased versus healthy control tissues and a prediction capability for blood-secretory proteins. Using such integrated information, we predicted 31 candidate biomarker proteins in saliva for breast cancer. PMID:24324552

Hydroxylated polychlorinated biphenyls decrease circulating steroids in female polar bears (Ursus maritimus).

PubMed

Gustavson, Lisa; Ciesielski, Tomasz M; Bytingsvik, Jenny; Styrishave, Bjarne; Hansen, Martin; Lie, Elisabeth; Aars, Jon; Jenssen, Bjørn M

2015-04-01

As a top predator in the Arctic food chain, polar bears (Ursus maritimus) are exposed to high levels of persistent organic pollutants (POPs). Because several of these compounds have been reported to alter endocrine pathways, such as the steroidogenesis, potential disruption of the sex steroid synthesis by POPs may cause implications for reproduction by interfering with ovulation, implantation and fertility. Blood samples were collected from 15 female polar bears in Svalbard (Norway) in April 2008. The concentrations of nine circulating steroid hormones; dehydroepiandrosterone (DHEA), androstenedione (AN), testosterone (TS), dihydrotestosterone (DHT), estrone (E1), 17α-estradiol (αE2), 17β-estradiol (βE2), pregnenolone (PRE) and progesterone (PRO) were determined. The aim of the study was to investigate associations among circulating levels of specific POP compounds and POP-metabolites (hydroxylated PCBs [OH-PCBs] and hydroxylated PBDEs [OH-PBDEs]), steroid hormones, biological and capture variables in female polar bears. Inverse correlations were found between circulating levels of PRE and AN, and circulating levels of OH-PCBs. There were no significant relationships between the steroid concentrations and other analyzed POPs or the variables capture date and capture location (latitude and longitude), lipid content, condition and body mass. Although statistical associations do not necessarily represent direct cause-effect relationships, the present study indicate that OH-PCBs may affect the circulating levels of AN and PRE in female polar bears and that OH-PCBs thus may interfere with the steroid homeostasis. Increase in PRO and a decrease in AN concentrations suggest that the enzyme CYP17 may be a potential target for OH-PCBs. In combination with natural stressors, ongoing climate change and contaminant exposure, it is possible that OH-PCBs may disturb the reproductive potential of polar bears. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of acute exposure to coarse particulate matter air pollution in a rural location on circulating endothelial progenitor cells: results from a randomized controlled study

PubMed Central

Brook, Robert D.; Bard, Robert L.; Kaplan, Mariana J.; Yalavarthi, Srilakshmi; Morishita, Masako; Dvonch, J. Timothy; Wang, Lu; Yang, Hui-yu; Spino, Catherine; Mukherjee, Bhramar; Oral, Elif A.; Sun, Qinghua; Brook, Jeffrey R.; Harkema, Jack; Rajagopalan, Sanjay

2015-01-01

Context Fine particulate matter (PM) air pollution has been associated with alterations in circulating endothelial progenitor cell (EPC) levels, which may be one mechanism whereby exposures promote cardiovascular diseases. However, the impact of coarse PM on EPCs is unknown. Objective We aimed to determine the effect of acute exposure to coarse concentrated ambient particles (CAP) on circulating EPC levels. Methods Thirty-two adults (25.9±6.6 years) were exposed to coarse CAP (76.2±51.5 μgm−3) in a rural location and filtered air (FA) for 2 h in a randomized double-blind crossover study. Peripheral venous blood was collected 2 and 20 h post-exposures for circulating EPC (n=21), white blood cell (n=24) and vascular endothelial growth factor (VEGF) (n=16–19) levels. The changes between exposures were compared by matched Wilcoxon signed-rank tests. Results Circulating EPC levels were elevated 2 [108.29 (6.24–249.71) EPC mL−1; median (25th–75th percentiles), p=0.052] and 20 h [106.86 (52.91–278.35) EPC mL−1, p=0.008] post-CAP exposure compared to the same time points following FA [38.47 (0.00–84.83) and 50.16 (0.00–104.79) EPC mL−1]. VEGF and white blood cell (WBC) levels did not differ between exposures. Conclusions Brief inhalation of coarse PM from a rural location elicited an increase in EPCs that persisted for at least 20 h. The underlying mechanism responsible may reflect a systemic reaction to an acute “endothelial injury” and/or a circulating EPC response to sympathetic nervous system activation. PMID:23919441

Circulating Magnetic Microbubbles for Localized Real-Time Control of Drug Delivery by Ultrasonography-Guided Magnetic Targeting and Ultrasound

PubMed Central

Chertok, Beata; Langer, Robert

2018-01-01

Image-guided and target-selective modulation of drug delivery by external physical triggers at the site of pathology has the potential to enable tailored control of drug targeting. Magnetic microbubbles that are responsive to magnetic and acoustic modulation and visible to ultrasonography have been proposed as a means to realize this drug targeting strategy. To comply with this strategy in vivo, magnetic microbubbles must circulate systemically and evade deposition in pulmonary capillaries, while also preserving magnetic and acoustic activities in circulation over time. Unfortunately, challenges in fabricating magnetic microbubbles with such characteristics have limited progress in this field. In this report, we develop magnetic microbubbles (MagMB) that display strong magnetic and acoustic activities, while also preserving the ability to circulate systemically and evade pulmonary entrapment. Methods: We systematically evaluated the characteristics of MagMB including their pharmacokinetics, biodistribution, visibility to ultrasonography and amenability to magneto-acoustic modulation in tumor-bearing mice. We further assessed the applicability of MagMB for ultrasonography-guided control of drug targeting. Results: Following intravenous injection, MagMB exhibited a 17- to 90-fold lower pulmonary entrapment compared to previously reported magnetic microbubbles and mimicked circulation persistence of the clinically utilized Definity microbubbles (>10 min). In addition, MagMB could be accumulated in tumor vasculature by magnetic targeting, monitored by ultrasonography and collapsed by focused ultrasound on demand to activate drug deposition at the target. Furthermore, drug delivery to target tumors could be enhanced by adjusting the magneto-acoustic modulation based on ultrasonographic monitoring of MagMB in real-time. Conclusions: Circulating MagMB in conjunction with ultrasonography-guided magneto-acoustic modulation may provide a strategy for tailored minimally-invasive control over drug delivery to target tissues. PMID:29290812

[Entomologic situation regarding arbovirus circulation in the Guajaibon area].

PubMed

Fuentes González, O; Fernández Martínez, A; Castex Rodríguez, M; Pelegrino Martínez, J L

1989-01-01

The collections of culicidae made in the Guajaibón area, North coast of Havana province, are analyzed with arbovirologic purposes. The predominance of Aedes scapularis in the human bait collections is confirmed. The possibility of arbovirus circulation in the area is suggested.

Parasitological Confirmation and Analysis of Leishmania Diversity in Asymptomatic and Subclinical Infection following Resolution of Cutaneous Leishmaniasis.

PubMed

Rosales-Chilama, Mariana; Gongora, Rafael E; Valderrama, Liliana; Jojoa, Jimena; Alexander, Neal; Rubiano, Luisa C; Cossio, Alexandra; Adams, Emily R; Saravia, Nancy G; Gomez, María Adelaida

2015-12-01

The contribution of individuals with subclinical infection to the transmission and endemicity of cutaneous leishmaniasis (CL) is unknown. Immunological evidence of exposure to Leishmania in residents of endemic areas has been the basis for defining the human population with asymptomatic infection. However, parasitological confirmation of subclinical infection is lacking. We investigated the presence and viability of Leishmania in blood and non-invasive mucosal tissue samples from individuals with immunological evidence of subclinical infection in endemic areas for CL caused by Leishmania (Viannia) in Colombia. Detection of Leishmania kDNA was conducted by PCR-Southern Blot, and parasite viability was confirmed by amplification of parasite 7SLRNA gene transcripts. A molecular tool for genetic diversity analysis of parasite populations causing persistent subclinical infection based on PCR amplification and sequence analysis of an 82bp region between kDNA conserved blocks 1 and 2 was developed. Persistent Leishmania infection was demonstrated in 40% (46 of 114) of leishmanin skin test (LST) positive individuals without active disease; parasite viability was established in 59% of these (27 of 46; 24% of total). Parasite burden quantified from circulating blood monocytes, nasal, conjunctival or tonsil mucosal swab samples was comparable, and ranged between 0.2 to 22 parasites per reaction. kDNA sequences were obtained from samples from 2 individuals with asymptomatic infection and from 26 with history of CL, allowing genetic distance analysis that revealed diversity among sequences and clustering within the L. (Viannia) subgenus. Our results provide parasitological confirmation of persistent infection among residents of endemic areas of L. (Viannia) transmission who have experienced asymptomatic infection or recovered from CL, revealing a reservoir of infection that potentially contributes to the endemicity and transmission of disease. kDNA genotyping establishes proof-of-principle of the feasibility of genetic diversity analysis in previously inaccessible and unexplored parasite populations in subclinically infected individuals.

Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells

DTIC Science & Technology

2015-10-01

xenograft models . 12-36 Dr. Engelman Subtask 3: Analyze CTCs for P-4EBP1, P-S6, BIM , Bcl-2, Bcl-xL, and Mcl-1 using ISH and IHC We propose...Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells PRINCIPAL INVESTIGATOR: Jeffrey Engelman MD PhD CONTRACTING...reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions

Physiological, Pharmacological, and Nutritional Regulation of Circulating Adiponectin Concentrations in Humans

PubMed Central

Swarbrick, Michael M.

2008-01-01

Abstract Adiponectin is an adipocyte hormone that links visceral adiposity with insulin resistance and atherosclerosis. It is unique among adipocyte-derived hormones in that its circulating concentrations are inversely proportional to adiposity, and low adiponectin concentrations predict the development of type 2 diabetes and cardiovascular disease. Consequently, in the decade since its discovery, adiponectin has generated immense interest as a potential therapeutic target for the metabolic syndrome and diabetes. This review summarizes current research regarding the regulation of circulating adiponectin concentrations by physiological, pharmacological, and nutritional factors, with an emphasis on human studies. In humans, plasma adiponectin concentrations are influenced by age and gender, and are inversely proportional to visceral adiposity. In vitro studies suggest that adiponectin production may be determined primarily by adipocyte size and insulin sensitivity, with larger, insulin-resistant adipocytes producing less adiponectin. While adiponectin concentrations are unchanged after meal ingestion, they are increased by significant weight loss, such as after bariatric surgery. In addition, adiponectin production is inhibited by a number of hormones, including testosterone, prolactin, glucocorticoids and growth hormone, and by inflammation and oxidative stress in adipose tissue. Smoking decreases, while moderate alcohol consumption increases, circulating adiponectin concentrations. Dietary fatty acid composition in rodents influences adiponectin production via ligand-activated nuclear receptors (PPARs); however, current evidence in humans is equivocal. In addition to PPAR agonists (such as thiazolidinediones and fibrates), a number of pharmacological agents (angiotensin receptor type 1 blockers, ACE inhibitors, and cannabinoid receptor antagonists) used in treatment of the metabolic syndrome also increase adiponectin concentrations in humans. PMID:18510434

Atmospheric Circulation Anomalies During Two Persistent North American Droughts: 1932-1939 and 1948-1957

NASA Technical Reports Server (NTRS)

Cook, Benjamin; Seager, Richard; Miller, R. L.

2010-01-01

We use an early twentieth century (1908-1958) atmospheric reanalysis, based on assimilation of surface and sea level pressure observations, to contrast atmospheric circulation during two periods of persistent drought in North America: 1932-1939 (the Dust Bowl) and 1948-1957. Primary forcing for both droughts is believed to come from anomalous sea surface temperatures (SSTs): a warm Atlantic and a cool eastern tropical Pacific. For boreal winter (October-March) in the 1950s, a stationary wave pattern originating from the tropical Pacific is present, with positive centers over the north Pacific and north Atlantic ocean basins and a negative center positioned over northwest North America and the tropical/subtropical Pacific. This wave train is largely absent for the 1930s drought; boreal winter height anomalies are organized much more zonally, with positive heights extending across northern North America. For boreal summer (April-September) during the 1930s, a strong upper level ridge is centered over the Great Plains; this feature is absent during the 1950s and appears to be linked to a weakening of the Great Plains low-level jet (GPLLJ). Subsidence anomalies are co-located over the centers of each drought: in the central Great Plains for the 1930s and in a band extending from the southwest to the southeastern United States for the 1950s. The location and intensity of this subsidence during the 1948-1957 drought is a typical response to a cold eastern tropical Pacific, but for 1932-1939 deviates in terms of the expected intensity, location, and spatial extent. Overall, circulation anomalies during the 1950s drought appear consistent with the expected response to the observed SST forcing. This is not the case for the 1930s, implying some other causal factor may be needed to explain the Dust Bowl drought anomalies. In addition to SST forcing, the 1930s were also characterized by massive alterations to the land surface, including regional-scale devegetation from crop failures and intensive wind erosion and dust storms. Incorporation of these land surface factors into a general circulation model greatly improves the simulation of precipitation and subsidence anomalies during this drought, relative to simulations with SST forcing alone. Even with additional forcing from the land surface, however, the model still has difficulty reproducing some of the other circulation anomalies, including weakening of the GPLLJ and strengthening of the upper level ridge during AMJJAS. This may be due to either weaknesses in the model or uncertainties in the boundary condition estimates. Still, analysis of the circulation anomalies supports the conclusion of an earlier paper (Cook et al. in Proc Natl Acad Sci 106:4997, 2009), demonstrating that land degradation factors are consistent with the anomalous nature of the Dust Bowl drought.

MiRNA-124 is a link between measles virus persistent infection and cell division of human neuroblastoma cells.

PubMed

Naaman, Hila; Rall, Glenn; Matullo, Christine; Veksler-Lublinsky, Isana; Shemer-Avni, Yonat; Gopas, Jacob

2017-01-01

Measles virus (MV) infects a variety of lymphoid and non-lymphoid peripheral organs. However, in rare cases, the virus can persistently infect cells within the central nervous system. Although some of the factors that allow MV to persist are known, the contribution of host cell-encoded microRNAs (miRNA) have not been described. MiRNAs are a class of noncoding RNAs transcribed from genomes of all multicellular organisms and some viruses, which regulate gene expression in a sequence-specific manner. We have studied the contribution of host cell-encoded miRNAs to the establishment of MV persistent infection in human neuroblastoma cells. Persistent MV infection was accompanied by differences in the expression profile and levels of several host cell-encoded microRNAs as compared to uninfected cells. MV persistence infection of a human neuroblastoma cell line (UKF-NB-MV), exhibit high miRNA-124 expression, and reduced expression of cyclin dependent kinase 6 (CDK6), a known target of miRNA-124, resulting in slower cell division but not cell death. By contrast, acute MV infection of UKF-NB cells did not result in increased miRNA-124 levels or CDK6 reduction. Ectopic overexpression of miRNA-124 affected cell viability only in UKF-NB-MV cells, causing cell death; implying that miRNA-124 over expression can sensitize cells to death only in the presence of MV persistent infection. To determine if miRNA-124 directly contributes to the establishment of MV persistence, UKF-NB cells overexpressing miRNA-124 were acutely infected, resulting in establishment of persistently infected colonies. We propose that miRNA-124 triggers a CDK6-dependent decrease in cell proliferation, which facilitates the establishment of MV persistence in neuroblastoma cells. To our knowledge, this is the first report to describe the role of a specific miRNA in MV persistence.

Persistence of highly pathogenic avian influenza H5N1 virus defined by agro-ecological niche

USGS Publications Warehouse

Hogerwerf, Lenny; Wallace, Rob G.; Ottaviani, Daniela; Slingenbergh, Jan; Prosser, Diann; Bergmann, Luc; Gilbert, Marius

2010-01-01

The highly pathogenic avian influenza (HPAI) H5N1 virus has spread across Eurasia and into Africa. Its persistence in a number of countries continues to disrupt poultry production, impairs smallholder livelihoods, and raises the risk a genotype adapted to human-to-human transmission may emerge. While previous studies identified domestic duck reservoirs as a primary risk factor associated with HPAI H5N1 persistence in poultry in Southeast Asia, little is known of such factors in countries with different agro-ecological conditions, and no study has investigated the impact of such conditions on HPAI H5N1 epidemiology at the global scale. This study explores the patterns of HPAI H5N1 persistence worldwide, and for China, Indonesia, and India includes individual provinces that have reported HPAI H5N1 presence during the 2004–2008 period. Multivariate analysis of a set of 14 agricultural, environmental, climatic, and socio-economic factors demonstrates in quantitative terms that a combination of six variables discriminates the areas with human cases and persistence: agricultural population density, duck density, duck by chicken density, chicken density, the product of agricultural population density and chicken output/input ratio, and purchasing power per capita. The analysis identifies five agro-ecological clusters, or niches, representing varying degrees of disease persistence. The agro-ecological distances of all study areas to the medoid of the niche with the greatest number of human cases are used to map HPAI H5N1 risk globally. The results indicate that few countries remain where HPAI H5N1 would likely persist should it be introduced.

AZD2171, a Pan-VEGF Receptor Tyrosine Kinase Inhibitor, Normalizes Tumor Vasculature and Alleviates Edema in Glioblastoma Patients

PubMed Central

Batchelor, Tracy T.; Sorensen, A. Gregory; di Tomaso, Emmanuelle; Zhang, Wei-Ting; Duda, Dan G.; Cohen, Kenneth S.; Kozak, Kevin R.; Cahill, Daniel P.; Chen, Poe-Jou; Zhu, Mingwang; Ancukiewicz, Marek; Mrugala, Maciej M.; Plotkin, Scott; Drappatz, Jan; Louis, David N.; Ivy, Percy; Scadden, David T.; Benner, Thomas; Loeffler, Jay S.; Wen, Patrick Y.; Jain, Rakesh K.

2009-01-01

SUMMARY Using MRI techniques, we show here that normalization of tumor vessels in recurrent glioblastoma patients by daily administration of AZD2171—an oral tyrosine kinase inhibitor of VEGF receptors—has rapid onset, is prolonged but reversible, and has the significant clinical benefit of alleviating edema. Reversal of normalization began by 28 days, though some features persisted for as long as four months. Basic FGF, SDF1α, and viable circulating endothelial cells (CECs) increased when tumors escaped treatment, and circulating progenitor cells (CPCs) increased when tumors progressed after drug interruption. Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor. PMID:17222792

Regional climates in the GISS global circulation model - Synoptic-scale circulation

NASA Technical Reports Server (NTRS)

Hewitson, B.; Crane, R. G.

1992-01-01

A major weakness of current general circulation models (GCMs) is their perceived inability to predict reliably the regional consequences of a global-scale change, and it is these regional-scale predictions that are necessary for studies of human-environmental response. For large areas of the extratropics, the local climate is controlled by the synoptic-scale atmospheric circulation, and it is the purpose of this paper to evaluate the synoptic-scale circulation of the Goddard Institute for Space Studies (GISS) GCM. A methodology for validating the daily synoptic circulation using Principal Component Analysis is described, and the methodology is then applied to the GCM simulation of sea level pressure over the continental United States (excluding Alaska). The analysis demonstrates that the GISS 4 x 5 deg GCM Model II effectively simulates the synoptic-scale atmospheric circulation over the United States. The modes of variance describing the atmospheric circulation of the model are comparable to those found in the observed data, and these modes explain similar amounts of variance in their respective datasets. The temporal behavior of these circulation modes in the synoptic time frame are also comparable.

Persistence and elimination of human norovirus in food and on food contact surfaces: a critical review

USDA-ARS?s Scientific Manuscript database

This critical review addresses the persistence of human norovirus (NoV) in water, shellfish, processed meats, soils and organic wastes; on berries, herbs, vegetables, fruits and salads; and on food contact surfaces. The review focuses on studies using NoV; information from studies involving only su...

PATTERNS OF PERSISTENT GENITAL HUMAN PAPILLOMAVIRUS INFECTION AMONG WOMEN WORLDWIDE: A LITERATURE REVIEW AND META-ANALYSIS

PubMed Central

Rositch, Anne F.; Koshiol, Jill; Hudgens, Michael; Razzaghi, Hilda; Backes, Danielle M.; Pimenta, Jeanne M.; Franco, Eduardo L.; Poole, Charles; Smith, Jennifer S.

2013-01-01

Persistent high-risk human papillomavirus (HR-HPV) infection is the strongest risk factor for high-grade cervical precancer. We performed a systematic review and meta-analysis of HPV persistence patterns worldwide. Medline and ISI Web of Science were searched through January 1, 2010 for articles estimating HPV persistence or duration of detection. Descriptive and meta-regression techniques were used to summarize variability and the influence of study definitions and characteristics on duration and persistence of cervical HPV infections in women. Among 86 studies providing data on over 100,000 women, 73% defined persistence as HPV positivity at a minimum of two time points. Persistence varied notably across studies and was largely mediated by study region and HPV type, with HPV-16, 31, 33 and 52 being most persistent. Weighted median duration of any-HPV detection was 9.8 months. HR-HPV (9.3 months) persisted longer than low-risk HPV (8.4 months), and HPV-16 (12.4 months) persisted longer than HPV-18 (9.8 months). Among populations of HPV positive women with normal cytology, the median duration of any-HPV detection was 11.5 and HR-HPV detection was10.9 months. In conclusion, we estimated that approximately half of HPV infections persist past 6–12 months. Repeat HPV testing at 12 month intervals could identify women at increased risk of high-grade cervical precancer due to persistent HPV infections. PMID:22961444

Spatial heterogeneity in human activities favors the persistence of wolves in agroecosystems.

PubMed

Ahmadi, Mohsen; López-Bao, José Vicente; Kaboli, Mohammad

2014-01-01

As human populations expand, there is increasing demand and pressure for land. Under this scenario, behavioural flexibility and adaptation become important processes leading to the persistence of large carnivores in human-dominated landscapes such as agroecosystems. A growing interest has recently emerged on the outcome of the coexistence between wolves and humans in these systems. It has been suggested that spatial heterogeneity in human activities would be a major environmental factor modulating vulnerability and persistence of this contentious species in agroecosystems. Here, we combined information from 35 den sites detected between 2011 and 2012 in agroecosystems of western Iran (Hamedan province), a set of environmental variables measured at landscape and fine spatial scales, and generalized linear models to identify patterns of den site selection by wolves in a highly-modified agroecosystem. On a landscape level, wolves selected a mixture of rangelands with scattered dry-farms on hillsides (showing a low human use) to locate their dens, avoiding areas with high densities of settlements and primary roads. On a fine spatial scale, wolves primarily excavated dens into the sides of elevated steep-slope hills with availability of water bodies in the vicinity of den sites, and wolves were relegated to dig in places with coarse-soil particles. Our results suggest that vulnerability of wolves in human-dominated landscapes could be compensated by the existence of spatial heterogeneity in human activities. Such heterogeneity would favor wolf persistence in agroecosystems favoring a land sharing model of coexistence between wolves and people.

Spatial Heterogeneity in Human Activities Favors the Persistence of Wolves in Agroecosystems

PubMed Central

Ahmadi, Mohsen; López-Bao, José Vicente; Kaboli, Mohammad

2014-01-01

As human populations expand, there is increasing demand and pressure for land. Under this scenario, behavioural flexibility and adaptation become important processes leading to the persistence of large carnivores in human-dominated landscapes such as agroecosystems. A growing interest has recently emerged on the outcome of the coexistence between wolves and humans in these systems. It has been suggested that spatial heterogeneity in human activities would be a major environmental factor modulating vulnerability and persistence of this contentious species in agroecosystems. Here, we combined information from 35 den sites detected between 2011 and 2012 in agroecosystems of western Iran (Hamedan province), a set of environmental variables measured at landscape and fine spatial scales, and generalized linear models to identify patterns of den site selection by wolves in a highly-modified agroecosystem. On a landscape level, wolves selected a mixture of rangelands with scattered dry-farms on hillsides (showing a low human use) to locate their dens, avoiding areas with high densities of settlements and primary roads. On a fine spatial scale, wolves primarily excavated dens into the sides of elevated steep-slope hills with availability of water bodies in the vicinity of den sites, and wolves were relegated to dig in places with coarse-soil particles. Our results suggest that vulnerability of wolves in human-dominated landscapes could be compensated by the existence of spatial heterogeneity in human activities. Such heterogeneity would favor wolf persistence in agroecosystems favoring a land sharing model of coexistence between wolves and people. PMID:25251567

Resistance to change and resurgence in humans engaging in a computer task.

PubMed

Kuroda, Toshikazu; Cançado, Carlos R X; Podlesnik, Christopher A

2016-04-01

The relation between persistence, as measured by resistance to change, and resurgence has been examined with nonhuman animals but not systematically with humans. The present study examined persistence and resurgence with undergraduate students engaging in a computer task for points exchangeable for money. In Phase 1, a target response was maintained on a multiple variable-interval (VI) 15-s (Rich) VI 60-s (Lean) schedule of reinforcement. In Phase 2, the target response was extinguished while an alternative response was reinforced at equal rates in both schedule components. In Phase 3, the target and the alternative responses were extinguished. In an additional test of persistence (Phase 4), target responding was reestablished as in Phase 1 and then disrupted by access to videos in both schedule components. In Phases 2 and 4, target responding was more persistent in the Rich than in the Lean component. Also, resurgence generally was greater in the Rich than in the Lean component in Phase 3. The present findings with humans extend the generality of those obtained with nonhuman animals showing that higher reinforcement rates produce both greater persistence and resurgence, and suggest that common processes underlie response persistence and relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

Congruent Strain Specific Intestinal Persistence of Lactobacillus plantarum in an Intestine-Mimicking In Vitro System and in Human Volunteers

PubMed Central

van Bokhorst-van de Veen, Hermien; van Swam, Iris; Wels, Michiel; Bron, Peter A.; Kleerebezem, Michiel

2012-01-01

Background An important trait of probiotics is their capability to reach their intestinal target sites alive to optimally exert their beneficial effects. Assessment of this trait in intestine-mimicking in vitro model systems has revealed differential survival of individual strains of a species. However, data on the in situ persistence characteristics of individual or mixtures of strains of the same species in the gastrointestinal tract of healthy human volunteers have not been reported to date. Methodology/Principal Findings The GI-tract survival of individual L. plantarum strains was determined using an intestine mimicking model system, revealing substantial inter-strain differences. The obtained data were correlated to genomic diversity of the strains using comparative genome hybridization (CGH) datasets, but this approach failed to discover specific genetic loci that explain the observed differences between the strains. Moreover, we developed a next-generation sequencing-based method that targets a variable intergenic region, and employed this method to assess the in vivo GI-tract persistence of different L. plantarum strains when administered in mixtures to healthy human volunteers. Remarkable consistency of the strain-specific persistence curves were observed between individual volunteers, which also correlated significantly with the GI-tract survival predicted on basis of the in vitro assay. Conclusion The survival of individual L. plantarum strains in the GI-tract could not be correlated to the absence or presence of specific genes compared to the reference strain L. plantarum WCFS1. Nevertheless, in vivo persistence analysis in the human GI-tract confirmed the strain-specific persistence, which appeared to be remarkably similar in different healthy volunteers. Moreover, the relative strain-specific persistence in vivo appeared to be accurately and significantly predicted by their relative survival in the intestine-mimicking in vitro assay, supporting the use of this assay for screening of strain-specific GI persistence. PMID:22970257

A cell-based assay to assess the persistence of action of agonists acting at recombinant human beta(2) adrenoceptors.

PubMed

Summerhill, Susan; Stroud, Timothy; Nagendra, Roshini; Perros-Huguet, Christelle; Trevethick, Michael

2008-01-01

The aim was to establish a robust, 96-well, cell-based assay to assess the potency and persistence of action of agonists acting at human recombinant beta(2) adrenoceptors expressed in CHO (Chinese Hamster Ovary) cells and to compare this with published duration of action data in guinea pig isolated trachea and human bronchus. Cells were treated with either: (i) beta-adrenoceptor agonist for 30 min, washed and cyclicAMP (cAMP) measured 30 min later-termed 'washed' cells or, (ii) treated with solvent for 30 min, washed, and then treated with beta-adrenoceptor agonist for 30 min and cAMP measured-termed 'unwashed' cells. The 'washed' EC(50) was divided by the 'unwashed' EC(50) to determine a rightward shift concentration ratio, which was indicative of the persistence of action at the receptor. At the beta(2) adrenoceptor salmeterol, carmoterol and indacaterol were resistant to washing with a concentration ratio of <5, indicating a long persistence of action, whereas formoterol, isoprenaline and salbutamol were washed out with a ratio of 32, >294 and >800 respectively, suggesting a shorter persistence of action. At beta(1) and beta(3) adrenoceptors all compounds washed out. The persistent effects of salmeterol at beta(2) following washing could be reversed by the selective beta(2) antagonist ICI 118551, suggesting continued receptor activation. The data presented agree well with published data assessing duration of action of beta(2) agonists in human isolated bronchus and guinea pig isolated trachea. Key features are: (a) it is a 96-well format which can be used to assess many compounds in a single experiment, (b) both potency and persistence of agonist action are assessed in the same assay, (c) any effects of concentration on the persistence of action can be highlighted, and (d) it allows triage of compounds prior to tissue bath studies thus reducing the use of animal tissue.

Laboratory Surveillance of Rabies in Humans, Domestic Animals, and Bats in Madagascar from 2005 to 2010

PubMed Central

Reynes, Jean-Marc; Andriamandimby, Soa Fy; Razafitrimo, Girard Marcelin; Razainirina, Josette; Jeanmaire, Elisabeth Marie; Bourhy, Hervé; Heraud, Jean-Michel

2011-01-01

Background. Rabies virus (RABV) has circulated in Madagascar at least since the 19th century. Objectives. To assess the circulation of lyssavirus in the island from 2005 to 2010. Materials and Methods. Animal (including bats) and human samples were tested for RABV and other lyssavirus using antigen, ribonucleic acid (RNA), and antibodies detection and virus isolation. Results. Half of the 437 domestic or tame wild terrestrial mammal brains tested were found RABV antigen positive, including 54% of the 341 dogs tested. This percentage ranged from 26% to 75% across the period. Nine of the 10 suspected human cases tested were laboratory confirmed. RABV circulation was confirmed in 34 of the 38 districts sampled. No lyssavirus RNA was detected in 1983 bats specimens. Nevertheless, antibodies against Lagos bat virus were detected in the sera of 12 among 50 Eidolon dupreanum specimens sampled. Conclusion. More than a century after the introduction of the vaccine, rabies still remains endemic in Madagascar. PMID:21991442

Variants of human papillomavirus type 16 predispose toward persistent infection

PubMed Central

Zhang, Lei; Liao, Hong; Yang, Binlie; Geffre, Christopher P; Zhang, Ai; Zhou, Aizhi; Cao, Huimin; Wang, Jieru; Zhang, Zhenbo; Zheng, Wenxin

2015-01-01

A cohort study of 292 Chinese women was conducted to determine the relationship between human papillomavirus (HPV) type 16 variants and persistent viral infection. Enrolled patients were HPV16 positive and had both normal cytology and histology. Flow-through hybridization and gene chip technology was used to identify the HPV type. A PCR sequencing assay was performed to find HPV16 E2, E6 and E7 gene variants. The associations between these variants and HPV16 persistent infection was analyzed by Fisher’s exact test. It was found that the variants T178G, T350G and A442C in the E6 gene, as well as C3158A and G3248A variants in the E2 gene were associated with persistent HPV16 infection. No link was observed between E7 variants and persistent viral infection. Our findings suggest that detection of specific HPV variants would help identify patients who are at high risk for viral persistence and development of cervical neoplasia. PMID:26339417

Regional Stratification and Shear of the Various Streams Feeding the Philippine Straits

DTIC Science & Technology

2009-01-01

Feeding the Philippine Straits Arnold L. Gordon Lamont-Doherty Earth Observatory 61 Route 9W Palisades , NY 10964-8000 tele: 845 365-8325 fax...Observatory,61 Route 9W, Palisades ,NY,10964-8000 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES...The Mindanao Jet flows into the Sulu Sea. To the south of the Mindanao Jet, near 124°E is a persistent cyclonic flowing circulation cell , dubbed the

Persistently Low Natural Killer Cell Activity and Circulating Levels of Plasma Beta Endorphin: Risk Factors for Infectious Disease

DTIC Science & Technology

1990-01-01

influenza, pneumonia, cold sores, gum infections, mononucleosis, strep throat , and gastro-intcstinal illnesses, plus the direct reporting of symptoms such...other upper respiratory symptoms ) over the follow-up period. Specifically, older age predicted lower URI morbidity; younger age was associated with the...work. They were instructed to record daily symptoms of infectious illness experienced, as well as the amount of sleep per night, daily exercise, and

Influence of Antarctic Oscillation on Intraseasonal Variability of Large-Scale Circulations Over the Western North Pacific

DTIC Science & Technology

2005-03-01

quartiles, and thus locates the central 50% of the data. The center bar through each box represents the persistence median. The whiskers extend away from...level of tropical cyclone activity. Numerous factors (e.g., scarcity of observations over large ocean basins , various scales of motion present in the... central South Indian Ocean, South Pacific Ocean east of New Zealand, and South Atlantic Ocean near the Falkland Islands. The increased pressure gradient

Sustained currents in coupled diffusive systems

NASA Astrophysics Data System (ADS)

Larralde, Hernán; Sanders, David P.

2014-08-01

Coupling two diffusive systems may give rise to a nonequilibrium stationary state (NESS) with a non-trivial persistent, circulating current. We study a simple example that is exactly soluble, consisting of random walkers with different biases towards a reflecting boundary, modelling, for example, Brownian particles with different charge states in an electric field. We obtain analytical expressions for the concentrations and currents in the NESS for this model, and exhibit the main features of the system by numerical simulation.

Hydroclimatology of the 2008 Midwest floods

NASA Astrophysics Data System (ADS)

Budikova, D.; Coleman, J. S. M.; Strope, S. A.; Austin, A.

2010-12-01

The late spring/early summer flooding that occurred in the American Midwest between May and June 2008 resulted from a combination of large-scale atmospheric circulation patterns that supported a steady influx of moisture into the area. A low pressure system centered over the central-western United States steered a strong jet and associated storms along its eastern edge from the west to southwest and an anomalously strong Great Plains Low Level Jet brought continuous warm and moist air into the area from the Gulf of Mexico into the area. We examine and quantify here the impact these circulation patterns had on the hydroclimatology of the Midwest highlighting the magnitude, frequency, geographic distribution, and temporal evolution of precipitation that ultimately magnified the flooding. Historical precipitation records were used to assess the regional rainfall characteristics at various geographic and time scales. Five distinct hydroclimatic characteristics contributed to the definition of the 2008 flood including persistent high surface soil moisture conditions prior to flooding exasperated by anomalously high rainfall, extreme rainfall totals covering extensive areas, increased frequency of shorter-term, smaller-magnitude events, persistent multiday heavy precipitation events, and extreme flood-producing rain storms. The major flooding lasted for approximately 24 days and most greatly impacted the state of Iowa, southern Wisconsin, and central Indiana. Its occurrence during the May-June period makes the event especially unusual for this region.

Persistence and spreading of field and vaccine strains of infectious laryngotracheitis virus (ILTV) in vaccinated and unvaccinated geographic regions, in Brazil.

PubMed

Chacón, Jorge Luis; Núñez, Luis Fabian Naranjo; Vejarano, Maria Pilar; Parra, Silvana Hipatia Santander; Astolfi-Ferreira, Claudete Serrano; Ferreira, Antonio José Piantino

2015-08-01

Infectious laryngotracheitis (ILT) is a highly infectious respiratory disease that causes morbidity and mortality in commercial chickens. Despite the use of attenuated vaccines, ILT outbreaks have been described in broiler and long-lived birds. Molecular approaches, including polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing, are used to characterize ILT viruses (ILTVs) detected in vaccinated and unvaccinated geographical regions. As part of an ILT control program implemented in a region of commercial layer production, samples of conjunctiva, trachea, and trigeminal ganglia were collected from chickens in a vaccinated and quarantined region over a period of 8 years after initiation of vaccination. To determine the origin of new ILT outbreaks in unvaccinated regions, samples collected from ill chickens were also analyzed. Chicken embryo origin (CEO) vaccine viruses and the Bastos field strain were detected circulating in healthy chickens in the vaccinated region. CEO strains and field viruses molecularly related to the Bastos strain were also detected outside of the quarantined region in chickens showing clinical signs of ILT. This study reveals the persistence and circulation of a wild field strain, despite the intensive use of tissue culture origin (TCO) and CEO vaccines in a quarantined region. Spreading of CEO viruses to unvaccinated regions and the capacity of this virus to establish latent infections and cause severe outbreaks were also observed.

The impact of boreal autumn SST anomalies over the South Pacific on boreal winter precipitation over East Asia

NASA Astrophysics Data System (ADS)

Ao, Juan; Sun, Jianqi

2016-05-01

The possible mechanism behind the variability in the dipole pattern of boreal winter precipitation over East Asia is analyzed in this study. The results show that the SST anomalies (SSTAs) over the South Pacific Ocean (SPO) in boreal autumn are closely related to the variability in the dipole pattern of boreal winter precipitation over East Asia. The physical link between the boreal autumn SPO SSTAs and the boreal winter East Asian precipitation dipole pattern is shown to mainly be the seasonal persistence of the SPO SSTAs themselves. The seasonal persistence of the SPO SSTAs can memorize and transport the signal of the boreal autumn SSTAs to the following winter, and then stimulates a meridional teleconnection pattern from the SH to the NH, resulting in a meridional dipole pattern of atmospheric circulation over East Asia in boreal winter. As a major influencing factor, this dipole pattern of the atmospheric circulation can finally lead to the anomalous precipitation dipole pattern over East Asia in boreal winter. These observed physical processes are further confirmed in this study through numerical simulation. The evidence from this study, showing the impact of the SPO SSTAs in boreal autumn, not only deepens our understanding of the variability in East Asian boreal winter precipitation, but also provides a potentially useful predictor for precipitation in the region.

Typical meteorological conditions associated with extreme nitrogen dioxide (NO2) pollution events over Scandinavia

NASA Astrophysics Data System (ADS)

Thomas, Manu Anna; Devasthale, Abhay

2017-10-01

Characterizing typical meteorological conditions associated with extreme pollution events helps to better understand the role of local meteorology in governing the transport and distribution of pollutants in the atmosphere. The knowledge of their co-variability could further help to evaluate and constrain chemistry transport models. Hence, in this study, we investigate the statistical linkages between extreme nitrogen dioxide (NO2) pollution events and meteorology over Scandinavia using observational and reanalysis data. It is observed that the south-westerly winds dominated during extreme events, accounting for 50-65 % of the total events depending on the season, while the second largest annual occurrence was from south-easterly winds, accounting for 17 % of total events. The specific humidity anomalies showed an influx of warmer and moisture-laden air masses over Scandinavia in the free troposphere. Two distinct modes in the persistency of circulation patterns are observed. The first mode lasts for 1-2 days, dominated by south-easterly winds that prevailed during 78 % of total extreme events in that mode, while the second mode lasted for 3-5 days, dominated by south-westerly winds that prevailed during 86 % of the events. The combined analysis of circulation patterns, their persistency, and associated changes in humidity and clouds suggests that NO2 extreme events over Scandinavia occur mainly due to long-range transport from the southern latitudes.

Properties of the tick-borne encephalitis virus population during persistent infection of ixodid ticks and tick cell lines.

PubMed

Belova, Oxana A; Litov, Alexander G; Kholodilov, Ivan S; Kozlovskaya, Liubov I; Bell-Sakyi, Lesley; Romanova, Lidiya Iu; Karganova, Galina G

2017-10-01

Tick-borne encephalitis virus (TBEV) is the causative agent of tick-borne encephalitis (TBE), a vector-borne zoonotic neuroinfection. For successful circulation in natural foci the virus has to survive in the vector for a long period of time. Information about the effect of long-term infection of ticks on properties of the viral population is of great importance. In recent years, changes in the eco-epidemiology of TBEV due to changes in distribution of ixodid ticks have been observed. These changes in TBEV-endemic areas could result in a shift of the main tick vector species, which in turn may lead to changes in properties of the virus. In the present study we evaluated the selective pressure on the TBEV population during persistent infection of various species of ticks and tick cell lines. TBEV effectively replicated and formed persistent infection in ticks and tick cell lines of the vector species (Ixodes spp.), potential vectors (Dermacentor spp.) and non-vector ticks (Hyalomma spp.). During TBEV persistence in Ixodes and Dermacentor ticks, properties of the viral population remained virtually unchanged. In contrast, persistent TBEV infection of tick cell lines from both vector and non-vector ticks favoured selection of viral variants with low neuroinvasiveness for laboratory mice and substitutions in the E protein that increased local positive charge of the virion. Thus, selective pressure on viral population may differ in ticks and tick cell lines during persistent infection. Nevertheless, virus variants with properties of the original strain adapted to mouse CNS were not eliminated from the viral population during long-term persistence of TBEV in ticks and tick cell lines. Copyright © 2017 Elsevier GmbH. All rights reserved.

Human Babesiosis in Japan: Isolation of Babesia microti-Like Parasites from an Asymptomatic Transfusion Donor and from a Rodent from an Area Where Babesiosis Is Endemic

PubMed Central

Wei, Qiang; Tsuji, Masayoshi; Zamoto, Aya; Kohsaki, Masatoshi; Matsui, Toshimitsu; Shiota, Tsunezo; Telford, Sam R.; Ishihara, Chiaki

2001-01-01

To determine the source of infection for the Japanese index case of human babesiosis, we analyzed blood samples from an asymptomatic individual whose blood had been transfused into the patient. In addition, we surveyed rodents collected from near the donor's residence. Examination by microscopy and PCR failed to detect the parasite in the donor's blood obtained 8 months after the donation of the blood that was transfused. However, we were able to isolate Babesia parasites by inoculating the blood sample into SCID mice whose circulating red blood cells (RBCs) had been replaced with human RBCs. A Babesia parasite capable of propagating in human RBCs was also isolated from a field mouse (Apodemus speciosus) captured near the donor's residential area. Follow-up surveys over a 1-year period revealed that the donor continued to be asymptomatic but had consistently high immunoglobulin G (IgG) titers in serum and low levels of parasitemia which were microscopically undetectable yet which were repeatedly demonstrable by inoculation into animals. The index case patient's sera contained high titers of IgM and, subsequently, rising titers of IgG antibodies, both of which gradually diminished with the disappearance of the parasitemia. Analysis of the parasite's rRNA gene (rDNA) sequence and immunodominant antigens revealed the similarity between donor and patient isolates. The rodent isolate also had an rDNA sequence that was identical to that of the human isolates but that differed slightly from that of the human isolates by Western blot analysis. We conclude that the index case patient acquired infection by transfusion from a donor who became infected in Japan, that parasitemia in an asymptomatic carrier can persist for more than a year, and that A. speciosus serves as a reservoir of an agent of human babesiosis in Japan. PMID:11376054

Comparison of the first three waves of avian influenza A(H7N9) virus circulation in the mainland of the People's Republic of China.

PubMed

Xiang, Nijuan; Iuliano, A Danielle; Zhang, Yanping; Ren, Ruiqi; Geng, Xingyi; Ye, Bili; Tu, Wenxiao; Li, Ch Ao; Lv, Yong; Yang, Ming; Zhao, Jian; Wang, Yali; Yang, Fuqiang; Zhou, Lei; Liu, Bo; Shu, Yuelong; Ni, Daxin; Feng, Zijian; Li, Qun

2016-12-05

H7N9 human cases were first detected in mainland China in March 2013. Circulation of this virus has continued each year shifting to typical winter months. We compared the clinical and epidemiologic characteristics for the first three waves of virus circulation. The first wave was defined as reported cases with onset dates between March 31-September 30, 2013, the second wave was defined as October 1, 2013-September 30, 2014 and the third wave was defined as October 1, 2014-September 30, 2015. We used simple descriptive statistics to compare characteristics of the three distinct waves of virus circulation. In mainland China, 134 cases, 306 cases and 219 cases were detected and reported in first three waves, respectively. The median age of cases was statistically significantly older in the first wave (61 years vs. 56 years, 56 years, p < 0.001) compared to the following two waves. Most reported cases were among men in all three waves. There was no statistically significant difference between case fatality proportions (33, 42 and 45%, respectively, p = 0.08). There were no significant statistical differences for time from illness onset to first seeking healthcare, hospitalization, lab confirmation, initiation antiviral treatment and death between the three waves. A similar percentage of cases in all waves reported exposure to poultry or live poultry markets (87%, 88%, 90%, respectively). There was no statistically significant difference in the occurrence of severe disease between the each of the first three waves of virus circulation. Twenty-one clusters were reported during these three waves (4, 11 and 6 clusters, respectively), of which, 14 were considered to be possible human-to-human transmission. Though our case investigation for the first three waves found few differences between the epidemiologic and clinical characteristics, there is continued international concern about the pandemic potential of this virus. Since the virus continues to circulate, causes more severe disease, has the ability to mutate and become transmissible from human-to-human, and there is limited natural protection from infection in communities, it is critical that surveillance systems in China and elsewhere are alert to the influenza H7N9 virus.

Summer monsoon circulation and precipitation over the tropical Indian Ocean during ENSO in the NCEP climate forecast system

NASA Astrophysics Data System (ADS)

Chowdary, J. S.; Chaudhari, H. S.; Gnanaseelan, C.; Parekh, Anant; Suryachandra Rao, A.; Sreenivas, P.; Pokhrel, S.; Singh, P.

2014-04-01

This study investigates the El Niño Southern Oscillation (ENSO) teleconnections to tropical Indian Ocean (TIO) and their relationship with the Indian summer monsoon in the coupled general circulation model climate forecast system (CFS). The model shows good skill in simulating the impact of El Niño over the Indian Oceanic rim during its decay phase (the summer following peak phase of El Niño). Summer surface circulation patterns during the developing phase of El Niño are more influenced by local Sea Surface Temperature (SST) anomalies in the model unlike in observations. Eastern TIO cooling similar to that of Indian Ocean Dipole (IOD) is a dominant model feature in summer. This anomalous SST pattern therefore is attributed to the tendency of the model to simulate more frequent IOD events. On the other hand, in the model baroclinic response to the diabatic heating anomalies induced by the El Niño related warm SSTs is weak, resulting in reduced zonal extension of the Rossby wave response. This is mostly due to weak eastern Pacific summer time SST anomalies in the model during the developing phase of El Niño as compared to observations. Both eastern TIO cooling and weak SST warming in El Niño region combined together undermine the ENSO teleconnections to the TIO and south Asia regions. The model is able to capture the spatial patterns of SST, circulation and precipitation well during the decay phase of El Niño over the Indo-western Pacific including the typical spring asymmetric mode and summer basin-wide warming in TIO. The model simulated El Niño decay one or two seasons later, resulting long persistent warm SST and circulation anomalies mainly over the southwest TIO. In response to the late decay of El Niño, Ekman pumping shows two maxima over the southern TIO. In conjunction with this unrealistic Ekman pumping, westward propagating Rossby waves display two peaks, which play key role in the long-persistence of the TIO warming in the model (for more than a season after summer). This study strongly supports the need of simulating the correct onset and decay phases of El Niño/La Niña for capturing the realistic ENSO teleconnections. These results have strong implications for the forecasting of Indian summer monsoon as this model is currently being adopted as an operational model in India.

[Yellow fever: reemerging in the state of Sao Paulo, Brazil, 2009].

PubMed

Mascheretti, Melissa; Tengan, Ciléa H; Sato, Helena Keiko; Suzuki, Akemi; de Souza, Renato Pereira; Maeda, Marina; Brasil, Roosecelis; Pereira, Mariza; Tubaki, Rosa Maria; Wanderley, Dalva M V; Fortaleza, Carlos Magno Castelo Branco; Ribeiro, Ana Freitas

2013-10-01

To describe the investigation of a sylvatic yellow fever outbreak in the state of Sao Paulo and the main control measures undertaken. This is a descriptive study of a sylvatic yellow fever outbreak in the Southwestern region of the state from February to April 2009. Suspected and confirmed cases in humans and in non-human primates were evaluated. Entomological investigation in sylvatic environment involved capture at ground level and in the tree canopy to identify species and detect natural infections. Control measures were performed in urban areas to control Aedes aegypti . Vaccination was directed at residents living in areas with confirmed viral circulation and also at nearby cities according to national recommendation. Twenty-eight human cases were confirmed (39.3% case fatality rate) in rural areas of Sarutaiá, Piraju, Tejupá, Avaré and Buri. The deaths of 56 non-human primates were also reported, 91.4% were Allouatta sp. Epizootics was confirmed in two non-human primates in the cities of Itapetininga and Buri. A total of 1,782 mosquitoes were collected, including Haemagogus leucocelaenus , Hg. janthinomys/capricornii , and Sabethes chloropterus, Sa. purpureus and Sa. undosus . Yellow fever virus was isolated from a group of Hg. Leucocelaenus from Buri. Vaccination was carried out in 49 cities, with a total of 1,018,705 doses. Nine serious post-vaccination adverse events were reported. The cases occurred between February and April 2009 in areas with no recorded yellow fever virus circulation in over 60 years. The outbreak region occurred outside the original recommended vaccination area with a high percentage of susceptible population. The fast adoption of control measures interrupted the human transmission within a month and the confirmation of viral circulation in humans, monkeys and mosquitoes. The results allowed the identification of new areas of viral circulation but further studies are required to clarify the dynamics of the spread of this disease.

Dirty Money: A Matter of Bacterial Survival, Adherence, and Toxicity.

PubMed

Vriesekoop, Frank; Chen, Jing; Oldaker, Jenna; Besnard, Flavien; Smith, Reece; Leversha, William; Smith-Arnold, Cheralee; Worrall, Julie; Rufray, Emily; Yuan, Qipeng; Liang, Hao; Scannell, Amalia; Russell, Cryn

2016-11-23

In this study we report the underlying reasons to why bacteria are present on banknotes and coins. Despite the use of credit cards, mobile phone apps, near-field-communication systems, and cryptocurrencies such as bitcoins which are replacing the use of hard currencies, cash exchanges still make up a significant means of exchange for a wide range of purchases. The literature is awash with data that highlights that both coins and banknotes are frequently identified as fomites for a wide range of microorganisms. However, most of these publications fail to provide any insight into the extent to which bacteria adhere and persist on money. We treated the various currencies used in this study as microcosms, and the bacterial loading from human hands as the corresponding microbiome. We show that the substrate from which banknotes are produced have a significant influence on both the survival and adherence of bacteria to banknotes. Smooth, polymer surfaces provide a poor means of adherence and survival, while coarser and more fibrous surfaces provide strong bacterial adherence and an environment to survive on. Coins were found to be strongly inhibitory to bacteria with a relatively rapid decline in survival on almost all coin surfaces tested. The inhibitory influence of coins was demonstrated through the use of antimicrobial disks made from coins. Despite the toxic effects of coins on many bacteria, bacteria do have the ability to adapt to the presence of coins in their environment which goes some way to explain the persistent presence of low levels of bacteria on coins in circulation.

Exploring reservoir dynamics: a case study of rabies in the Serengeti ecosystem

PubMed Central

Lembo, Tiziana; Hampson, Katie; Haydon, Daniel T.; Craft, Meggan; Dobson, Andy; Dushoff, Jonathan; Ernest, Eblate; Hoare, Richard; Kaare, Magai; Mlengeya, Titus; Mentzel, Christine; Cleaveland, Sarah

2012-01-01

Summary Knowledge of infection reservoir dynamics is critical for effective disease control, but identifying reservoirs of multi-host pathogens is challenging. Here, we synthesize several lines of evidence to investigate rabies reservoirs in complex carnivore communities of the Serengeti ecological region in northwest Tanzania, where the disease has been confirmed in 12 carnivore species.Long-term monitoring data suggest that rabies persists in high-density domestic dog Canis familiaris populations (> 11 dogs km−2) and occurs less frequently in lower-density (< 5 dogs km−2) populations and only sporadically in wild carnivores.Genetic data show that a single rabies virus variant belonging to the group of southern Africa canid-associated viruses (Africa 1b) circulates among a range of species, with no evidence of species-specific virus–host associations.Within-species transmission was more frequently inferred from high-resolution epidemiological data than between-species transmission. Incidence patterns indicate that spill-over of rabies from domestic dog populations sometimes initiates short-lived chains of transmission in other carnivores.Synthesis and applications. The balance of evidence suggests that the reservoir of rabies in the Serengeti ecosystem is a complex multi-host community where domestic dogs are the only population essential for persistence, although other carnivores contribute to the reservoir as non-maintenance populations. Control programmes that target domestic dog populations should therefore have the greatest impact on reducing the risk of infection in all other species including humans, livestock and endangered wildlife populations, but transmission in other species may increase the level of vaccination coverage in domestic dog populations necessary to eliminate rabies. PMID:22427710

Dirty Money: A Matter of Bacterial Survival, Adherence, and Toxicity

PubMed Central

Vriesekoop, Frank; Chen, Jing; Oldaker, Jenna; Besnard, Flavien; Smith, Reece; Leversha, William; Smith-Arnold, Cheralee; Worrall, Julie; Rufray, Emily; Yuan, Qipeng; Liang, Hao; Scannell, Amalia; Russell, Cryn

2016-01-01

In this study we report the underlying reasons to why bacteria are present on banknotes and coins. Despite the use of credit cards, mobile phone apps, near-field-communication systems, and cryptocurrencies such as bitcoins which are replacing the use of hard currencies, cash exchanges still make up a significant means of exchange for a wide range of purchases. The literature is awash with data that highlights that both coins and banknotes are frequently identified as fomites for a wide range of microorganisms. However, most of these publications fail to provide any insight into the extent to which bacteria adhere and persist on money. We treated the various currencies used in this study as microcosms, and the bacterial loading from human hands as the corresponding microbiome. We show that the substrate from which banknotes are produced have a significant influence on both the survival and adherence of bacteria to banknotes. Smooth, polymer surfaces provide a poor means of adherence and survival, while coarser and more fibrous surfaces provide strong bacterial adherence and an environment to survive on. Coins were found to be strongly inhibitory to bacteria with a relatively rapid decline in survival on almost all coin surfaces tested. The inhibitory influence of coins was demonstrated through the use of antimicrobial disks made from coins. Despite the toxic effects of coins on many bacteria, bacteria do have the ability to adapt to the presence of coins in their environment which goes some way to explain the persistent presence of low levels of bacteria on coins in circulation. PMID:27886085

21 CFR 868.5250 - Breathing circuit circulator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Breathing circuit circulator. 868.5250 Section 868.5250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... valves in an open position and reducing mechanical dead space and resistance in the breathing circuit. (b...

21 CFR 868.5250 - Breathing circuit circulator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Breathing circuit circulator. 868.5250 Section 868.5250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... valves in an open position and reducing mechanical dead space and resistance in the breathing circuit. (b...

The potential of air-sea interactions for improving summertime North Atlantic seasonal forecasts

NASA Astrophysics Data System (ADS)

Ossó, Albert; Shaffrey, Len; Dong, Buwen; Sutton, Rowan

2017-04-01

Delivering skillful summertime seasonal forecasts of the Northern Hemisphere (NH) mid-latitude climate is a key unresolved issue for the climate science community. Current climate models have some skill in forecasting the wintertime NH mid-latitude circulation but very limited skill during summertime. To explore the potential predictability of the summertime climate we analyze lagged correlation patterns between the SSTs and summer atmospheric circulation in the North Atlantic both in observations and climate model outputs. We find observational evidence in the ERA-Interim (1979-2015) reanalysis and the HadSLP2 and HadISST data of an SST pattern forced by late winter atmospheric circulation persisting from winter to early summer that excites an anticyclonic summer SLP anomaly west of the British Isles. We show that the atmospheric response is driven through the action of turbulent heat fluxes and changes on the background baroclinicity. The lagged atmospheric response to the SSTs could be exploited for summertime predictability over Western Europe. We find a statistical significant correlation of over 0.6 between April-May North Atlantic SSTs and the June-August North Atlantic SLP anomaly. The previous findings are further explored using 120 years of coupled ocean-atmosphere HadGEM3-GC2 model simulation. The climate model qualitatively reproduces the observed spatial relationship between the late winter and spring SSTs and summertime circulation, although the correlations are substantially weaker than observed.

Persistent in vivo cytogenetic effects of radioiodine therapy: a 21-year follow-up study using multicolor FISH.

PubMed

Livingston, Gordon K; Escalona, Maria; Foster, Alvis; Balajee, Adayabalam S

2018-01-01

Our previous studies demonstrated the cytogenetic effects in the peripheral blood lymphocytes of a 34-year-old male patient who received ablative radioactive 131iodine therapy (RIT) on two different occasions in 1992 and 1994. Assessment of RIT-induced chromosomal damage by the cytokinesis-blocked micronucleus assay (CBMN) showed the persistence of elevated micronucleus frequency in this patient for more than two decades since the first RIT. Subsequent cytogenetic analysis performed in 2012 revealed both stable and unstable aberrations, whose frequencies were higher than the baseline reported in the literature. Here, we report the findings of our recent cytogenetic analysis peformed in 2015 on this patient using the multicolor fluorescence in situ hybridization (mFISH) technique. Our results showed that both reciprocal and non-reciprocal translocations persisted at higher frequencies in the patient than those reported in 2012. Persistence of structural aberrations for more than two decades indicate that these aberrations might have originated from long-lived T-lymphocytes or hematopoietic stem cells. Our study suggests that the long-term persistence of chromosome translocations in circulating lymphocytes can be useful for monitoring the extent of RIT-induced chromosomal instability several years after exposure and for estimating the cumulative absorbed dose after multiple RITs for retrospective biodosimetry purposes. This is perhaps the first and longest follow-up study documenting the persistence of cytogenetic damage for 21 years after internal radiation exposure. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Plasma processing conditions substantially influence circulating microRNA biomarker levels.

PubMed

Cheng, Heather H; Yi, Hye Son; Kim, Yeonju; Kroh, Evan M; Chien, Jason W; Eaton, Keith D; Goodman, Marc T; Tait, Jonathan F; Tewari, Muneesh; Pritchard, Colin C

2013-01-01

Circulating, cell-free microRNAs (miRNAs) are promising candidate biomarkers, but optimal conditions for processing blood specimens for miRNA measurement remain to be established. Our previous work showed that the majority of plasma miRNAs are likely blood cell-derived. In the course of profiling lung cancer cases versus healthy controls, we observed a broad increase in circulating miRNA levels in cases compared to controls and that higher miRNA expression correlated with higher platelet and particle counts. We therefore hypothesized that the quantity of residual platelets and microparticles remaining after plasma processing might impact miRNA measurements. To systematically investigate this, we subjected matched plasma from healthy individuals to stepwise processing with differential centrifugation and 0.22 µm filtration and performed miRNA profiling. We found a major effect on circulating miRNAs, with the majority (72%) of detectable miRNAs substantially affected by processing alone. Specifically, 10% of miRNAs showed 4-30x variation, 46% showed 30-1,000x variation, and 15% showed >1,000x variation in expression solely from processing. This was predominantly due to platelet contamination, which persisted despite using standard laboratory protocols. Importantly, we show that platelet contamination in archived samples could largely be eliminated by additional centrifugation, even in frozen samples stored for six years. To minimize confounding effects in microRNA biomarker studies, additional steps to limit platelet contamination for circulating miRNA biomarker studies are necessary. We provide specific practical recommendations to help minimize confounding variation attributable to plasma processing and platelet contamination.

Multimillennium changes in dissolved oxygen under global warming: results from an AOGCM and offline ocean biogeochemical model

NASA Astrophysics Data System (ADS)

Yamamoto, A.; Abe-Ouchi, A.; Shigemitsu, M.; Oka, A.; Takahashi, K.; Ohgaito, R.; Yamanaka, Y.

2016-12-01

Long-term oceanic oxygen change due to global warming is still unclear; most future projections (such as CMIP5) are only performed until 2100. Indeed, few previous studies using conceptual models project oxygen change in the next thousands of years, showing persistent global oxygen reduction by about 30% in the next 2000 years, even after atmospheric carbon dioxide stops rising. Yet, these models cannot sufficiently represent the ocean circulation change: the key driver of oxygen change. Moreover, considering serious effect oxygen reduction has on marine life and biogeochemical cycling, long-term oxygen change should be projected for higher validity. Therefore, we used a coupled atmosphere-ocean general circulation model (AOGCM) and an offline ocean biogeochemical model, investigating realistic long-term changes in oceanic oxygen concentration and ocean circulation. We integrated these models for 2000 years under atmospheric CO2 doubling and quadrupling. After global oxygen reduction in the first 500 years, oxygen concentration in deep ocean globally recovers and overshoots, despite surface oxygen decrease and weaker Atlantic Meridional Overturning Circulation. Deep ocean convection in the Weddell Sea recovers and overshoots, after initial cessation. Thus, enhanced deep convection and associated Antarctic Bottom Water supply oxygen-rich surface waters to deep ocean, resulting global deep ocean oxygenation. We conclude that the change in ocean circulation in the Southern Ocean potentially drives millennial-scale oxygenation in the deep ocean; contrary to past reported long-term oxygen reduction and general expectation. In presentation, we will discuss the mechanism of response of deep ocean convection in the Weddell Sea and show the volume changes of hypoxic waters.

Rodent heart failure models do not reflect the human circulating microRNA signature in heart failure.

PubMed

Vegter, Eline L; Ovchinnikova, Ekaterina S; Silljé, Herman H W; Meems, Laura M G; van der Pol, Atze; van der Velde, A Rogier; Berezikov, Eugene; Voors, Adriaan A; de Boer, Rudolf A; van der Meer, Peter

2017-01-01

We recently identified a set of plasma microRNAs (miRNAs) that are downregulated in patients with heart failure in comparison with control subjects. To better understand their meaning and function, we sought to validate these circulating miRNAs in 3 different well-established rat and mouse heart failure models, and correlated the miRNAs to parameters of cardiac function. The previously identified let-7i-5p, miR-16-5p, miR-18a-5p, miR-26b-5p, miR-27a-3p, miR-30e-5p, miR-199a-3p, miR-223-3p, miR-423-3p, miR-423-5p and miR-652-3p were measured by means of quantitative real time polymerase chain reaction (qRT-PCR) in plasma samples of 8 homozygous TGR(mREN2)27 (Ren2) transgenic rats and 8 (control) Sprague-Dawley rats, 6 mice with angiotensin II-induced heart failure (AngII) and 6 control mice, and 8 mice with ischemic heart failure and 6 controls. Circulating miRNA levels were compared between the heart failure animals and healthy controls. Ren2 rats, AngII mice and mice with ischemic heart failure showed clear signs of heart failure, exemplified by increased left ventricular and lung weights, elevated end-diastolic left ventricular pressures, increased expression of cardiac stress markers and reduced left ventricular ejection fraction. All miRNAs were detectable in plasma from rats and mice. No significant differences were observed between the circulating miRNAs in heart failure animals when compared to the healthy controls (all P>0.05) and no robust associations with cardiac function could be found. The previous observation that miRNAs circulate in lower levels in human patients with heart failure could not be validated in well-established rat and mouse heart failure models. These results question the translation of data on human circulating miRNA levels to experimental models, and vice versa the validity of experimental miRNA data for human heart failure.

Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya.

PubMed

Kiyuka, Patience K; Agoti, Charles N; Munywoki, Patrick K; Njeru, Regina; Bett, Anne; Otieno, James R; Otieno, Grieven P; Kamau, Everlyn; Clark, Taane G; van der Hoek, Lia; Kellam, Paul; Nokes, D James; Cotten, Matthew

2018-05-05

Human coronavirus NL63 (HCoV-NL63) is a globally endemic pathogen causing mild and severe respiratory tract infections with reinfections occurring repeatedly throughout a lifetime. Nasal samples were collected in coastal Kenya through community-based and hospital-based surveillance. HCoV-NL63 was detected with multiplex real-time reverse transcription PCR, and positive samples were targeted for nucleotide sequencing of the spike (S) protein. Additionally, paired samples from 25 individuals with evidence of repeat HCoV-NL63 infection were selected for whole-genome virus sequencing. HCoV-NL63 was detected in 1.3% (75/5573) of child pneumonia admissions. Two HCoV-NL63 genotypes circulated in Kilifi between 2008 and 2014. Full genome sequences formed a monophyletic clade closely related to contemporary HCoV-NL63 from other global locations. An unexpected pattern of repeat infections was observed with some individuals showing higher viral titers during their second infection. Similar patterns for 2 other endemic coronaviruses, HCoV-229E and HCoV-OC43, were observed. Repeat infections by HCoV-NL63 were not accompanied by detectable genotype switching. In this coastal Kenya setting, HCoV-NL63 exhibited low prevalence in hospital pediatric pneumonia admissions. Clade persistence with low genetic diversity suggest limited immune selection, and absence of detectable clade switching in reinfections indicates initial exposure was insufficient to elicit a protective immune response.

A blood circulation model for reference man

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leggett, R.W.; Eckerman, K.F.; Williams, L.R.

This paper describes a dynamic blood circulation model that predicts the movement and gradual dispersal of a bolus of material in the circulation after its intravascular injection into an adult human. The main purpose of the model is to improve the dosimetry of internally deposited radionuclides that decay in the circulation to a significant extent. The total blood volume is partitioned into the blood contents of 24 separate organs or tissues, right heart chambers, left heart chambers, pulmonary circulation, arterial outflow to the systemic tissues (aorta and large arteries), and venous return from the systemic tissues (large veins). As amore » compromise between physical reality and computational simplicity, the circulation of blood is viewed as a system of first-order transfers between blood pools, with the delay time depending on the mean transit time across the pool. The model allows consideration of incomplete, tissue-dependent extraction of material during passage through the circulation and return of material from tissues to plasma.« less

CHANGES IN HIPPOCAMPAL SPINE DENSITY AND PROTEIN KINASE C ISOFORMS FOLLOWING DEVELOPMENTAL EXPOSURE TO A MIXTURE OF PERSISTENT CHEMICALS.

EPA Science Inventory

Polychlorinated biphenyls (PCBs) offer a unique model to understand the major issues related to complex environmental mixtures of persistent chemicals. These pollutants are ubiquitous, persistent, bioaccumulate in human body through the food chain, and exist as mixtures of severa...

Characterization of Different Microbubbles in Assisting Focused Ultrasound-Induced Blood-Brain Barrier Opening

NASA Astrophysics Data System (ADS)

Wu, Sheng-Kai; Chu, Po-Chun; Chai, Wen-Yen; Kang, Shih-Tsung; Tsai, Chih-Hung; Fan, Ching-Hsiang; Yeh, Chih-Kuang; Liu, Hao-Li

2017-04-01

Microbubbles (MBs) serve as a critical catalyst to amplify local cavitation in CNS capillary lumen to facilitate focused ultrasound (FUS) to transiently open the blood-brain barrier (BBB). However, limited understanding is available regarding the effect of different microbubbles to induce BBB opening. The aim of this study is to characterize different MBs on their effect in FUS-induced BBB opening. Three MBs, SonoVue, Definity, and USphere, were tested, with 0.4-MHz FUS exposure at 0.62-1.38 of mechanical index (MI) on rats. Evans blue, dynamic contrast-enhanced (DCE) MRI and small-animal ultrasound imaging were used as surrogates to allow molecule-penetrated quantification, BBB-opened observation, and MBs circulation/persistence. Cavitation activity was measured via the passive cavitation detection (PCD) setup to correlate with the exposure level and the histological effect. Under given and identical MB concentrations, the three MBs induced similar and equivalent BBB-opening effects and persistence. In addition, a treatment paradigm by adapting exposure time is proposed to compensate MB decay to retain the persistence of BBB-opening efficiency in multiple FUS exposures. The results potentially improve understanding of the equivalence among MBs in focused ultrasound CNS drug delivery, and provide an effective strategy for securing persistence in this treatment modality.

Antitumor Activity Associated with Prolonged Persistence of Adoptively Transferred NY-ESO-1c259T cells in Synovial Sarcoma.

PubMed

D'Angelo, Sandra P; Melchiori, Luca; Merchant, Melinda S; Bernstein, Donna B; Glod, John; Kaplan, Rosandra N; Grupp, Stephan A; Tap, William D; Chagin, Karen; Binder, Gwendolyn K; Basu, Samik; Lowther, Daniel E; Wang, Ruoxi; Bath, Natalie; Tipping, Alex; Betts, Gareth; Ramachandran, Indu; Navenot, Jean-Marc; Zhang, Hua; Wells, Daniel K; Van Winkle, Erin; Kari, Gabor; Trivedi, Trupti; Holdich, Tom; Pandite, Lini N; Amado, Rafael; Mackall, Crystal L

2018-06-11

We evaluated safety and activity of autologous T cells expressing NY-ESO-1c259, an affinity-enhanced T cell receptor (TCR) recognizing an HLA-A2-restricted NY-ESO-1/LAGE-1a-derived peptide, in patients with metastatic synovial sarcoma (NY-ESO-1c259T cells). Confirmed antitumor responses occurred in 50% of patients (6/12) and were characterized by tumor shrinkage over several months. Circulating NY-ESO-1c259T cells were present post-infusion in all patients and persisted for at least 6 months in all responders. Most infused NY-ESO-1c259T cells exhibited an effector memory phenotype following the ex vivo expansion, but the persisting pools comprised largely central memory and stem cell memory subsets, which remained polyfunctional and showed no evidence for T cell exhaustion despite persistent tumor burdens. Next generation sequencing of endogenous TCRs in CD8+ NY-ESO-1c259T cells revealed clonal diversity without contraction over time. These data suggest that regenerative pools of NY-ESO-1c259T cells produced a continuing supply of effector cells to mediate sustained, clinically meaningful antitumor effects. Copyright ©2018, American Association for Cancer Research.

[From persistence to symbiosis of microorganisms].

PubMed

Bukharin, O V

2012-01-01

Primary results of study of problem of microorganism persistence over the last 2 decades on 7 all-Russian conferences in Orenburg are examined in the article. Milestones of both fundamental research and practically significant studies are designated, the role of persistent potential of microorganisms in infectious pathology is evaluated. The emerging turn of studies from persistence to symbiosis is consonant with the idea of international project "Human microbiom" and allows to use the persistent potential of microorganisms as one of the instruments of resolving issues of infectology.

Molecular epidemiology of WU polyomavirus in hospitalized children with acute respiratory tract infection in China.

PubMed

Zhu, Teng; Lu, Qing-Bin; Zhang, Shu-Yan; Wo, Ying; Zhuang, Lu; Zhang, Pan-He; Zhang, Xiao-Ai; Wei, Wei; Liu, Wei

2017-05-01

To explore the molecular epidemiology and clinical characteristics of Washington University polyomavirus (WUPyV) infection in pediatric patients with acute respiratory tract infections in China. A laboratory surveillance was performed to recruit pediatric patients with acute respiratory tract infections. WUPyV was detected using real-time PCR and complete genome was sequenced for randomly selected positive nasopharyngeal aspirate. Altogether 122 (7.5%) of 1617 children found to be infected with WUPyV and 88 (72.1%) were coinfected with other viruses during 2012-2015. The phylogenetic analysis showed that 14 strains from our study formed two new clusters (Id and IIIc) within the Branch I and Branch III, respectively. WUPyV is persistently circulating in China. Surveillance on WUPyV infection in wider areas and long persistence is warranted.

Weakening of tropical Pacific atmospheric circulation due to anthropogenic forcing

NASA Astrophysics Data System (ADS)

Vecchi, Gabriel A.; Soden, Brian J.; Wittenberg, Andrew T.; Held, Isaac M.; Leetmaa, Ants; Harrison, Matthew J.

2006-05-01

Since the mid-nineteenth century the Earth's surface has warmed, and models indicate that human activities have caused part of the warming by altering the radiative balance of the atmosphere. Simple theories suggest that global warming will reduce the strength of the mean tropical atmospheric circulation. An important aspect of this tropical circulation is a large-scale zonal (east-west) overturning of air across the equatorial Pacific Ocean-driven by convection to the west and subsidence to the east-known as the Walker circulation. Here we explore changes in tropical Pacific circulation since the mid-nineteenth century using observations and a suite of global climate model experiments. Observed Indo-Pacific sea level pressure reveals a weakening of the Walker circulation. The size of this trend is consistent with theoretical predictions, is accurately reproduced by climate model simulations and, within the climate models, is largely due to anthropogenic forcing. The climate model indicates that the weakened surface winds have altered the thermal structure and circulation of the tropical Pacific Ocean. These results support model projections of further weakening of tropical atmospheric circulation during the twenty-first century.

Dengue virus in sub-tropical northern and central Viet Nam: population immunity and climate shape patterns of viral invasion and maintenance.

PubMed

Rabaa, Maia A; Simmons, Cameron P; Fox, Annette; Le, Mai Quynh; Nguyen, Thuy Thi Thu; Le, Hai Yen; Gibbons, Robert V; Nguyen, Xuyen Thanh; Holmes, Edward C; Aaskov, John G

2013-01-01

Dengue virus transmission occurs in both epidemic and endemic cycles across tropical and sub-tropical regions of the world. Incidence is particularly high in much of Southeast Asia, where hyperendemic transmission plagues both urban and rural populations. However, endemicity has not been established in some areas with climates that may not support year-round viral transmission. An understanding of how dengue viruses (DENV) enter these environments and whether the viruses persist in inapparent local transmission cycles is central to understanding how dengue emerges in areas at the margins of endemic transmission. Dengue is highly endemic in tropical southern Vietnam, while increasingly large seasonal epidemics have occurred in northern Viet Nam over the last decade. We have investigated the spread of DENV-1 throughout Vietnam to determine the routes by which the virus enters northern and central regions of the country. Phylogeographic analysis of 1,765 envelope (E) gene sequences from Southeast Asia revealed frequent movement of DENV between neighboring human populations and strong local clustering of viral lineages. Long-distance migration of DENV between human population centers also occurred regularly and on short time-scales, indicating human-mediated viral invasion into northern Vietnam. Human populations in southern Vietnam were found to be the primary source of DENV circulating throughout the country, while central and northern Vietnam acted as sink populations, likely due to reduced connectedness to other populations in the case of the central regions and to the influence of temperature variability on DENV replication and vector survival and competence in the north. Finally, phylogeographic analyses suggested that viral movement follows a gravity model and indicates that population immunity and physical and economic connections between populations may play important roles in shaping patterns of DENV transmission.

Dengue Virus in Sub-tropical Northern and Central Viet Nam: Population Immunity and Climate Shape Patterns of Viral Invasion and Maintenance

PubMed Central

Rabaa, Maia A.; Simmons, Cameron P.; Fox, Annette; Le, Mai Quynh; Nguyen, Thuy Thi Thu; Le, Hai Yen; Gibbons, Robert V.; Nguyen, Xuyen Thanh; Holmes, Edward C.; Aaskov, John G.

2013-01-01

Dengue virus transmission occurs in both epidemic and endemic cycles across tropical and sub-tropical regions of the world. Incidence is particularly high in much of Southeast Asia, where hyperendemic transmission plagues both urban and rural populations. However, endemicity has not been established in some areas with climates that may not support year-round viral transmission. An understanding of how dengue viruses (DENV) enter these environments and whether the viruses persist in inapparent local transmission cycles is central to understanding how dengue emerges in areas at the margins of endemic transmission. Dengue is highly endemic in tropical southern Vietnam, while increasingly large seasonal epidemics have occurred in northern Viet Nam over the last decade. We have investigated the spread of DENV-1 throughout Vietnam to determine the routes by which the virus enters northern and central regions of the country. Phylogeographic analysis of 1,765 envelope (E) gene sequences from Southeast Asia revealed frequent movement of DENV between neighboring human populations and strong local clustering of viral lineages. Long-distance migration of DENV between human population centers also occurred regularly and on short time-scales, indicating human-mediated viral invasion into northern Vietnam. Human populations in southern Vietnam were found to be the primary source of DENV circulating throughout the country, while central and northern Vietnam acted as sink populations, likely due to reduced connectedness to other populations in the case of the central regions and to the influence of temperature variability on DENV replication and vector survival and competence in the north. Finally, phylogeographic analyses suggested that viral movement follows a gravity model and indicates that population immunity and physical and economic connections between populations may play important roles in shaping patterns of DENV transmission. PMID:24340118

The persistence of human DNA in soil following surface decomposition.

PubMed

Emmons, Alexandra L; DeBruyn, Jennifer M; Mundorff, Amy Z; Cobaugh, Kelly L; Cabana, Graciela S

2017-09-01

Though recent decades have seen a marked increase in research concerning the impact of human decomposition on the grave soil environment, the fate of human DNA in grave soil has been relatively understudied. With the purpose of supplementing the growing body of literature in forensic soil taphonomy, this study assessed the relative persistence of human DNA in soil over the course of decomposition. Endpoint PCR was used to assess the presence or absence of human nuclear and mitochondrial DNA, while qPCR was used to evaluate the quantity of human DNA recovered from the soil beneath four cadavers at the University of Tennessee's Anthropology Research Facility (ARF). Human nuclear DNA from the soil was largely unrecoverable, while human mitochondrial DNA was detectable in the soil throughout all decomposition stages. Mitochondrial DNA copy abundances were not significantly different between decomposition stages and were not significantly correlated to soil edaphic parameters tested. There was, however, a significant positive correlation between mitochondrial DNA copy abundances and the human associated bacteria, Bacteroides, as estimated by 16S rRNA gene abundances. These results show that human mitochondrial DNA can persist in grave soil and be consistently detected throughout decomposition. Copyright © 2017 The Chartered Society of Forensic Sciences. Published by Elsevier B.V. All rights reserved.

Time scales and mechanisms of estuarine variability, a synthesis from studies of San Francisco Bay

USGS Publications Warehouse

Cloern, J.E.; Nichols, F.H.

1985-01-01

This review of the preceding papers suggests that temporal variability in San Francisco Bay can be characterized by four time scales (hours, days-weeks, months, years) and associated with at least four mechanisms (variations in freshwater inflow, tides, wind, and exchange with coastal waters). The best understood component of temporal variability is the annual cycle, which is most obviously influenced by seasonal variations in freshwater inflow. The winter season of high river discharge is characterized by: large-scale redistribution of the salinity field (e.g. the upper estuary becomes a riverine system); enhanced density stratification and gravitational circulation with shortened residence times in the bay; decreased tissue concentrations of some contaminants (e.g. copper) in resident bivalves; increased estuarine inputs of river-borne materials such as dissolved inorganic nutrients (N, P, Si), suspended sediments, and humic materials; radical redistributions of pelagic organisms such as copepods and fish; low phutoplankton biomass and primary productivity in the upper estuary; and elimination of freshwater-intolerant species of macroalgae and benthic infauna from the upper estuary. Other mechanisms modulate this river-driven annual cycle: (1) wind speed is highly seasonal (strongest in summer) and causes seasonal variations in atmosphere-water column exchange of dissolved gases, resuspension, and the texture of surficial sediments; (2) seasonal variations in the coastal ocean (e.g. the spring-summer upwelling season) influence species composition of plankton and nutrient concentrations that are advected into the bay; and (3) the annual temperature cycle influences a few selected features (e.g. production and hatching of copepod resting eggs). Much of the interannual variability in San Francisco Bay is also correlated with freshwater inflow: wet years with persistently high river discharge are characterized by persistent winter-type conditions. Mechanisms of short-term variability are not as well understood, although some responses to storm events (pulses in residual currents from wind forcing, erosion of surficial sediments by wind waves, redistribution of fish populations) and the neap-spring tidal cycle (enhanced salinity stratification, gravitational circulation, and phytoplankton biomass during neap tides) have been quantified. In addition to these somewhat predictable features of variability are (1) largely unexplained episodic events (e.g. anomalous blooms of drift macroalgae), and (2) long-term trends directly attributable to human activities (e.g. introduction of exotic species that become permanent members of the biota). ?? 1985 Dr W. Junk Publishers.

Passive cavitation detection during pulsed HIFU exposures of ex vivo tissues and in vivo mouse pancreatic tumors.

PubMed

Li, Tong; Chen, Hong; Khokhlova, Tatiana; Wang, Yak-Nam; Kreider, Wayne; He, Xuemei; Hwang, Joo Ha

2014-07-01

Pulsed high-intensity focused ultrasound (pHIFU) has been shown to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rare factional focal pressures (1-12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms and pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KrasLSL.G12 D/+; p53 R172 H/+; PdxCretg/+ (KPC) mice and closely re-capitulate human disease in their morphology. The cavitation threshold, defined at 50% cavitation probability, was found to vary broadly among the investigated tissues (within 2.5-10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but it decreased rapidly and stopped over the first few pulses ex vivo. Cavitation activity depended on the interplay between the destruction and circulation of cavitation nuclei, which are not only used up by HIFU treatment but also replenished or carried away by circulation in vivo. These findings are important for treatment planning and optimization in pHIFU-induced drug delivery, in particular for pancreatic tumors. Published by Elsevier Inc.

Associations between persistent organic pollutants and metabolic syndrome in morbidly obese individuals.

PubMed

Dusanov, S; Ruzzin, J; Kiviranta, H; Klemsdal, T O; Retterstøl, L; Rantakokko, P; Airaksinen, R; Djurovic, S; Tonstad, S

2018-03-13

Persons with "metabolically healthy" obesity may develop cardiometabolic complications at a lower rate than equally obese persons with evident metabolic syndrome. Even morbidly obese individuals vary in risk profile. Persistent organic pollutants (POPs) are widespread environmental chemicals that impair metabolic homeostasis. We explored whether prevalence of metabolic syndrome in morbidly obese individuals is associated with serum concentrations of POPs. A cross-sectional study among 161 men and 270 women with BMI >35 kg/m 2 and comorbidity, or >40 kg/m 2 . Circulating concentrations of 15 POPs were stratified by number of metabolic syndrome components. In multiple logistic regression analysis odds ratios between top quartile POPs and metabolic risk factors versus POPs below the top quartile were calculated adjusting for age, gender, body mass index, smoking status, alcohol consumption and cholesterol concentrations. Age-adjusted concentrations of trans-nonachlor and dioxin-like and non-dioxin-like polychlorinated biphenyls (PCBs) increased with number of metabolic syndrome components in both genders (p < 0.001), while the organochlorine pesticides HCB, β-HCH and p,p'DDE increased only in women (p < 0.008). Organochlorine pesticides in the top quartile were associated with metabolic syndrome as were dioxin-like and non-dioxin-like PCBs (OR 2.3 [95% CI 1.3-4.0]; OR 2.5 [95% CI 1.3-4.8] and 2.0 [95% CI 1.1-3.8], respectively). Organochlorine pesticides were associated with HDL cholesterol and glucose (OR = 2.0 [95% CI = 1.1-3.4]; 2.4 [95% CI = 1.4-4.0], respectively). Dioxin-like PCBs were associated with diastolic blood pressure, glucose and homeostatic model assessment-insulin resistance index (OR = 2.0 [95% CI = 1.1-3.6], 2.1 [95% CI = 1.2-3.6] and 2.1 [95% CI = 1.0-4.3], respectively). In subjects with morbid obesity, metabolic syndrome was related to circulating levels of organochlorine pesticides and PCBs suggesting that these compounds aggravate clinically relevant complications of obesity. Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Circulatory shear flow alters the viability and proliferation of circulating colon cancer cells

NASA Astrophysics Data System (ADS)

Fan, Rong; Emery, Travis; Zhang, Yongguo; Xia, Yuxuan; Sun, Jun; Wan, Jiandi

2016-06-01

During cancer metastasis, circulating tumor cells constantly experience hemodynamic shear stress in the circulation. Cellular responses to shear stress including cell viability and proliferation thus play critical roles in cancer metastasis. Here, we developed a microfluidic approach to establish a circulatory microenvironment and studied circulating human colon cancer HCT116 cells in response to a variety of magnitude of shear stress and circulating time. Our results showed that cell viability decreased with the increase of circulating time, but increased with the magnitude of wall shear stress. Proliferation of cells survived from circulation could be maintained when physiologically relevant wall shear stresses were applied. High wall shear stress (60.5 dyne/cm2), however, led to decreased cell proliferation at long circulating time (1 h). We further showed that the expression levels of β-catenin and c-myc, proliferation regulators, were significantly enhanced by increasing wall shear stress. The presented study provides a new insight to the roles of circulatory shear stress in cellular responses of circulating tumor cells in a physiologically relevant model, and thus will be of interest for the study of cancer cell mechanosensing and cancer metastasis.

A machine-learned analysis of human gene polymorphisms modulating persisting pain points at major roles of neuroimmune processes.

PubMed

Kringel, Dario; Lippmann, Catharina; Parnham, Michael J; Kalso, Eija; Ultsch, Alfred; Lötsch, Jörn

2018-06-19

Human genetic research has implicated functional variants of more than one hundred genes in the modulation of persisting pain. Artificial intelligence and machine learning techniques may combine this knowledge with results of genetic research gathered in any context, which permits the identification of the key biological processes involved in chronic sensitization to pain. Based on published evidence, a set of 110 genes carrying variants reported to be associated with modulation of the clinical phenotype of persisting pain in eight different clinical settings was submitted to unsupervised machine-learning aimed at functional clustering. Subsequently, a mathematically supported subset of genes, comprising those most consistently involved in persisting pain, was analyzed by means of computational functional genomics in the Gene Ontology knowledgebase. Clustering of genes with evidence for a modulation of persisting pain elucidated a functionally heterogeneous set. The situation cleared when the focus was narrowed to a genetic modulation consistently observed throughout several clinical settings. On this basis, two groups of biological processes, the immune system and nitric oxide signaling, emerged as major players in sensitization to persisting pain, which is biologically highly plausible and in agreement with other lines of pain research. The present computational functional genomics-based approach provided a computational systems-biology perspective on chronic sensitization to pain. Human genetic control of persisting pain points to the immune system as a source of potential future targets for drugs directed against persisting pain. Contemporary machine-learned methods provide innovative approaches to knowledge discovery from previous evidence. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Modern embalming, circulation of fluids, and the voyage through the human arterial system: Carl L. Barnes and the culture of immortality in America.

PubMed

Podgorny, Irina

2011-01-01

By considering the work of American embalmer, lawyer, and physician Carl Lewis Barnes (1872-1927), this paper analyzes the emergence of modern embalming in America. Barnes experimented with and exhibited the techniques by which embalming fluids travelled into the most remote cavities of the human body. In this sense, modem embalmers based their skills and methods on experimental medicine, turning the anatomy of blood vessels, physiology of circulation, and composition of blood into a circuit that allowed embalming fluids to move throughout the corpse. Embalmers in the late 19th century took ownership of the laws of hydrodynamics and the physiology of blood circulation to market their fluids and equipment, thus playing the role of physiologists of death, performing and demonstrating physiological experiments with dead bodies.

Do Southern Ocean Cloud Feedbacks Matter for 21st Century Warming?

NASA Astrophysics Data System (ADS)

Frey, W. R.; Maroon, E. A.; Pendergrass, A. G.; Kay, J. E.

2017-12-01

Cloud phase improvements in a state-of-the-art climate model produce a large 1.5 K increase in equilibrium climate sensitivity (ECS, the surface warming in response to instantaneously doubled CO2) via extratropical shortwave cloud feedbacks. Here we show that the same model improvements produce only a small surface warming increase in a realistic 21st century emissions scenario. The small 21st century warming increase is attributed to extratropical ocean heat uptake. Southern Ocean mean-state circulation takes up heat while a slowdown in North Atlantic circulation acts as a feedback to slow surface warming. Persistent heat uptake by extratropical oceans implies that extratropical cloud biases may not be as important to 21st century warming as biases in other regions. Observational constraints on cloud phase and shortwave radiation that produce a large ECS increase do not imply large changes in 21st century warming.

The absence of an Atlantic imprint on the multidecadal variability of wintertime European temperature.

PubMed

Yamamoto, Ayako; Palter, Jaime B

2016-03-15

Northern Hemisphere climate responds sensitively to multidecadal variability in North Atlantic sea surface temperature (SST). It is therefore surprising that an imprint of such variability is conspicuously absent in wintertime western European temperature, despite that Europe's climate is strongly influenced by its neighbouring ocean, where multidecadal variability in basin-average SST persists in all seasons. Here we trace the cause of this missing imprint to a dynamic anomaly of the atmospheric circulation that masks its thermodynamic response to SST anomalies. Specifically, differences in the pathways Lagrangian particles take to Europe during anomalous SST winters suppress the expected fluctuations in air-sea heat exchange accumulated along those trajectories. Because decadal variability in North Atlantic-average SST may be driven partly by the Atlantic Meridional Overturning Circulation (AMOC), the atmosphere's dynamical adjustment to this mode of variability may have important implications for the European wintertime temperature response to a projected twenty-first century AMOC decline.

Enzootic Transmission of Yellow Fever Virus in Peru

PubMed Central

Bryant, Juliet; Wang, Heiman; Cabezas, Cesar; Ramirez, Gladys; Watts, Douglas; Russell, Kevin

2003-01-01

The prevailing paradigm of yellow fever virus (YFV) ecology in South America is that of wandering epizootics. The virus is believed to move from place to place in epizootic waves involving monkeys and mosquitoes, rather than persistently circulating within particular locales. After a large outbreak of YFV illness in Peru in 1995, we used phylogenetic analyses of virus isolates to reexamine the hypothesis of virus movement. We sequenced a 670-nucleotide fragment of the prM/E gene region of from 25 Peruvian YFV samples collected from 1977 to 1999, and delineated six clades representing the states (Departments) of Puno, Pasco, Junin, Ayacucho, San Martin/Huanuco, and Cusco. The concurrent appearance of at least four variants during the 1995 epidemic and the genetic stability of separate virus lineages over time, indicate that Peruvian YFV is locally maintained and circulates continuously in discrete foci of enzootic transmission. PMID:12967489

The Role of Bacterial Chaperones in the Circulative Transmission of Plant Viruses by Insect Vectors

PubMed Central

Kliot, Adi; Ghanim, Murad

2013-01-01

Persistent circulative transmission of plant viruses involves complex interactions between the transmitted virus and its insect vector. Several studies have shown that insect vector proteins are involved in the passage and the transmission of the virus. Interestingly, proteins expressed by bacterial endosymbionts that reside in the insect vector, were also shown to influence the transmission of these viruses. Thus far, the transmission of two plant viruses that belong to different virus genera was shown to be facilitated by a bacterial chaperone protein called GroEL. This protein was shown to be implicated in the transmission of Potato leafroll virus (PLRV) by the green peach aphid Myzus persicae, and the transmission of Tomato yellow leaf curl virus (TYLCV) by the sweetpotato whitefly Bemisia tabaci. These tri-trophic levels of interactions and their possible evolutionary implications are reviewed. PMID:23783810

Ensemble formulation of surface fluxes and improvement in evapotranspiration and cloud parameterizations in a GCM. [General Circulation Model

NASA Technical Reports Server (NTRS)

Sud, Y. C.; Smith, W. E.

1984-01-01

The influence of some modifications to the parameters of the current general circulation model (GCM) is investigated. The aim of the modifications was to eliminate strong occasional bursts of oscillations in planetary boundary layer (PBL) fluxes. Smoothly varying bulk aerodynamic friction and heat transport coefficients were found by ensemble averaging of the PBL fluxes in the current GCM. A comparison was performed of the simulations of the modified model and the unmodified model. The comparison showed that the surface fluxes and cloudiness in the modified model simulations were much more accurate. The planetary albedo in the model was also realistic. Weaknesses persisted in the models positioning of the Inter-tropical convergence zone (ICTZ) and in the temperature estimates for polar regions. A second simulation of the model following reparametrization of the cloud data showed improved results and these are described in detail.

Human Papilloma Virus Persistence after Cone Excision in Women with Cervical High Grade Squamous Intraepithelial Lesion: A Prospective Study

PubMed Central

Pirtea, Laurențiu; Grigoraş, Dorin; Matusz, Petru; Pirtea, Marilena; Moleriu, Lavinia; Tudor, Anca; Ilina, Răzvan; Secoşan, Cristina; Mazilu, Octavian

2016-01-01

Background. Persistent human papillomavirus (HPV) infection is a necessary event in cervical cancer tumorigenesis. Our objectives were to estimate the rate of HPV infection persistence after large loop excision of the transformation zone (LEEP) in patients with high grade squamous intraepithelial lesions (HSIL) and to investigate if HPV persistence is type related. Methods. We conducted a prospective study on 89 patients with HSIL treated with LEEP. DNA HPV was performed before surgery and at 6, 12, and 18 months after LEEP. Results. Four patients were excluded from the study. The HPV persistence in the remaining 85 patients was 32.95% (6 months), 14.12% (12 months), and 10.59% (18 months). Type 16 had the highest persistence rate, 23.5% (6 months), 11.8% (12 months), and 8.2% (18 months). Coinfection was found to be 54.12% before LEEP and 18.8% (6 months), 4.7% (12 months), and 3.5% (18 months) after LEEP. The rate of coinfections including type 16 was 46.83% of all coinfections. Coinfection including type 16 was not correlated with higher persistence rate compared to infection with type 16 only. Conclusions. HPV infection is not completely eradicated by LEEP in patients with HSIL lesion on PAP smear. HPV persistence after LEEP is influenced by HPV type. HPV type 16 has the highest persistence rate. PMID:27366164

Na+/Taurocholate Cotransporting Polypeptide and Apical Sodium-Dependent Bile Acid Transporter Are Involved in the Disposition of Perfluoroalkyl Sulfonates in Humans and Rats

PubMed Central

Zhao, Wen; Zitzow, Jeremiah D.; Ehresman, David J.; Chang, Shu-Ching; Butenhoff, John L.; Forster, Jameson; Hagenbuch, Bruno

2015-01-01

Among the perfluoroalkyl sulfonates (PFASs), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) have half-lives of several years in humans, mainly due to slow renal clearance and potential hepatic accumulation. Both compounds undergo enterohepatic circulation. To determine whether transporters involved in the enterohepatic circulation of bile acids are also involved in the disposition of PFASs, uptake of perfluorobutane sulfonate (PFBS), PFHxS, and PFOS was measured using freshly isolated human and rat hepatocytes in the absence or presence of sodium. The results demonstrated sodium-dependent uptake for all 3 PFASs. Given that the Na+/taurocholate cotransporting polypeptide (NTCP) and the apical sodium-dependent bile salt transporter (ASBT) are essential for the enterohepatic circulation of bile acids, transport of PFASs was investigated in stable CHO Flp-In cells for human NTCP or HEK293 cells transiently expressing rat NTCP, human ASBT, and rat ASBT. The results demonstrated that both human and rat NTCP can transport PFBS, PFHxS, and PFOS. Kinetics with human NTCP revealed Km values of 39.6, 112, and 130 µM for PFBS, PFHxS, and PFOS, respectively. For rat NTCP Km values were 76.2 and 294 µM for PFBS and PFHxS, respectively. Only PFOS was transported by human ASBT whereas rat ASBT did not transport any of the tested PFASs. Human OSTα/β was also able to transport all 3 PFASs. In conclusion, these results suggest that the long half-live and the hepatic accumulation of PFOS in humans are at least, in part, due to transport by NTCP and ASBT. PMID:26001962

Human Adaptation of Ebola Virus during the West African Outbreak.

PubMed

Urbanowicz, Richard A; McClure, C Patrick; Sakuntabhai, Anavaj; Sall, Amadou A; Kobinger, Gary; Müller, Marcel A; Holmes, Edward C; Rey, Félix A; Simon-Loriere, Etienne; Ball, Jonathan K

2016-11-03

The 2013-2016 outbreak of Ebola virus (EBOV) in West Africa was the largest recorded. It began following the cross-species transmission of EBOV from an animal reservoir, most likely bats, into humans, with phylogenetic analysis revealing the co-circulation of several viral lineages. We hypothesized that this prolonged human circulation led to genomic changes that increased viral transmissibility in humans. We generated a synthetic glycoprotein (GP) construct based on the earliest reported isolate and introduced amino acid substitutions that defined viral lineages. Mutant GPs were used to generate a panel of pseudoviruses, which were used to infect different human and bat cell lines. These data revealed that specific amino acid substitutions in the EBOV GP have increased tropism for human cells, while reducing tropism for bat cells. Such increased infectivity may have enhanced the ability of EBOV to transmit among humans and contributed to the wide geographic distribution of some viral lineages. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Neural Control of the Circulation

ERIC Educational Resources Information Center

Thomas, Gail D.

2011-01-01

The purpose of this brief review is to highlight key concepts about the neural control of the circulation that graduate and medical students should be expected to incorporate into their general knowledge of human physiology. The focus is largely on the sympathetic nerves, which have a dominant role in cardiovascular control due to their effects to…

21 CFR 890.5720 - Water circulating hot or cold pack.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Water circulating hot or cold pack. 890.5720 Section 890.5720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5720 Water...

21 CFR 890.5720 - Water circulating hot or cold pack.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Water circulating hot or cold pack. 890.5720 Section 890.5720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5720 Water...

21 CFR 890.5720 - Water circulating hot or cold pack.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Water circulating hot or cold pack. 890.5720 Section 890.5720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5720 Water...

21 CFR 890.5720 - Water circulating hot or cold pack.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Water circulating hot or cold pack. 890.5720 Section 890.5720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5720 Water...

21 CFR 890.5720 - Water circulating hot or cold pack.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Water circulating hot or cold pack. 890.5720 Section 890.5720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5720 Water...

Minimal residual disease in breast cancer: an overview of circulating and disseminated tumour cells.

PubMed

Tachtsidis, A; McInnes, L M; Jacobsen, N; Thompson, E W; Saunders, C M

2016-08-01

Within the field of cancer research, focus on the study of minimal residual disease (MRD) in the context of carcinoma has grown exponentially over the past several years. MRD encompasses circulating tumour cells (CTCs)-cancer cells on the move via the circulatory or lymphatic system, disseminated tumour cells (DTCs)-cancer cells which have escaped into a distant site (most studies have focused on bone marrow), and resistant cancer cells surviving therapy-be they local or distant, all of which may ultimately give rise to local relapse or overt metastasis. Initial studies simply recorded the presence and number of CTCs and DTCs; however recent advances are allowing assessment of the relationship between their persistence, patient prognosis and the biological properties of MRD, leading to a better understanding of the metastatic process. Technological developments for the isolation and analysis of circulating and disseminated tumour cells continue to emerge, creating new opportunities to monitor disease progression and perhaps alter disease outcome. This review outlines our knowledge to date on both measurement and categorisation of MRD in the form of CTCs and DTCs with respect to how this relates to cancer outcomes, and the hurdles and future of research into both CTCs and DTCs.

Wake structure and wing motion in bat flight

NASA Astrophysics Data System (ADS)

Hubel, Tatjana; Breuer, Kenneth; Swartz, Sharon

2008-11-01

We report on experiments concerning the wake structure and kinematics of bat flight, conducted in a low-speed wind tunnel using time-resolved PIV (200Hz) and 4 high-speed cameras to capture wake and wing motion simultaneously. 16 Lesser dog-faced fruit bats (C. brachyotis) were trained to fly in the wind tunnel at 3-6.5m/s. The PIV recordings perpendicular to the flow stream allowed observing the development of the tip vortex and circulation over the wing beat cycle. Each PIV acquisition sequence is correlated with the respective kinematic history. Circulation within wing beat cycles were often quite repeatable, however variations due to maneuvering of the bat are clearly visible. While no distinct vortex structure was observed at the upper reversal point (defined according the vertical motion of the wrist) a tip vortex was observed to develop in the first third of the downstroke, growing in strength, and persisting during much of the upstroke. Correlated to the presence of a strong tip vortex the circulation has almost constant strength over the middle half of the wing beat. At relatively low flight speeds (3.4 m/s), a closed vortex structure behind the bat is postulated.

Symmetry, stability, and computation of degenerate lasing modes

NASA Astrophysics Data System (ADS)

Liu, David; Zhen, Bo; Ge, Li; Hernandez, Felipe; Pick, Adi; Burkhardt, Stephan; Liertzer, Matthias; Rotter, Stefan; Johnson, Steven G.

2017-02-01

We present a general method to obtain the stable lasing solutions for the steady-state ab initio lasing theory (SALT) for the case of a degenerate symmetric laser in two dimensions (2D). We find that under most regimes (with one pathological exception), the stable solutions are clockwise and counterclockwise circulating modes, generalizing previously known results of ring lasers to all 2D rotational symmetry groups. Our method uses a combination of semianalytical solutions close to lasing threshold and numerical solvers to track the lasing modes far above threshold. Near threshold, we find closed-form expressions for both circulating modes and other types of lasing solutions as well as for their linearized Maxwell-Bloch eigenvalues, providing a simple way to determine their stability without having to do a full nonlinear numerical calculation. Above threshold, we show that a key feature of the circulating mode is its "chiral" intensity pattern, which arises from spontaneous symmetry breaking of mirror symmetry, and whose symmetry group requires that the degeneracy persists even when nonlinear effects become important. Finally, we introduce a numerical technique to solve the degenerate SALT equations far above threshold even when spatial discretization artificially breaks the degeneracy.

Long-term persistence of hormonal adaptations to weight loss.

PubMed

Sumithran, Priya; Prendergast, Luke A; Delbridge, Elizabeth; Purcell, Katrina; Shulkes, Arthur; Kriketos, Adamandia; Proietto, Joseph

2011-10-27

After weight loss, changes in the circulating levels of several peripheral hormones involved in the homeostatic regulation of body weight occur. Whether these changes are transient or persist over time may be important for an understanding of the reasons behind the high rate of weight regain after diet-induced weight loss. We enrolled 50 overweight or obese patients without diabetes in a 10-week weight-loss program for which a very-low-energy diet was prescribed. At baseline (before weight loss), at 10 weeks (after program completion), and at 62 weeks, we examined circulating levels of leptin, ghrelin, peptide YY, gastric inhibitory polypeptide, glucagon-like peptide 1, amylin, pancreatic polypeptide, cholecystokinin, and insulin and subjective ratings of appetite. Weight loss (mean [±SE], 13.5±0.5 kg) led to significant reductions in levels of leptin, peptide YY, cholecystokinin, insulin (P<0.001 for all comparisons), and amylin (P=0.002) and to increases in levels of ghrelin (P<0.001), gastric inhibitory polypeptide (P=0.004), and pancreatic polypeptide (P=0.008). There was also a significant increase in subjective appetite (P<0.001). One year after the initial weight loss, there were still significant differences from baseline in the mean levels of leptin (P<0.001), peptide YY (P<0.001), cholecystokinin (P=0.04), insulin (P=0.01), ghrelin (P<0.001), gastric inhibitory polypeptide (P<0.001), and pancreatic polypeptide (P=0.002), as well as hunger (P<0.001). One year after initial weight reduction, levels of the circulating mediators of appetite that encourage weight regain after diet-induced weight loss do not revert to the levels recorded before weight loss. Long-term strategies to counteract this change may be needed to prevent obesity relapse. (Funded by the National Health and Medical Research Council and others; ClinicalTrials.gov number, NCT00870259.).

Effect of long-term dietary sphingomyelin supplementation on atherosclerosis in mice

PubMed Central

Chung, Rosanna W. S.; Wang, Zeneng; Bursill, Christina A.; Wu, Ben J.; Barter, Philip J.

2017-01-01

Sphingomyelin (SM) levels in the circulation correlate positively with atherosclerosis burden. SM is a ubiquitous component of human diets, but it is unclear if dietary SM increases circulating SM levels. Dietary choline increases atherosclerosis by raising circulating trimethylamine N-oxide (TMAO) levels in mice and humans. As SM has a choline head group, we ask in this study if dietary SM accelerates atherosclerotic lesion development by increasing circulating SM and TMAO levels. Three studies were performed: (Study 1) C57BL/6 mice were maintained on a high fat diet with or without SM supplementation for 4 weeks prior to quantification of serum TMAO and SM levels; (Study 2) atherosclerosis was studied in apoE-/- mice after 16 weeks of a high fat diet without or with SM supplementation and (Study 3) apoE-/- mice were maintained on a chow diet for 19 weeks without or with SM supplementation and antibiotic treatment prior to quantification of atherosclerotic lesions and serum TMAO and SM levels. SM consumption did not increase circulating SM levels or atherosclerosis in high fat-fed apoE-/- mice. Serum TMAO levels in C57BL/6 mice were low and had no effect atherosclerosis lesion development. Dietary SM supplementation significantly reduced atherosclerotic lesion area in the aortic arch of chow-fed apoE-/- mice. This study establishes that dietary SM does not affect circulating SM levels or increase atherosclerosis in high fat-fed apoE-/- mice, but it is anti-atherogenic in chow-fed apoE-/- mice. PMID:29240800

Novel rodent model of breast cancer survival with persistent anxiety-like behavior and inflammation.

PubMed

Pyter, Leah M; Suarez-Kelly, Lorena P; Carson, William E; Kaur, Jasskiran; Bellisario, Joshua; Bever, Savannah R

2017-07-14

Breast cancer survivors are an expanding population that is troubled by lasting mental health problems, including depression and anxiety. These issues reduce quality-of-life throughout survivorhood. Research indicates that tumor biology, cancer treatments, and stress contribute to these mood disturbances. Although the mechanisms underlying these various causes remain under investigation, neuroinflammation is a leading hypothesis. To date, rodent models of recurrence-free tumor survival for understanding mechanisms by which these behavioral issues persist after cancer are lacking. Here, we test the extent to which potential behavioral symptoms persist after mammary tumor removal in mice (i.e., establishment of a cancer survivor model), while also empirically testing the causal role of tumors in the development of neuroinflammatory-mediated affective-like behaviors. Complete surgical resection of a non-metastatic orthotopic, syngeneic mammary tumor reversed tumor-induced increases of circulating cytokines (IL-6, CXCL1, IL-10) and myeloid-derived cells and modulated neuroinflammatory gene expression (Cd11b, Cxcl1). Multiple anxiety-like behaviors and some central and peripheral immune markers persisted or progressed three weeks after tumor resection. Together, these data indicate that persistent behavioral changes into cancer survivorhood may be due, in part, to changes in immunity that remain even after successful tumor removal. This novel survivor paradigm represents an improvement in modeling prevalent cancer survivorship issues and studying the basic mechanisms by which cancer/cancer treatments influence the brain and behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-term administration of inulin-type fructans has no significant lipid-lowering effect in normolipidemic humans.

PubMed

Forcheron, Fabien; Beylot, Michel

2007-08-01

Short-term studies have shown that the addition to diet of inulin-type fructans, a nondigestible carbohydrate, may have a plasma lipid-lowering effect in humans. Whether this beneficial effect persists during long-term administration has not been determined. The study was aimed at determining whether a prolonged (6 months) administration of inulin-type fructans to healthy subjects has a lipid-lowering action. In a double-blind, randomized, placebo-controlled study, 17 healthy subjects were studied before and after 6 months of daily administration of placebo (8 subjects) or 10 g of a mix of inulin and oligofructose (9 subjects). During this 6-month period, they consumed their usual diet and did not modify their everyday way of life. We measured plasma lipid concentrations; cholesterol synthesis and hepatic lipogenesis; and adipose tissue and circulating mononuclear cell messenger RNA concentrations of key regulatory genes of cholesterol metabolism. Compared with the administration of placebo, the administration of inulin-type fructans had no effect on plasma triacylglycerol concentrations and hepatic lipogenesis and induced only a nonsignificant trend for decreased plasma total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol concentration. Cholesterol synthesis was not significantly modified. Of all the messenger RNA concentrations measured, none was significantly modified by the administration of inulin-type fructans. In conclusion, contrary to what was observed in short-term studies, we observed no significant beneficial effect of a long-term (6-month) administration of inulin-type fructans on plasma lipids in healthy human subjects.

Neuroendocrine Factors in the Regulation of Inflammation: Excessive Adiposity and Calorie Restriction

PubMed Central

Fontana, Luigi

2009-01-01

Acute inflammation is usually a self-limited life preserving response, triggered by pathogens and/or traumatic injuries. This transient response normally leads to removal of harmful agents and to healing of the damaged tissues. In contrast, unchecked or chronic inflammation can lead to persistent tissue and organ damage by activated leukocytes, cytokines, or collagen deposition. Excessive energy intake and adiposity cause systemic inflammation, whereas calorie restriction without malnutrition exerts a potent anti-inflammatory effect. As individuals accumulate fat and their adipocytes enlarge, adipose tissue undergoes molecular and cellular alterations, macrophages accumulate, and inflammation ensues. Overweight/obese subjects have significantly higher plasma concentrations of C-reactive protein and several cytokines, including IL-6, IL-8, IL-18, and TNF-alpha. Experimental animals on a chronic CR regimen, instead, have low levels of circulating inflammatory cytokines, low blood lymphocyte levels, reduced production of inflammatory cytokines by the white blood cells in response to stimulation, and cortisol levels in the high normal range. Recent data demonstrate that CR exerts a powerful anti-inflammatory effect also in non-human primates and humans. Multiple metabolic and neuroendocrine mechanisms are responsible for the CR-mediated anti-inflammatory effects, including reduced adiposity and secretion of pro-inflammatory adipokines, enhanced glucocorticoid production, reduced plasma glucose and advanced glycation end-product concentrations, increased parasympathetic tone, and increased ghrelin production. Measuring tissue specific effects of CR using genomic, proteomic and metabolomic techniques in humans will foster the understanding of the complex biological processes involved in the anti-inflammatory and anti-aging effects of CR. PMID:18502597

The repeated introduction of the H3N2 virus from human to swine during 1979-1993 in China.

PubMed

Zhu, Wenfei; Yang, Shuai; Dong, Libo; Yang, Lei; Tang, Jing; Zou, Xiaohui; Chen, Tao; Yang, Jing; Shu, Yuelong

2015-07-01

Limited data are available regarding the swine influenza viruses (SIVs) that circulated in Mainland China prior to the 1990s. Eleven H3N2 virus strains were isolated from swine populations from 1979 to 1992. To determine the origin and tendency of these SIVs, the phylogenetic and antigenic properties of these viruses were analyzed based on the whole genome sequenced and the HI titrations with post-infection ferret antisera against influenza A (H3N2) virus isolates of swine and human origin. The results revealed that these 11 SIVs originated from humans and were not maintained in swine populations, indicating the interspecies transmission from humans to pigs occurred frequently and independently throughout these periods. However, human H3N2 viruses might not have the ability to circulate in pig herds. Copyright © 2015 Elsevier B.V. All rights reserved.

Fundamental bound on the persistence and capacity of short-term memory stored as graded persistent activity.

PubMed

Koyluoglu, Onur Ozan; Pertzov, Yoni; Manohar, Sanjay; Husain, Masud; Fiete, Ila R

2017-09-07

It is widely believed that persistent neural activity underlies short-term memory. Yet, as we show, the degradation of information stored directly in such networks behaves differently from human short-term memory performance. We build a more general framework where memory is viewed as a problem of passing information through noisy channels whose degradation characteristics resemble those of persistent activity networks. If the brain first encoded the information appropriately before passing the information into such networks, the information can be stored substantially more faithfully. Within this framework, we derive a fundamental lower-bound on recall precision, which declines with storage duration and number of stored items. We show that human performance, though inconsistent with models involving direct (uncoded) storage in persistent activity networks, can be well-fit by the theoretical bound. This finding is consistent with the view that if the brain stores information in patterns of persistent activity, it might use codes that minimize the effects of noise, motivating the search for such codes in the brain.

HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy.

PubMed

Honeycutt, Jenna B; Thayer, William O; Baker, Caroline E; Ribeiro, Ruy M; Lada, Steven M; Cao, Youfang; Cleary, Rachel A; Hudgens, Michael G; Richman, Douglas D; Garcia, J Victor

2017-05-01

Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in its hosts and is never eradicated. One major barrier to eradication is that the virus infects multiple cell types that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV pathogenesis; however, their specific role in HIV persistence during long-term suppressive ART has not been established. Using humanized myeloid-only mice (MoM), we demonstrate that HIV infection of tissue macrophages is rapidly suppressed by ART, as reflected by a rapid drop in plasma viral load and a dramatic decrease in the levels of cell-associated viral RNA and DNA. No viral rebound was observed in the plasma of 67% of the ART-treated animals at 7 weeks after ART interruption, and no replication-competent virus was rescued from the tissue macrophages obtained from these animals. In contrast, in a subset of animals (∼33%), a delayed viral rebound was observed that is consistent with the establishment of persistent infection in tissue macrophages. These observations represent the first direct evidence, to our knowledge, of HIV persistence in tissue macrophages in vivo.

Fundamental bound on the persistence and capacity of short-term memory stored as graded persistent activity

PubMed Central

Pertzov, Yoni; Manohar, Sanjay; Husain, Masud; Fiete, Ila R

2017-01-01

It is widely believed that persistent neural activity underlies short-term memory. Yet, as we show, the degradation of information stored directly in such networks behaves differently from human short-term memory performance. We build a more general framework where memory is viewed as a problem of passing information through noisy channels whose degradation characteristics resemble those of persistent activity networks. If the brain first encoded the information appropriately before passing the information into such networks, the information can be stored substantially more faithfully. Within this framework, we derive a fundamental lower-bound on recall precision, which declines with storage duration and number of stored items. We show that human performance, though inconsistent with models involving direct (uncoded) storage in persistent activity networks, can be well-fit by the theoretical bound. This finding is consistent with the view that if the brain stores information in patterns of persistent activity, it might use codes that minimize the effects of noise, motivating the search for such codes in the brain. PMID:28879851

Differential Persistence of Foot-and-Mouth Disease Virus in African Buffalo Is Related to Virus Virulence.

PubMed

Maree, Francois; de Klerk-Lorist, Lin-Mari; Gubbins, Simon; Zhang, Fuquan; Seago, Julian; Pérez-Martín, Eva; Reid, Liz; Scott, Katherine; van Schalkwyk, Louis; Bengis, Roy; Charleston, Bryan; Juleff, Nicholas

2016-05-15

Foot-and-mouth disease (FMD) virus (FMDV) circulates as multiple serotypes and strains in many regions of endemicity. In particular, the three Southern African Territories (SAT) serotypes are maintained effectively in their wildlife reservoir, the African buffalo, and individuals may harbor multiple SAT serotypes for extended periods in the pharyngeal region. However, the exact site and mechanism for persistence remain unclear. FMD in buffaloes offers a unique opportunity to study FMDV persistence, as transmission from carrier ruminants has convincingly been demonstrated for only this species. Following coinfection of naive African buffaloes with isolates of three SAT serotypes from field buffaloes, palatine tonsil swabs were the sample of choice for recovering infectious FMDV up to 400 days postinfection (dpi). Postmortem examination identified infectious virus for up to 185 dpi and viral genomes for up to 400 dpi in lymphoid tissues of the head and neck, focused mainly in germinal centers. Interestingly, viral persistence in vivo was not homogenous, and the SAT-1 isolate persisted longer than the SAT-2 and SAT-3 isolates. Coinfection and passage of these SAT isolates in goat and buffalo cell lines demonstrated a direct correlation between persistence and cell-killing capacity. These data suggest that FMDV persistence occurs in the germinal centers of lymphoid tissue but that the duration of persistence is related to virus replication and cell-killing capacity. Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in domestic livestock and wildlife species. African buffaloes (Syncerus caffer) are the primary carrier hosts of FMDV in African savannah ecosystems, where the disease is endemic. We have shown that the virus persists for up to 400 days in buffaloes and that there is competition between viruses during mixed infections. There was similar competition in cell culture: viruses that killed cells quickly persisted more efficiently in passaged cell cultures. These results may provide a mechanism for the dominance of particular viruses in an ecosystem. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease.

PubMed

Anguiano, Lidia; Riera, Marta; Pascual, Julio; Valdivielso, José Manuel; Barrios, Clara; Betriu, Angels; Mojal, Sergi; Fernández, Elvira; Soler, María José

2015-07-01

Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3-5 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease. Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity. In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients. Circulating ACE2 and ACE activities can be measured in human EDTA-plasma samples with zinc added to recover enzymatic activity. In a CKD population without previous history of CV disease, ACE2 activity from human EDTA-plasma samples directly correlated with the classical CV risk factors namely older age, diabetes and male gender. Our data suggest that circulating ACE2 is altered in CKD patients at risk for CV event. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Postprandial triglyceride-rich lipoproteins promote lipid accumulation and apolipoprotein B-48 receptor transcriptional activity in human circulating and murine bone marrow neutrophils in a fatty acid-dependent manner.

PubMed

Ortega-Gómez, Almudena; Varela, Lourdes M; López, Sergio; Montserrat de la Paz, Sergio; Sánchez, Rosario; Muriana, Francisco J G; Bermúdez, Beatriz; Abia, Rocío

2017-09-01

Postprandial triglyceride-rich lipoproteins (TRLs) promote atherosclerosis. Recent research points the bone marrow (BM) as a primary site in atherosclerosis. We elucidated how the acute administration of monounsaturated fatty acids (MUFAs) MUFAs, omega-3 polyunsaturated fatty acids (PUFAs) PUFAs and saturated fatty acids (SFAs) affects human circulating and murine BM neutrophil lipid accumulation and functionality. Postprandial hypertriglyceridemia was induced in healthy subjects and Apoe -/- mice by the acute administration of dietary fats enriched in MUFAs, PUFAs, or SFAs. Postprandial hypertriglyceridemia increased apolipoprotein-B48 receptor (ApoB48R) transcriptional activity that was linearly correlated with intracellular triglycerides (TGs) TGs accumulation in human circulating and murine BM neutrophils. MUFA and omega-3 PUFAs attenuated ApoB48R gene expression and intracellular TG accumulation compared to SFAs. TRLs induced apoB48R-dependent TG accumulation in human neutrophils ex vivo. Murine BM neutrophils showed a decrease in surface L-selectin and an increase in TNF-α and IL-1β mRNA expressions only after SFAs administration. TRLs enriched in SFAs induced BM neutrophil degranulation ex vivo suggesting cell priming/activation. Postprandial TRLs disrupts the normal biology and function of circulating and BM neutrophils. MUFA- and omega-3 PUFA-rich dietary fats such as virgin olive oil or fish oil has the potential to prevent excessive neutrophil lipid accumulation and activation by targeting the fatty acid composition of TRLs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Human biomonitoring reference values for some non-persistent chemicals in blood and urine derived from the Canadian Health Measures Survey 2009-2013.

PubMed

Khoury, Cheryl; Werry, Kate; Haines, Douglas; Walker, Mike; Malowany, Morie

2018-05-01

The Canadian Health Measures Survey collects nationally representative human biomonitoring data on a suite of chemicals and their metabolites, including many non-persistent chemicals. Data has been collected on non-persistent chemicals, including acrylamide, chlorophenols, environmental phenols and triclocarban, organophosphate insecticides, phthalates, polycyclic aromatic hydrocarbon, pyrethroid insecticides, and volatile organic compounds from 2009 to 2013. Using a systematic approach building on the reference interval concept proposed by the International Federation of Clinical Chemistry and Laboratory Medicine and the International Union of Pure and Applied Chemistry, we derive human biomonitoring reference values (RV 95 s) for these classes of non-persistent chemicals in blood and urine for the general Canadian population. RV 95 s were derived for biomarkers of non-persistent chemicals with widespread detection in Canadians (>66% detection rate). Samples with urinary creatinine levels outside the recommended range of 0.3-3.0 μg/L were excluded. Reference populations were constructed by applying smoking and fasting as exclusion criteria where appropriate. Age and sex were evaluated as possible partitioning criteria and separate RV 95 s were derived for sub-populations in cases where partitioning was deemed necessary. Reference values were derived for 40 biomarkers and represent the first set of RV 95 s for non-persistent chemicals in the general Canadian population. These values provide a measure of the upper margin of background exposure in the general population and can be compared against individual and population human biomonitoring data. RV 95 s can be used to by public health officials to identify individuals with high exposures, and by risk assessors and risk managers to identify atypical exposures or subpopulations with elevated exposures. Crown Copyright © 2018. Published by Elsevier GmbH. All rights reserved.

Radiation therapy induces circulating serum Hsp72 in patients with prostate cancer.

PubMed

Hurwitz, Mark D; Kaur, Punit; Nagaraja, Ganachari M; Bausero, Maria A; Manola, Judith; Asea, Alexzander

2010-06-01

Hsp72 found in the extracellular milieu has been shown to play an important role in immune regulation. The impact of common cancer therapies on extracellular release of Hsp72 however, has been to date undefined. Serum from 13 patients undergoing radiation therapy (XRT) for prostate cancer with or without hormonal therapy (ADT) was measured for levels of circulating serum Hsp72 and pro-inflammatory cytokines (IL-6 and TNF-alpha) using the classical sandwich ELISA technique and the relative expression of CD8(+) T lymphocytes and natural killer (NK) cells was measured using flow cytometry. Mouse orthotopic xenograft of human prostate cancer tumors (DU-145 and PC-3) were used to validate and further characterize the response noted in the clinical setting. The biological significance of tumor released Hsp72 was studied in human dendritic cells (DC) in vitro. Circulating serum Hsp72 levels increased an average of 3.5-fold (median per patient 4.8-fold) with XRT but not with ADT (p=0.0002). Increases in IL-6 (3.3-fold), TNF-alpha (1.8-fold), CD8(+) CTL (2.1-fold) and NK cells (3.2-fold) also occurred. Using PC-3 and DU-145 human prostate cancer xenograft models in mice, we confirmed that XRT induces Hsp72 release primarily from implanted tumors. In vitro studies using supernatant recovered from irradiated human prostate cancer cells point to exosomes containing Hsp72 as a possible stimulator of pro-inflammatory cytokine production and costimulatory molecules expression in human DC. The current study confirms for the first time in an actual clinical setting elevation of circulating serum Hsp72 with XRT. The accompanying studies in mice and in vitro identify the released exosomes containing Hsp72 as playing a pivotal role in stimulating pro-inflammatory immune responses. These findings, if validated, may lead to new treatment paradigms for common human malignancies. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Radiation therapy induces circulating serum Hsp72 in patients with prostate cancer

PubMed Central

Hurwitz, Mark D.; Kaur, Punit; Nagaraja, Ganachari M.; Bausero, Maria A.; Manola, Judith; Asea, Alexzander

2010-01-01

Background and purpose Hsp72 found in the extracellular milieu has been shown to play an important role in immune regulation. The impact of common cancer therapies on extracellular release of Hsp72 however, has been to date undefined. Materials and methods Serum from 13 patients undergoing radiation therapy (XRT) for prostate cancer with or without hormonal therapy (ADT) was measured for levels of circulating serum Hsp72 and pro-inflammatory cytokines (IL-6 and TNF-α) using the classical sandwich ELISA technique and the relative expression of CD8+ T lymphocytes and natural killer (NK) cells was measured using flow cytometry. Mouse orthotopic xenograft of human prostate cancer tumors (DU145 and PC3) were used to validate and further characterize the response noted in the clinical setting. The biological significance of tumor released Hsp72 was studied in human dendritic cells (DC) in vitro. Results Circulating serum Hsp72 levels increased an average of 3.5-fold (median per patient 4.8-fold) with XRT but not with ADT (p = 0.0002). Increases in IL-6 (3.3-fold), TNF-α (1.8-fold), CD8+ CTL (2.1-fold) and NK cells (3.2-fold) also occurred. Using PC3 and DU145 human prostate cancer xenograft models in mice, we confirmed that XRT induces Hsp72 release primarily from implanted tumors. In vitro studies using supernatant recovered from irradiated human prostate cancer cells point to exosomes containing Hsp72 as a possible stimulator of pro-inflammatory cytokine production and costimulatory molecules expression in human DC. Conclusions The current study confirms for the first time in an actual clinical setting elevation of circulating serum Hsp72 with XRT. The accompanying studies in mice and in vitro identify the released exosomes containing Hsp72 as playing a pivotal role in stimulating pro-inflammatory immune responses. These findings, if validated, may lead to new treatment paradigms for common human malignancies. PMID:20430459

Reduction of Serious Adverse Events Demanding Study Exclusion in Model Development: Extracorporeal Life Support Resuscitation of Ventricular Fibrillation Cardiac Arrest in Rats.

PubMed

Warenits, Alexandra-Maria; Sterz, Fritz; Schober, Andreas; Ettl, Florian; Magnet, Ingrid Anna Maria; Högler, Sandra; Teubenbacher, Ursula; Grassmann, Daniel; Wagner, Michael; Janata, Andreas; Weihs, Wolfgang

2016-12-01

Extracorporeal life support is a promising concept for selected patients in refractory cardiogenic shock and for advanced life support of persistent ventricular fibrillation cardiac arrest. Animal models of ventricular fibrillation cardiac arrest could help to investigate new treatment strategies for successful resuscitation. Associated procedural pitfalls in establishing a rat model of extracorporeal life support resuscitation need to be replaced, refined, reduced, and reported.Anesthetized male Sprague-Dawley rats (350-600 g) (n = 126) underwent cardiac arrest induced with a pacing catheter placed into the right ventricle via a jugular cannula. Rats were resuscitated with extracorporeal life support, mechanical ventilation, defibrillation, and medication. Catheter and cannula explantation was performed if restoration of spontaneous circulation was achieved. All observed serious adverse events (SAEs) occurring in each of the experimental phases were analyzed.Restoration of spontaneous circulation could be achieved in 68 of 126 rats (54%); SAEs were observed in 76 (60%) experiments. Experimental procedures related SAEs were 62 (82%) and avoidable human errors were 14 (18%). The most common serious adverse events were caused by insertion or explantation of the venous bypass cannula and resulted in lethal bleeding, cannula dislocation, or air embolism.Establishing an extracorporeal life support model in rats has confronted us with technical challenges. Even advancements in small animal critical care management over the years delivered by an experienced team and technical modifications were not able to totally avoid such serious adverse events. Replacement, refinement, and reduction reports of serious adverse events demanding study exclusions to avoid animal resources are missing and are presented hereby.

Hepatitis B virus surface antigen impairs myeloid dendritic cell function: a possible immune escape mechanism of hepatitis B virus

PubMed Central

Op den Brouw, Marjoleine L; Binda, Rekha S; van Roosmalen, Mark H; Protzer, Ulrike; Janssen, Harry L A; van der Molen, Renate G; Woltman, Andrea M

2009-01-01

Chronic hepatitis B virus (HBV) infection is the result of an inadequate immune response towards the virus. Myeloid dendritic cells (mDC) of patients with chronic HBV are impaired in their maturation and function, resulting in more tolerogenic rather than immunogenic responses, which may contribute to viral persistence. The mechanism responsible for altered mDC function remains unclear. The HBV-infected patients display large amounts of HBV particles and viral proteins in their circulation, especially the surface antigen HBsAg, which allows multiple interactions between the virus, its viral proteins and DC. To assess whether HBV directly influences mDC function, the effects of HBV and HBsAg on human mDC maturation and function were investigated in vitro. As already described for internalization of HBV by DC, the present study shows that peripheral blood-derived mDC of healthy controls also actively take up HBsAg in a time-dependent manner. Cytokine-induced maturation in the presence of HBV or HBsAg resulted in a significantly more tolerogenic mDC phenotype as demonstrated by a diminished up-regulation of costimulatory molecules and a decreased T-cell stimulatory capacity, as assessed by T-cell proliferation and interferon-γ production. In addition, the presence of HBV significantly reduced interleukin-12 production by mDC. These results show that both HBV particles and purified HBsAg have an immune modulatory capacity and may directly contribute to the dysfunction of mDC in patients with chronic HBV. The direct immune regulatory effect of HBV and circulating HBsAg particles on the function of DC can be considered as part of the mechanism by which HBV escapes immunity. PMID:18624732

Modulation of aryl hydrocarbon receptor target genes in circulating lymphocytes from dairy cows bred in a dioxin-like PCB contaminated area.

PubMed

Girolami, Flavia; Spalenza, Veronica; Carletti, Monica; Sacchi, Paola; Rasero, Roberto; Nebbia, Carlo

2013-04-15

Animal productions (i.e. fish, eggs, milk and dairy products) represent the major source of exposure to dioxins, furans, and dioxin-like (DL) polychlorobiphenyls for humans. The negative effects of these highly toxic and persistent pollutants are mediated by the activation of the aryl hydrocarbon receptor (AHR) that elicits the transcriptional induction of several genes, including those involved in xenobiotic metabolism. Previously we demonstrated the presence and functioning of the AHR signaling pathway in primary cultures of bovine blood lymphocytes. The aim of the present study was to investigate by real time PCR the expression and the inducibility of selected target genes (i.e. AHR, AHR nuclear translocator (ARNT), AHR repressor, CYP1A1 and CYP1B1) in uncultured cells from dairy cows naturally exposed to DL-compounds. The study was carried out on two groups of animals bred in a highly polluted area and characterized by a different degree of contamination, as assessed by bulk milk TEQ values, and a control group reared in an industry free area. Bovine lymphocytes expressed only AHR, ARNT and CYP1B1 genes to a detectable level; moreover, only CYP1B1 expression appeared to be correlated to TEQ values, being higher in the most contaminated group, and decreasing along with animal decontamination. Finally, lymphocytes from exposed cows displayed a lower inducibility of both CYP1A1 and CYP1B1 after the in vitro treatment with a specific AHR ligand. In conclusion, our results indicate that DL-compound contaminated cows may display significant changes in AHR-target gene expression of circulating lymphocytes. Copyright © 2013 Elsevier B.V. All rights reserved.

Emergence of a Norovirus GII.4 Strain Correlates with Changes in Evolving Blockade Epitopes

PubMed Central

Lindesmith, Lisa C.; Costantini, Verónica; Swanstrom, Jesica; Debbink, Kari; Donaldson, Eric F.; Vinjé, Jan

2013-01-01

The major capsid protein of norovirus GII.4 strains is evolving rapidly, resulting in epidemic strains with altered antigenicity. GII.4.2006 Minerva strains circulated at pandemic levels in 2006 and persisted at lower levels until 2009. In 2009, a new GII.4 variant, GII.4.2009 New Orleans, emerged and since then has become the predominant strain circulating in human populations. To determine whether changes in evolving blockade epitopes correlate with the emergence of the GII.4.2009 New Orleans strains, we compared the antibody reactivity of a panel of mouse monoclonal antibodies (MAbs) against GII.4.2006 and GII.4.2009 virus-like particles (VLPs). Both anti-GII.4.2006 and GII.4.2009 MAbs effectively differentiated the two strains by VLP-carbohydrate ligand blockade assay. Most of the GII.4.2006 MAbs preferentially blocked GII.4.2006, while all of the GII.4.2009 MAbs preferentially blocked GII.4.2009, although 8 of 12 tested blockade MAbs blocked both VLPs. Using mutant VLPs designed to alter predicted antigenic epitopes, binding of seven of the blockade MAbs was impacted by alterations in epitope A, identifying residues 294, 296, 297, 298, 368, and 372 as important antigenic sites in these strains. Convalescent-phase serum collected from a GII.4.2009 outbreak confirmed the immunodominance of epitope A, since alterations of epitope A affected serum reactivity by 40%. These data indicate that the GII.4.2009 New Orleans variant has evolved a key blockade epitope, possibly allowing for at least partial escape from protective herd immunity and provide epidemiological support for the utility of monitoring changes in epitope A in emergent strain surveillance. PMID:23269783

Response of circulating ghrelin levels to insulin therapy in children with newly diagnosed type 1 diabetes mellitus.

PubMed

Soriano-Guillén, Leandro; Barrios, Vicente; Lechuga-Sancho, Alfonso; Chowen, Julie A; Argente, Jesús

2004-05-01

Ghrelin is secreted primarily by the stomach, although other tissues such as the pancreas synthesize a minor proportion. The discovery of a new cell type that produces ghrelin in the human pancreas and that this organ expresses GHS-R opens new perspectives in the understanding of the control of glucose metabolism. We have studied 22 children with newly diagnosed type 1 diabetes mellitus at four different points: at diagnosis before insulin therapy, after 48-60 h of insulin therapy, and after 1 and 4 mo of insulin treatment. At each point circulating levels of ghrelin, leptin, IGF-I, IGF binding protein (IGFBP)-1, IGFBP-2, IGFBP-3, and glucose were determined. Ghrelin levels were significantly decreased at diagnosis (573 +/- 68 pg/mL, p < 0.01) compared with controls (867 +/- 38 pg/mL) and remained decreased after insulin therapy (d 2: 595 +/- 68 pg/mL; 1 mo: 590 +/- 61 pg/mL; 4 mo: 538 +/- 67 pg/mL) with no differences before or after insulin treatment. There was a negative correlation between ghrelin levels and body mass index at all of the study points, whereas a negative correlation between ghrelin and glucose concentrations was only observed after insulin therapy. No correlation between ghrelin and HbA1c was found at any point. A positive correlation between ghrelin and IGFBP-1 was found after insulin therapy, but no correlation with other members of the IGF system or leptin was found. In conclusion, these data could indicate a possible link between glucose concentrations and ghrelin; hence, the persisting low ghrelin levels in diabetic children may suggest a defensive mechanism against hyperglycemia.

[From the medieval hospitals hospices to modern National public Health Institutes].

PubMed

de Micheli, Alfredo

2016-01-01

Since the most ancient times, hospital constructions and progresses in the clinical practice advanced pari passu. We can find exampless of this statement in Greek regions as well as in Greek citie overseas. Thus, during the renaissance, great figures ot that time converged in Italy: The genius Leonardo da Vinci (1452-1519) and Leon Battista Alberti (1404-1472), a humanist and innovator of architecture. Michelangelo Buonarroti (1475-1564) and his contemporany artists performed anatomical dissection to perfect their art by studying the human body. Anatomical studies flourished at the University of Padua, driven by the Flemish Master. Based on the rigorous study of the anatomical substrate, the studies on the function of the already known organic structures excelled in the xvii century. That century started with the revelation of the major blood circulation by the British physician William Harvey, alumni of the University of Padua, and continued with the description of the minior or pulmonary circulation by ancient or contemporany authors and of the peripheral connections between the arterial and the venous system (Marcelo Malpighi, 1661). All these researchers, and others, were membres of the University of Padua, were the beneficial influence of the teachings of Galileo persisted. In the following centuries, together with the embryological and normal anatomy, the pathological anatomy, systematized by G.B. Morgani, became the cornerstone of the clinical practice. The model of the ancient hospitals evolved to ward the National Institutes of Health in Mexico fostered by Dr. Ignacio Chávez. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

High-risk oncogenic HPV genotype infection associates with increased immune activation and T cell exhaustion in ART-suppressed HIV-1-infected women

PubMed Central

Papasavvas, Emmanouil; Surrey, Lea F.; Glencross, Deborah K.; Azzoni, Livio; Joseph, Jocelin; Omar, Tanvier; Feldman, Michael D.; Williamson, Anna-Lise; Siminya, Maureen; Swarts, Avril; Yin, Xiangfan; Liu, Qin; Firnhaber, Cynthia; Montaner, Luis J.

2016-01-01

ABSTRACT Persistence of human papillomavirus (HPV) and cervical disease in the context of HIV co-infection can be influenced by introduction of antiretroviral therapy (ART) and sustained immune activation despite ART. We conducted a cross-sectional study in order to evaluate immune activation/exhaustion in ART-suppressed HIV+ women with or without high-risk (HR) HPV-related cervical intraepithelial neoplasia (CIN). 55 South African women were recruited in three groups: HR (-) (n = 16) and HR (+) (n = 15) HPV with negative cervical histopathology, and HR (+) HPV with CIN grade 1/2/3 (n = 24). Sampling included endocervical brushing (HPV DNA genotyping), Pap smear (cytology), colposcopic punch biopsy (histopathology, histochemical evaluation of immune cells), and peripheral blood (clinical assessment, flow cytometry-based immune subset characterization). Statistics were done using R2.5.1. Irrespective of the presence of CIN, HR (+) HPV women had higher circulating levels of T cells expressing markers of activation/exhaustion (CD38, PD1, CTLA-4, BTLA, CD160), Tregs, and myeloid subsets expressing corresponding ligands (PDL1, PDL2, CD86, CD40, HVEM) than HR (-) HPV women. A decrease in circulating NK cells was associated with CIN grade. CD4+ T cell count associated negatively with T cell exhaustion and expression of negative regulators on myeloid cells. Women with CIN when compared to HR (-) HPV women, had higher cervical cell density in stroma and epithelium for CD4+, CD68+, and CD11c+ cells, and only in stroma for CD8+ cells. We conclude that in ART-suppressed HIV-infected women with HPV co-infection the levels of T and myeloid cell activation/exhaustion are associated with the presence of HR HPV genotypes. PMID:27467943

Evolution of a reassortant North American gull influenza virus lineage: drift, shift and stability

USGS Publications Warehouse

Hall, Jeffrey S.; TeSlaa, Joshua L.; Nashold, Sean W.; Halpin, Rebecca A.; Stockwell, Timothy; Wentworth, David E.; Dugan, Vivien; Ip, Hon S.

2013-01-01

Background: The role of gulls in the ecology of avian influenza (AI) is different than that of waterfowl. Different constellations of subtypes circulate within the two groups of birds and AI viruses isolated from North American gulls frequently possess reassortant genomes with genetic elements from both North America and Eurasian lineages. A 2008 isolate from a Newfoundland Great Black-backed Gull contained a mix of North American waterfowl, North American gull and Eurasian lineage genes. Methods: We isolated, sequenced and phylogenetically compared avian influenza viruses from 2009 Canadian wild birds. Results: We analyzed six 2009 virus isolates from Canada and found the same phylogenetic lineage had persisted over a larger geographic area, with an expanded host range that included dabbling and diving ducks as well as gulls. All of the 2009 virus isolates contained an internal protein coding set of genes of the same Eurasian lineage genes except PB1 that was from a North American lineage, and these genes continued to evolve by genetic drift. We show evidence that the 2008 Great Black-backed Gull virus was derived from this lineage with a reassortment of a North American PA gene into the more stable core set of internal protein coding genes that has circulated in avian populations for at least 2 years. From this core, the surface glycoprotein genes have switched several times creating H13N6, H13N2, and H16N3 subtypes. These gene segments were from North American lineages except for the H16 and N3 vRNAs. Conclusions: This process appears similar to genetic shifts seen with swine influenza where a stable "triple reassortant internal gene" core has circulated in swine populations with genetic shifts occurring with hemaggluttinin and neuraminidase proteins getting periodically switched. Thus gulls may serve as genetic mixing vessels for different lineages of avian influenza, similar to the role of swine with regards to human influenza. These findings illustrate the need for continued surveillance in gull and waterfowl populations, both on the Pacific and especially Atlantic coasts of North America, to document virus intercontinental movement and the role of gull species in the evolution and epidemiology of AI.

Effect of Increased Blood Flow on Pulmonary Circulation Before and During High Altitude Acclimatization.

PubMed

Hilty, Matthias Peter; Müller, Andrea; Flück, Daniela; Siebenmann, Christoph; Rasmussen, Peter; Keiser, Stefanie; Auinger, Katja; Lundby, Carsten; Maggiorini, Marco

2016-12-01

Matthias Peter Hilty, Andrea Mueller, Daniela Flück, Christoph Siebenmann, Peter Rasmussen, Stefanie Keiser, Katja Auinger, Carsten Lundby, and Marco Maggiorini. Effect of increased blood flow on the pulmonary circulation before and during high altitude acclimatization. High Alt Med Biol. 17:305-314, 2016.-Introduction and Methods: Acute exposure to high altitude increases pulmonary artery pressure (Ppa) and pulmonary vascular resistance (PVR). The evolution of Ppa and PVR with continuous hypoxic exposure remains, however, elusive. To test the hypothesis that altitude exposure leads to a persistent elevation in Ppa and PVR throughout acclimatization in seven healthy male subjects, echocardiography was performed at sea level (SL; 488 m) weekly during a 4-week sojourn at 3454 m (HA1-HA4) and upon return (SL2). Pulmonary artery catheterization and bilateral thigh cuff release maneuver were performed at SL and HA3 to study the properties of pulmonary circulation after 3 weeks of acclimatization. Pulmonary artery catheter determined that systolic Ppa (mean ± SEM) was increased from 20 ± 1 at SL to 27 ± 2 mmHg at HA3 (p < 0.01). Echocardiography assessed that systolic Ppa remained equally increased throughout acclimatization (26 ± 2, 25 ± 2, 25 ± 2, and 24 ± 2 mmHg at HA1-HA4; p = 0.93) and returned to baseline upon return (17 ± 2, 18 ± 1 mmHg at SL, SL2; p = 0.3). The same was shown for PVR. Right heart function remained unaffected. Thigh cuff release maneuvers at SL and HA3 resulted in similar increase in cardiac output (2.5 ± 0.5 and 2.2 ± 0.4 L/min; p = 0.61) without affecting mean Ppa. Prolonged altitude exposure leads to a persistent increase in Ppa and PVR without affecting right heart function and is fully reversible within 1 week after return to SL. The thigh cuff release maneuver-induced increase in cardiac output suggests a preserved ability of pulmonary circulation to cope with sudden remarkable increase in pulmonary blood flow throughout acclimatization.

Prolonged Exposure of Primary Human Muscle Cells to Plasma Fatty Acids Associated with Obese Phenotype Induces Persistent Suppression of Muscle Mitochondrial ATP Synthase β Subunit

PubMed Central

Tran, Lee; Hanavan, Paul D.; Campbell, Latoya E.; De Filippis, Elena; Lake, Douglas F.; Coletta, Dawn K.; Roust, Lori R.; Mandarino, Lawrence J.; Carroll, Chad C.; Katsanos, Christos S.

2016-01-01

Our previous studies show reduced abundance of the β-subunit of mitochondrial H+-ATP synthase (β-F1-ATPase) in skeletal muscle of obese individuals. The β-F1-ATPase forms the catalytic core of the ATP synthase, and it is critical for ATP production in muscle. The mechanism(s) impairing β-F1-ATPase metabolism in obesity, however, are not completely understood. First, we studied total muscle protein synthesis and the translation efficiency of β-F1-ATPase in obese (BMI, 36±1 kg/m2) and lean (BMI, 22±1 kg/m2) subjects. Both total protein synthesis (0.044±0.006 vs 0.066±0.006%·h-1) and translation efficiency of β-F1-ATPase (0.0031±0.0007 vs 0.0073±0.0004) were lower in muscle from the obese subjects when compared to the lean controls (P<0.05). We then evaluated these same responses in a primary cell culture model, and tested the specific hypothesis that circulating non-esterified fatty acids (NEFA) in obesity play a role in the responses observed in humans. The findings on total protein synthesis and translation efficiency of β-F1-ATPase in primary myotubes cultured from a lean subject, and after exposure to NEFA extracted from serum of an obese subject, were similar to those obtained in humans. Among candidate microRNAs (i.e., non-coding RNAs regulating gene expression), we identified miR-127-5p in preventing the production of β-F1-ATPase. Muscle expression of miR-127-5p negatively correlated with β-F1-ATPase protein translation efficiency in humans (r = – 0.6744; P<0.01), and could be modeled in vitro by prolonged exposure of primary myotubes derived from the lean subject to NEFA extracted from the obese subject. On the other hand, locked nucleic acid inhibitor synthesized to target miR-127-5p significantly increased β-F1-ATPase translation efficiency in myotubes (0.6±0.1 vs 1.3±0.3, in control vs exposure to 50 nM inhibitor; P<0.05). Our experiments implicate circulating NEFA in obesity in suppressing muscle protein metabolism, and establish impaired β-F1-ATPase translation as an important consequence of obesity. PMID:27532680

Emergence and Evolution of Novel Reassortant Influenza A Viruses in Canines in Southern China.

PubMed

Chen, Ying; Trovão, Nídia S; Wang, Guojun; Zhao, Weifeng; He, Ping; Zhou, Huabo; Mo, Yanning; Wei, Zuzhang; Ouyang, Kang; Huang, Weijian; García-Sastre, Adolfo; Nelson, Martha I

2018-06-05

The capacity of influenza A viruses (IAVs) to host jump from animal reservoir species to humans presents an ongoing pandemic threat. Birds and swine are considered major reservoirs of viral genetic diversity, whereas equines and canines have historically been restricted to one or two stable IAV lineages with no transmission to humans. Here, by sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to 2015, we demonstrate that the evolution of canine influenza viruses (CIVs) in Asian dogs is increasingly complex, presenting a potential threat to humans. First, two reassortant H1N1 virus genotypes were introduced independently from swine into canines in Guangxi, including one genotype associated with a zoonotic infection. The genomes contain segments from three lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1. Furthermore, the swine-origin H1N1 viruses have transmitted onward in canines and reassorted with the CIV-H3N2 viruses that circulate endemically in Asian dogs, producing three novel reassortant CIV genotypes (H1N1r, H1N2r, and H3N2r [r stands for reassortant]). CIVs from this study were collected primarily from pet dogs presenting with respiratory symptoms at veterinary clinics, but dogs in Guangxi are also raised for meat, and street dogs roam freely, creating a more complex ecosystem for CIV transmission. Further surveillance is greatly needed to understand the full genetic diversity of CIV in southern China, the nature of viral emergence and persistence in the region's diverse canine populations, and the zoonotic risk as the viruses continue to evolve. IMPORTANCE Mammals have emerged as critically underrecognized sources of influenza virus diversity, including pigs that were the source of the 2009 pandemic and bats and bovines that harbor highly divergent viral lineages. Here, we identify two reassortant IAVs that recently host switched from swine to canines in southern China, including one virus with known zoonotic potential. Three additional genotypes were generated via reassortment events in canine hosts, demonstrating the capacity of dogs to serve as "mixing vessels." The continued expansion of IAV diversity in canines with high human contact rates requires enhanced surveillance and ongoing evaluation of emerging pandemic threats. Copyright © 2018 Chen et al.

Developmental programming: prenatal steroid excess disrupts key members of intraovarian steroidogenic pathway in sheep.

PubMed

Padmanabhan, Vasantha; Salvetti, Natalia R; Matiller, Valentina; Ortega, Hugo H

2014-09-01

Prenatal testosterone (T) excess disrupts ovarian cyclicity and increases circulating estradiol levels as well as follicular recruitment and persistence culminating in multifollicular ovary similar to women with polycystic ovary syndrome. We tested whether prenatal T excess, by androgenic or estrogenic action, disrupts the steroid biosynthetic machinery in sheep in a cell-, follicle stage-, age-, and treatment-specific manner consistent with the ovarian disruptions and increased estradiol release. Impact of T/dihydrotestosterone (DHT) treatments from days 30-90 of gestation on steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase, cytochrome P-450 17α-hydroxylase/C17, 20-lyase (CYP17A1), and cytochrome P-450 aromatase (CYP19A1) were examined on fetal day 90, 140 and 10 months (postpubertal), and 21 months (adult, no DHT group) of age by immunohistochemistry. All 4 markers changed in a cell-, follicle stage-, and age-specific manner. Both treatments increased steroidogenic acute regulatory protein expression in preantral follicles of postpubertal and adult females. Effects of prenatal T and DHT on 3β-hydroxysteroid dehydrogenase differed in a follicle- and age-specific manner. CYP17A1 was reduced in the theca interna of antral follicles by T, but not DHT, in 10- and 21-month-old females. CYP19A1 was reduced by both T and DHT at all ages barring an increase on fetal day 140. Reduced granulosa CYP19A1 and thecal CYP17A1 in adults likely disrupt the intrafollicular androgen/estrogen balance contributing to follicular persistence. The reduced thecal CYP17A1 expression suggests that the hyperandrogenic ovarian phenotype may originate from increased enzyme activity or alternatively via a different isoform of CYP17. The reduced CYP19A1 in antral follicles of adults indicates that the increased circulating estradiol release likely arises from the increased number of persisting follicles.

Mesoscale and Synoptic Summertime Circulations and Their Impact on Visibility in the Arabian Gulf

NASA Astrophysics Data System (ADS)

Eleuterio, D. P.; Walker, A. L.

2005-12-01

Although frequently characterized as a region of relatively persistent northwesterly winds, often referred to as the 40-day shamal, several researchers have recognized significant temporal and spatial variability in the summer low level winds in the Arabian Gulf. In addition to the synoptically driven gradient between the subtropical high to the north and the monsoon trough across the Gulf of Oman and Northern Arabian Sea, there are complex interactions between the Saudi Arabian and Pakistani heat lows, land-sea breeze circulations, and coastal terrain influence due to the proximity of the Zagros Mountains. These interactions frequently result in several distinct wind regimes within the Arabian Gulf, to include weak thermally and dynamically forced southerlies in the southern Gulf, a diurnally varying region of convergence/ divergence across the central Gulf, and northwesterly shamal type flow in the northern Gulf. The relative orientation and strength of these wind regimes and the strength of the subsidence inversion at the top of the marine boundary layer greatly impact the aerosol loading over water and resulting visibility due to wind-blown sand, dust, and smoke. Several case studies are examined to explore the interaction between mesoscale and synoptic forcing and the resulting spatial and temporal variability in visibility and aerosol optical depth. Conditions range from two to three day periods of rapid and persistent regional clearing with freshening northwesterly winds, to persistent periods of moderate to poor visibility in marine haze under light winds, to large scale events that create a distinct wind and dust front, severely reducing visibility through much of Iraq, Kuwait, and Saudi Arabia, and extending well into the Arabian Gulf. These strong, widespread events may be correlated with synoptically forced conditions farther north. Alternatively, smaller scale regional plumes of mobilized dust are often created by mesoscale events which, in conjunction with oil smoke and industrial pollution, can rapidly reduce visibility in localized regions for periods of 1-2 days and are relatively difficult to forecast because of their mesoscale nature.

Lactase non-persistence is directed by DNA variation-dependent epigenetic aging

PubMed Central

Labrie, Viviane; Buske, Orion J; Oh, Edward; Jeremian, Richie; Ptak, Carolyn; Gasiūnas, Giedrius; Maleckas, Almantas; Petereit, Rūta; Žvirbliene, Aida; Adamonis, Kęstutis; Kriukienė, Edita; Koncevičius, Karolis; Gordevičius, Juozas; Nair, Akhil; Zhang, Aiping; Ebrahimi, Sasha; Oh, Gabriel; Šikšnys, Virginijus; Kupčinskas, Limas; Brudno, Michael; Petronis, Arturas

2016-01-01

Inability to digest lactose due to lactase non-persistence is a common trait in adult mammals, with the exception of certain human populations that exhibit lactase persistence. It is not clear how the lactase gene can be dramatically downregulated with age in most individuals, but remains active in some. We performed a comprehensive epigenetic study of the human and mouse intestine using chromosome-wide DNA modification profiling and targeted bisulfite sequencing. Epigenetically-controlled regulatory elements were found to account for the differences in lactase mRNA levels between individuals, intestinal cell types and species. The importance of these regulatory elements in modulating lactase mRNA levels was confirmed by CRISPR-Cas9-induced deletions. Genetic factors contribute to epigenetic changes occurring with age at the regulatory elements, as lactase persistence- and non-persistence-DNA haplotypes demonstrated markedly different epigenetic aging. Thus, genetic factors facilitate a gradual accumulation of epigenetic changes with age to affect phenotypic outcome. PMID:27159559

Money circulation networks reveal emerging geographical communities

NASA Astrophysics Data System (ADS)

Brockmann, D.; Theis, F.; David, V.

2008-03-01

Geographical communities and their boundaries are key determinants of various spatially extended dynamical phenomena. Examples are migration dynamics of species, the spread of infectious diseases, bioinvasive processes, and the spatial evolution of language. We address the question to what extend multiscale human transportation networks encode geographical community structures, how they differ from geopolitical classifications, whether they are spatially coherent, and analyse their structure as a function of length scale. Our analysis is based on a proxy network for human transportation obtained from the geographic circulation of more than 10 million dollar bills in the United States recorded at the bill tracking website www.wheresgeorge.com. The data extends that of a previous study (Brockmann et al., Nature 2006) on the discovery of scaling laws of human travel by an order of magnitude and permits an approach to multiscale human transportation from a network perspective.

MiR-422a as a Potential Cellular MicroRNA Biomarker for Postmenopausal Osteoporosis

PubMed Central

Cao, Zheng; Moore, Benjamin T.; Wang, Yang; Peng, Xian-Hao; Lappe, Joan M.; Recker, Robert R.; Xiao, Peng

2014-01-01

Background MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that regulate gene expression by targeting mRNAs. Recently, miRNAs have been shown to play important roles in the etiology of various diseases. However, little is known about their roles in the development of osteoporosis. Circulating monocytes are osteoclast precursors that also produce various factors important for osteoclastogenesis. Previously, we have identified a potential biomarker miR-133a in circulating monocytes for postmenopausal osteoporosis. In this study, we aimed to further identify significant miRNA biomarkers in human circulating monocytes underlying postmenopausal osteoporosis. Methodology/Principal Findings We used ABI TaqMan miRNA array followed by qRT-PCR validation in human circulating monocytes from 10 high BMD and 10 low BMD postmenopausal Caucasian women to identify miRNA biomarkers. MiR-422a was up-regulated with marginal significance (P = 0.065) in the low compared with the high BMD group in the array analysis. However, a significant up-regulation of miR-422a was identified in the low BMD group by qRT-PCR analysis (P = 0.029). We also performed bioinformatic target gene analysis and found several potential target genes of miR-422a which are involved in osteoclastogenesis. Further qRT-PCR analyses of the target genes in the same study subjects showed that the expression of five of these genes (CBL, CD226, IGF1, PAG1, and TOB2) correlated negatively with miR-422a expression. Conclusions/Significance Our study suggests that miR-422a in human circulating monocytes (osteoclast precursors) is a potential miRNA biomarker underlying postmenopausal osteoporosis. PMID:24820117

MiR-422a as a potential cellular microRNA biomarker for postmenopausal osteoporosis.

PubMed

Cao, Zheng; Moore, Benjamin T; Wang, Yang; Peng, Xian-Hao; Lappe, Joan M; Recker, Robert R; Xiao, Peng

2014-01-01

MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that regulate gene expression by targeting mRNAs. Recently, miRNAs have been shown to play important roles in the etiology of various diseases. However, little is known about their roles in the development of osteoporosis. Circulating monocytes are osteoclast precursors that also produce various factors important for osteoclastogenesis. Previously, we have identified a potential biomarker miR-133a in circulating monocytes for postmenopausal osteoporosis. In this study, we aimed to further identify significant miRNA biomarkers in human circulating monocytes underlying postmenopausal osteoporosis. We used ABI TaqMan miRNA array followed by qRT-PCR validation in human circulating monocytes from 10 high BMD and 10 low BMD postmenopausal Caucasian women to identify miRNA biomarkers. MiR-422a was up-regulated with marginal significance (P = 0.065) in the low compared with the high BMD group in the array analysis. However, a significant up-regulation of miR-422a was identified in the low BMD group by qRT-PCR analysis (P = 0.029). We also performed bioinformatic target gene analysis and found several potential target genes of miR-422a which are involved in osteoclastogenesis. Further qRT-PCR analyses of the target genes in the same study subjects showed that the expression of five of these genes (CBL, CD226, IGF1, PAG1, and TOB2) correlated negatively with miR-422a expression. Our study suggests that miR-422a in human circulating monocytes (osteoclast precursors) is a potential miRNA biomarker underlying postmenopausal osteoporosis.

The Effects of Learning Styles and Meaningful Learning on the Learning Achievement of Gamification Health Education Curriculum

ERIC Educational Resources Information Center

Fan, Kuo-Kuang; Xiao, Peng-wei; Su, Chung-Ho

2015-01-01

This study aims to discuss the correlations among learning styles, meaningful learning, and learning achievement. Directed at the rather difficult to comprehend human blood circulation unit in the biology materials for junior high school students, a Mobile Meaningful Blood Circulation Learning System, called MMBCLS gamification learning, was…

Enhanced virulence of clade 2.3.2.1 highly pathogenic avian influenza A(H5N1) viruses in ferrets

USDA-ARS?s Scientific Manuscript database

Sporadic avian to human transmission of highly pathogenic avian influenza (HPAI) A (H5N1) viruses necessitates the analysis of currently circulating and evolving clades to assess their potential risk. Following the spread and sustained circulation of clade 2 viruses across multiple continents, num...

Persistence of West Nile virus.

PubMed

Garcia, Melissa N; Hasbun, Rodrigo; Murray, Kristy O

2015-02-01

West Nile virus (WNV) is a widespread global pathogen that results in significant morbidity and mortality. Data from animal models provide evidence of persistent renal and neurological infection from WNV; however, the possibility of persistent infection in humans and long-term neurological and renal outcomes related to viral persistence remain largely unknown. In this paper, we provide a review of the literature related to persistent infection in parallel with the findings from cohorts of patients with a history of WNV infection. The next steps for enhancing our understanding of WNV as a persistent pathogen are discussed. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Mutation in West Nile Virus Structural Protein prM during Human Infection.

PubMed

Lustig, Yaniv; Lanciotti, Robert S; Hindiyeh, Musa; Keller, Nathan; Milo, Ron; Mayan, Shlomo; Mendelson, Ella

2016-09-01

A mutation leading to substitution of a key amino acid in the prM protein of West Nile virus (WNV) occurred during persistent infection of an immunocompetent patient. WNV RNA persisted in the patient's urine and serum in the presence of low-level neutralizing antibodies. This case demonstrates active replication of WNV during persistent infection.

Representations of the Stratospheric Polar Vortices in Versions 1 and 2 of the Goddard Earth Observing System Chemistry-Climate Model (GEOS CCM)

NASA Technical Reports Server (NTRS)

Pawson, S.; Stolarski, R.S.; Nielsen, J.E.; Perlwitz, J.; Oman, L.; Waugh, D.

2009-01-01

This study will document the behavior of the polar vortices in two versions of the GEOS CCM. Both versions of the model include the same stratospheric chemistry, They differ in the underlying circulation model. Version 1 of the GEOS CCM is based on the Goddard Earth Observing System, Version 4, general circulation model which includes the finite-volume (Lin-Rood) dynamical core and physical parameterizations from Community Climate Model, Version 3. GEOS CCM Version 2 is based on the GEOS-5 GCM that includes a different tropospheric physics package. Baseline simulations of both models, performed at two-degree spatial resolution, show some improvements in Version 2, but also some degradation, In the Antarctic, both models show an over-persistent stratospheric polar vortex with late breakdown, but the year-to-year variations that are overestimated in Version I are more realistic in Version 2. The implications of this for the interactions with tropospheric climate, the Southern Annular Mode, will be discussed. In the Arctic both model versions show a dominant dynamically forced variabi;ity, but Version 2 has a persistent warm bias in the low stratosphere and there are seasonal differences in the simulations. These differences will be quantified in terms of climate change and ozone loss. Impacts of model resolution, using simulations at one-degree and half-degree, and changes in physical parameterizations (especially the gravity wave drag) will be discussed.

Spatial stabilization and intensification of moistening and drying rate patterns under future climate change

NASA Astrophysics Data System (ADS)

Chavaillaz, Y.; Joussaume, S.; Bony, S.; Braconnot, P.

2015-12-01

Most climate studies characterize the future climate change by considering the evolution between a fixed current baseline and the future. It emphasizes an increase of future precipitation changes with global warming. Here we use an alternative approach that considers rate of change indicators related to precipitation using projections of an ensemble of General Circulation Models. The rate is defined by the difference between two subsequent 20-year periods. This approach can be relevant to impacts affecting upcoming generations, and to their continuous adaptation towards a changing target. Under the strongest emission pathway (RCP8.5), moistening and drying rates strongly increase at the global scale. As we move further over the twenty-first century, more and more regions exhibit substantial rates. These regions are modified over time due to spatial variability of precipitation. However, we show that they tend to become more geographically stationary through the century, leading to persisting trends at several places over the globe. Whilst global warming is accelerating, this spatial stabilization is due to the decreasing relative influence of global circulation in precipitation changes compared to thermodynamic processes. In specific regions, the combination of intensification and persistence of such substantial rates should be considered in the framework of future impact studies (i.e. the Mediterranean Sea, Central America, South Asia and the Arctic). These trends are already visible in the current period, but could almost disappear if strong mitigation policies (RCP2.6) were quickly implemented.

Longitudinal expression of Toll-like receptors on dendritic cells in uncomplicated pregnancy and postpartum

PubMed Central

Young, Brett C.; Stanic, Aleksandar K.; Panda, Britta; Rueda, Bo R.; Panda, Alexander

2014-01-01

OBJECTIVE Toll-like receptors (TLRs) are integral parts of the innate immune system and have been implicated in complications of pregnancy. The longitudinal expression of TLRs on dendritic cells in the maternal circulation during uncomplicated pregnancies is unknown. The objective of this study was to prospectively evaluate TLRs 1-9 as expressed on dendritic cells in the maternal circulation at defined intervals throughout pregnancy and postpartum. STUDY DESIGN This was a prospective cohort of 30 pregnant women with uncomplicated pregnancies and 30 nonpregnant controls. TLRs and cytokine expression was measured in unstimulated dendritic cells at 4 defined intervals during pregnancy and postpartum. Basal expression of TLRs and cytokines was measured by multicolor flow cytometry. The percent-positive dendritic cells for each TLRs were compared with both nonpregnant and postpartum levels with multivariate linear regression. RESULTS TLRs 1, 7, and 9 were elevated compared with nonpregnant controls with persistent elevation of TLR 1 and interleukin-12 (IL-12) into the postpartum period. Concordantly, levels of IL-6, IL-12, interferon alpha, and tumor necrosis factor alpha increased during pregnancy and returned to levels similar to nonpregnant controls during the postpartum period. The elevated levels of TLR 1 and IL-12 were persistent postpartum, challenging notions that immunologic changes during pregnancy resolve after the prototypical postpartum period. CONCLUSION Normal pregnancy is associated with time-dependent changes in TLR expression compared with nonpregnant controls; these findings may help elucidate immunologic dysfunction in complicated pregnancies. PMID:24291497

Synergistic role of HSP90α and HSP90β to promote myofibroblast persistence in lung fibrosis.

PubMed

Bellaye, Pierre-Simon; Shimbori, Chiko; Yanagihara, Toyoshi; Carlson, David A; Hughes, Philip; Upagupta, Chandak; Sato, Seidai; Wheildon, Nolan; Haystead, Timothy; Ask, Kjetil; Kolb, Martin

2018-02-01

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of the lung parenchyma, causing significant morbidity through worsening dyspnoea and overall functional decline. IPF is characterised by apoptosis-resistant myofibroblasts, which are a major source for the excessive production of extracellular matrix (ECM) overtaking normal lung tissue. We sought to study the role of heat shock protein (HSP) isoforms HSP90α and HSP90β, whose distinct roles in lung fibrogenesis remain elusive.We determined the level of circulating HSP90α in IPF patients (n=31) and age-matched healthy controls (n=9) by ELISA. The release of HSP90α and HSP90β was evaluated in vitro in primary IPF and control lung fibroblasts and ex vivo after mechanical stretch on fibrotic lung slices from rats receiving adenovector-mediated transforming growth factor-β1.We demonstrate that circulating HSP90α is upregulated in IPF patients in correlation with disease severity. The release of HSP90α is enhanced by the increase in mechanical stress of the fibrotic ECM. This increase in extracellular HSP90α signals through low-density lipoprotein receptor-related protein 1 (LRP1) to promote myofibroblast differentiation and persistence. In parallel, we demonstrate that the intracellular form of HSP90β stabilises LRP1, thus amplifying HSP90α extracellular action.We believe that the specific inhibition of extracellular HSP90α is a promising therapeutic strategy to reduce pro-fibrotic signalling in IPF. Copyright ©ERS 2018.

Increasing persistent haze in Beijing: potential impacts of weakening East Asian winter monsoons associated with northwestern Pacific sea surface temperature trends

NASA Astrophysics Data System (ADS)

Pei, Lin; Yan, Zhongwei; Sun, Zhaobin; Miao, Shiguang; Yao, Yao

2018-03-01

Over the past decades, Beijing, the capital city of China, has encountered increasingly frequent persistent haze events (PHE). While the increased pollutant emissions are considered as the most important reason, changes in regional atmospheric circulations associated with large-scale climate warming also play a role. In this study, we find a significant positive trend of PHE in Beijing for the winters from 1980 to 2016 based on updated daily observations. This trend is closely related to an increasing frequency of extreme anomalous southerly episodes in North China, a weakened East Asian trough in the mid-troposphere and a northward shift of the East Asian jet stream in the upper troposphere. These conditions together depict a weakened East Asian winter monsoon (EAWM) system, which is then found to be associated with an anomalous warm, high-pressure system in the middle-lower troposphere over the northwestern Pacific. A practical EAWM index is defined as the seasonal meridional wind anomaly at 850 hPa in winter over North China. Over the period 1900-2016, this EAWM index is positively correlated with the sea surface temperature anomalies over the northwestern Pacific, which indicates a wavy positive trend, with an enhanced positive phase since the mid-1980s. Our results suggest an observation-based mechanism linking the increase in PHE in Beijing with large-scale climatic warming through changes in the typical regional atmospheric circulation.

A Functional Perspective on the Embryology and Anatomy of the Cerebral Blood Supply

PubMed Central

Menshawi, Khaled; Mohr, Jay P

2015-01-01

The anatomy of the arterial system supplying blood to the brain can influence the development of arterial disease such as aneurysms, dolichoectasia and atherosclerosis. As the arteries supplying blood to the brain develop during embryogenesis, variation in their anatomy may occur and this variation may influence the development of arterial disease. Angiogenesis, which occurs mainly by sprouting of parent arteries, is the first stage at which variations can occur. At day 24 of embryological life, the internal carotid artery is the first artery to form and it provides all the blood required by the primitive brain. As the occipital region, brain stem and cerebellum enlarge; the internal carotid supply becomes insufficient, triggering the development of the posterior circulation. At this stage, the posterior circulation consists of a primitive mesh of arterial networks that originate from projection of penetrators from the distal carotid artery and more proximally from carotid-vertebrobasilar anastomoses. These anastomoses regress when the basilar artery and the vertebral arteries become independent from the internal carotid artery, but their persistence is not uncommon in adults (e.g., persistent trigeminal artery). Other common remnants of embryological development include fenestration or duplication (most commonly of the basilar artery), hypoplasia (typically of the posterior communicating artery) or agenesis (typically of the anterior communicating artery). Learning more about the hemodynamic consequence that these variants may have on the brain territories they supply may help understand better the underlying physiopathology of cerebral arterial remodeling and stroke in patients with these variants. PMID:26060802

Transport of airborne pollen into the city of Thessaloniki: the effects of wind direction, speed and persistence

NASA Astrophysics Data System (ADS)

Damialis, Athanasios; Gioulekas, Dimitrios; Lazopoulou, Chariklia; Balafoutis, Christos; Vokou, Despina

2005-01-01

We examined the effect of the wind vector analyzed into its three components (direction, speed and persistence), on the circulation of pollen from differe nt plant taxa prominent in the Thessaloniki area for a 4-year period (1996- 1999). These plant taxa were Ambrosia spp., Artemisia spp., Chenopodiaceae, spp., Cupressaceae, Olea europaea, Pinaceae, Platanus spp., Poaceae, Populus spp., Quercus spp., and Urticaceae. Airborne pollen of Cupressaceae, Urticaceae, Quercus spp. and O. europaea make up approximately 70% of the total average annual pollen counts. The set of data that we worked with represented days without precipitation and time intervals during which winds blew from the same direction for at least 4 consecutive hours. We did this in order to study the effect of the different wind components independently of precipitation, and to avoid secondary effects produced by pollen resuspension phenomena. Factorial regression analysis among the summed bi-hourly pollen counts for each taxon and the values of wind speed and persistence per wind direction gave significant results in 22 cases (combinations of plant taxa and wind directions). The pollen concentrations of all taxa correlated significantly with at least one of the three wind components. In seven out of the 22 taxon-wind direction combinations, the pollen counts correlated positively with wind persistence, whereas this was the case for only two of the taxon-wind speed combinations. In seven cases, pollen counts correlated with the interaction effect of wind speed and persistence. This shows the importance of wind persistence in pollen transport, particularly when weak winds prevail for a considerable part of the year, as is the case for Thessaloniki. Medium/long-distance pollen transport was evidenced for Olea (NW, SW directions), Corylus (NW, SW), Poaceae (SW) and Populus (NW).

Adhesion of Lactobacillus iners AB-1 to human fibronectin: a key mediator for persistence in the vagina?

PubMed

McMillan, Amy; Macklaim, Jean M; Burton, Jeremy P; Reid, Gregor

2013-07-01

Lactobacillus iners is prominent in the human vagina and is able to persist despite development of bacterial vaginosis and treatment with antibiotics. A probable factor in its persistent survival is its ability to be retained in the vaginal epithelia. Genome sequencing of the strain showed an organism deplete of many metabolic pathways, yet equipped with fibronectin (Fn)-binding adhesins. The objective of the present study was to assess the ability of L iners AB-1 to bind immobilized Fn. Results showed that the organism superiorly bound the protein compared to other species of Lactobacillus and known binders such as Staphylococcus aureus. Treatment of L iners cells by protease rendered its binding abilities to Fn nonfunctional. The findings indicate a mechanism of vaginal persistence for a Lactobacillus species, with implications for reproductive health.

Detection of BVDV persistently infected animals in Belgium: evaluation of the strategy implemented.

PubMed

Letellier, C; De Meulemeester, L; Lomba, M; Mijten, E; Kerkhofs, P

2005-11-15

Until now, no official bovine virus diarrhea virus (BVDV) control program has been implemented in Belgium. The only legislation dealing with the detection of BVDV-infected animals concerns the purchase of animals. A strategy of control, based on the identification and elimination of persistently infected (PI) animals and the vaccination of cows before insemination has been designed in both the Northern and the Southern part of the country. The strategy of detection of PI animals relies on PCR testing of pools of blood. Individual blood samples corresponding to the positive pools are then tested by BVDV-antigen ELISA. A first evaluation of the measures already applied in Belgium is presented. Data obtained in 2003 are presented and discussed regarding the validation of the laboratory strategy, the prevalence of positive herds, the genotype of circulating viruses, the outcome of antigen positive animals and the need for improvement of the current legislation.

Outcome Prediction of Treatment of Graves' Hyperthyroidism with Antithyroid Drugs.

PubMed

Piantanida, E; Lai, A; Sassi, L; Gallo, D; Spreafico, E; Tanda, M L; Bartalena, L

2015-09-01

Graves' disease is the most common cause of hyperthyroidism in iodine-replete areas and is ultimately due to antibodies interacting with the TSH receptor on thyroid follicular cells [TSH-receptor antibody (TRAb)]. Antithyroid drugs (ATDs) belonging to the family of thionamides are the first-line treatment in Europe. ATD treatment is commonly continued for 18-24 months. Its major limitation is the high rate of relapses after drug withdrawal. Factors particularly bound to subsequent relapses are the large thyroid volume, smoking habit, persistence of TRAb in the circulation at the end of treatment, and the post-partum period. Under these conditions, consideration should be given to a definitive therapy for hyperthyroidism (radioiodine treatment, thyroidectomy), particularly if the patient is at risk of cardiovascular complications that might be exacerbated by persistence or recurrence of hyperthyroidism. © Georg Thieme Verlag KG Stuttgart · New York.

Persisting arthralgia due to Mayaro virus infection in a traveler from Brazil: is there a risk for attendants to the 2014 FIFA World Cup?

PubMed

Slegers, C A D; Keuter, M; Günther, S; Schmidt-Chanasit, J; van der Ven, A J; de Mast, Q

2014-07-01

The 2014 FIFA World Cup and the 2016 Olympic Games will attract large groups of visitors to Brazil. These visitors will be at risk for different arboviral infections, some of which not well known outside endemic areas. We report a case of a 52-year-old Dutch woman who presented with persistent arthralgia due to a Mayaro virus (MAYV) infection which she contracted in the Amazon basin in Brazil. MAYV is a mosquito-borne alphavirus which primarily circulates in humid tropical forests of South America. Infections are rarely reported in travelers and are characterized by an acute febrile illness which is often followed by a prolonged and sometimes incapacitating polyarthralgia. Both travelers and physicians should be aware of the risk of these arboviral infections and the importance of mosquito bite prevention should be stressed. Copyright © 2014 Elsevier B.V. All rights reserved.

Strong and deep Atlantic meridional overturning circulation during the last glacial cycle.

PubMed

Böhm, E; Lippold, J; Gutjahr, M; Frank, M; Blaser, P; Antz, B; Fohlmeister, J; Frank, N; Andersen, M B; Deininger, M

2015-01-01

Extreme, abrupt Northern Hemisphere climate oscillations during the last glacial cycle (140,000 years ago to present) were modulated by changes in ocean circulation and atmospheric forcing. However, the variability of the Atlantic meridional overturning circulation (AMOC), which has a role in controlling heat transport from low to high latitudes and in ocean CO2 storage, is still poorly constrained beyond the Last Glacial Maximum. Here we show that a deep and vigorous overturning circulation mode has persisted for most of the last glacial cycle, dominating ocean circulation in the Atlantic, whereas a shallower glacial mode with southern-sourced waters filling the deep western North Atlantic prevailed during glacial maxima. Our results are based on a reconstruction of both the strength and the direction of the AMOC during the last glacial cycle from a highly resolved marine sedimentary record in the deep western North Atlantic. Parallel measurements of two independent chemical water tracers (the isotope ratios of (231)Pa/(230)Th and (143)Nd/(144)Nd), which are not directly affected by changes in the global cycle, reveal consistent responses of the AMOC during the last two glacial terminations. Any significant deviations from this configuration, resulting in slowdowns of the AMOC, were restricted to centennial-scale excursions during catastrophic iceberg discharges of the Heinrich stadials. Severe and multicentennial weakening of North Atlantic Deep Water formation occurred only during Heinrich stadials close to glacial maxima with increased ice coverage, probably as a result of increased fresh-water input. In contrast, the AMOC was relatively insensitive to submillennial meltwater pulses during warmer climate states, and an active AMOC prevailed during Dansgaard-Oeschger interstadials (Greenland warm periods).

Seasonal cycle of circulation in the Antarctic Peninsula and the off-shelf transport of shelf waters into southern Drake Passage and Scotia Sea

NASA Astrophysics Data System (ADS)

Jiang, Mingshun; Charette, Matthew A.; Measures, Christopher I.; Zhu, Yiwu; Zhou, Meng

2013-06-01

The seasonal cycle of circulation and transport in the Antarctic Peninsula shelf region is investigated using a high-resolution (˜2 km) regional model based on the Regional Oceanic Modeling System (ROMS). The model also includes a naturally occurring tracer with a strong source over the shelf (radium isotope 228Ra, t1/2=5.8 years) to investigate the sediment Fe input and its transport. The model is spun-up for three years using climatological boundary and surface forcing and then run for the 2004-2006 period using realistic forcing. Model results suggest a persistent and coherent circulation system throughout the year consisting of several major components that converge water masses from various sources toward Elephant Island. These currents are largely in geostrophic balance, driven by surface winds, topographic steering, and large-scale forcing. Strong off-shelf transport of the Fe-rich shelf waters takes place over the northeastern shelf/slope of Elephant Island, driven by a combination of topographic steering, extension of shelf currents, and strong horizontal mixing between the ACC and shelf waters. These results are generally consistent with recent and historical observational studies. Both the shelf circulation and off-shelf transport show a significant seasonality, mainly due to the seasonal changes of surface winds and large-scale circulation. Modeled and observed distributions of 228Ra suggest that a majority of Fe-rich upper layer waters exported off-shelf around Elephant Island are carried by the shelfbreak current and the Bransfield Strait Current from the shallow sills between Gerlache Strait and Livingston Island, and northern shelf of the South Shetland Islands, where strong winter mixing supplies much of the sediment derived nutrients (including Fe) input to the surface layer.

Circulating microparticles from obstructive sleep apnea syndrome patients induce endothelin-mediated angiogenesis.

PubMed

Tual-Chalot, Simon; Gagnadoux, Frédéric; Trzepizur, Wojciech; Priou, Pascaline; Andriantsitohaina, Ramaroson; Martinez, M Carmen

2014-02-01

Microparticles are deemed true biomarkers and vectors of biological information between cells. Depending on their origin, the composition of microparticles varies and the subsequent message transported by them, such as proteins, mRNA, or miRNA, can differ. In obstructive sleep apnea syndrome (OSAS), circulating microparticles are associated with endothelial dysfunction by reducing endothelial-derived nitric oxide production. Here, we have analyzed the potential role of circulating microparticles from OSAS patients on the regulation of angiogenesis and the involved pathway. VEGF content carried by circulating microparticles from OSAS patients was increased when compared with microparticles from non-OSAS patients. Circulating microparticles from OSAS patients induced an increase of angiogenesis that was abolished in the presence of the antagonist of endothelin-1 receptor type B. In addition, endothelin-1 secretion was increased in human endothelial cells treated by OSAS microparticles. We highlight that circulating microparticles from OSAS patients can modify the secretome of endothelial cells leading to angiogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

Nutraceutical augmentation of circulating endothelial progenitor cells and hematopoietic stem cells in human subjects.

PubMed

Mikirova, Nina A; Jackson, James A; Hunninghake, Ron; Kenyon, Julian; Chan, Kyle W H; Swindlehurst, Cathy A; Minev, Boris; Patel, Amit N; Murphy, Michael P; Smith, Leonard; Ramos, Famela; Ichim, Thomas E; Riordan, Neil H

2010-04-08

The medical significance of circulating endothelial or hematopoietic progenitors is becoming increasing recognized. While therapeutic augmentation of circulating progenitor cells using G-CSF has resulted in promising preclinical and early clinical data for several degenerative conditions, this approach is limited by cost and inability to perform chronic administration. Stem-Kine is a food supplement that was previously reported to augment circulating EPC in a pilot study. Here we report a trial in 18 healthy volunteers administered Stem-Kine twice daily for a 2 week period. Significant increases in circulating CD133 and CD34 cells were observed at days 1, 2, 7, and 14 subsequent to initiation of administration, which correlated with increased hematopoietic progenitors as detected by the HALO assay. Augmentation of EPC numbers in circulation was detected by KDR-1/CD34 staining and colony forming assays. These data suggest Stem-Kine supplementation may be useful as a stimulator of reparative processes associated with mobilization of hematopoietic and endothelial progenitors.

Incidence of cervical human papillomavirus infection in systemic lupus erythematosus women.

PubMed

Mendoza-Pinto, C; García-Carrasco, M; Vallejo-Ruiz, V; Méndez-Martínez, S; Taboada-Cole, A; Etchegaray-Morales, I; Muñóz-Guarneros, M; Reyes-Leyva, J; López-Colombo, A

2017-08-01

Objectives Our objective was to study the incidence, persistence and clearance of human papillomavirus infection in systemic lupus erythematosus women and assess risk factors for persistence of human papillomavirus infection. Methods We carried out a prospective, observational cohort study of 127 systemic lupus erythematosus women. Patients were evaluated at baseline and at three years. Traditional and systemic lupus erythematosus women-related disease risk factors were collected. Gynaecological evaluations and cervical cytology screening were made. Human papillomavirus detection and genotyping were made by polymerase chain reaction and linear array. Results The cumulative prevalence of human papillomavirus infection increased from 22.8% at baseline to 33.8% at three years; p = < 0.001: 20.1% of patients experienced 43 incident infections. The risk of any human papillomavirus infection was 10.1 per 1000 patient-months. At three years, 47 (88.6%) prevalent infections were cleared. Independent risk factors associated with incident human papillomavirus infection included more lifetime sexual partners (odds ratio = 1.8, 95% confidence interval = 1.11-3.0) and cumulative cyclophosphamide dose (odds ratio = 3.9, 95% confidence interval = 1.2-12.8). Conclusions In systemic lupus erythematosus women, the cumulative prevalence of human papillomavirus infection, including high risk-human papillomavirus and multiple human papillomavirus infections, may increase over time. Most persistent infections were low risk-human papillomavirus. The number of lifetime sexual partners and the cumulative cyclophosphamide dose were independently associated with incident human papillomavirus infection.

A Review of the Antiviral Susceptibility of Human and Avian Influenza Viruses over the Last Decade

PubMed Central

Oh, Ding Yuan; Hurt, Aeron C.

2014-01-01

Antivirals play an important role in the prevention and treatment of influenza infections, particularly in high-risk or severely ill patients. Two classes of influenza antivirals have been available in many countries over the last decade (2004–2013), the adamantanes and the neuraminidase inhibitors (NAIs). During this period, widespread adamantane resistance has developed in circulating influenza viruses rendering these drugs useless, resulting in the reliance on the most widely available NAI, oseltamivir. However, the emergence of oseltamivir-resistant seasonal A(H1N1) viruses in 2008 demonstrated that NAI-resistant viruses could also emerge and spread globally in a similar manner to that seen for adamantane-resistant viruses. Previously, it was believed that NAI-resistant viruses had compromised replication and/or transmission. Fortunately, in 2013, the majority of circulating human influenza viruses remain sensitive to all of the NAIs, but significant work by our laboratory and others is now underway to understand what enables NAI-resistant viruses to retain the capacity to replicate and transmit. In this review, we describe how the susceptibility of circulating human and avian influenza viruses has changed over the last ten years and describe some research studies that aim to understand how NAI-resistant human and avian influenza viruses may emerge in the future. PMID:24800107

Different aspects of virus persistence (review).

PubMed

Barnabishvili, N; Topuria, T; Gamtsemlidze, P; Topuria, M

2012-05-01

The article reviews different aspects of virus persistence in human organism. Persistence is a capability acquired and strengthened in the process of evolution of many viruses that is the means of maintenance of species. Viruses of measles, poliomyelitis, mite-like encephalitis, B and C hepatitis, herpes, retro and HIV viruses persist in human organism. Persistence is used by various viruses at various levels; they have different adaptive power and no different pathologic output. But in any case, the necessary condition is that virus should escape from elimination reactions of immune control system. At the same time, the important thing is not to save free virus but to save infected cell. While discussing long-term viral persistence, it is impossible to mark off distinctly the importance of biological participation of macroorganism and provoker in this process. The output of the relationship with infect cell is conditioned on the one hand by permissiveness of cell system, on the other hand by strain pathogen city. The details of attenuation mechanisms of microorganism's different reactions in cases of illness with the same strain are not known well yet. Although, it is clear that in chronic persistence the leading role still has immune system disbalance. In disbalance genesis of immunological equilibration virus-induced changes of immunocompetent cells are high.

Cutaneous human papillomaviruses persist on healthy skin.

PubMed

Hazard, Kristina; Karlsson, Anna; Andersson, Kristin; Ekberg, Henrik; Dillner, Joakim; Forslund, Ola

2007-01-01

Cutaneous human papillomaviruses (HPVs) are frequently found in healthy skin and have also been implicated in non-melanoma skin cancer. For genital HPV types, a persistent infection with one of the high-risk types is a prerequisite for the development of cervical cancer. However, there is only limited data on whether infections with cutaneous HPV types persist over time. Serial forehead swab samples collected from 63 volunteers (42 healthy individuals and 31 renal transplant recipients (RTRs)), sampled 6.3 years (range: 5.0-7.0 years) apart, were analyzed for HPV using general primer PCR, cloning, and sequencing. Among the healthy individuals, the prevalences of HPV were 69% (29/42) at enrolment and 71% (30/42) at follow-up. Among the individuals positive at baseline, 48% (14/29) had a persistent infection. Among the RTRs, 71% (15/21) were positive for HPV at enrolment and 90% (19/21) at follow-up. A persistent infection was detected in 33% (5/15). In total, HPV was detected in 44 of the samples collected at baseline and the same virus was found at follow-up in 43% (19/44). Persistence was not significantly associated with age, sex, immunosuppressive treatment, history of warts, or genus of HPV. We conclude that cutaneous HPV infections commonly persist over several years on healthy skin.

The genospecies B. burgdorferi s.l., isolated from ticks and from neurological patients with suspected Lyme borreliosis.

PubMed

Bazovska, Sylvia; Durovska, Judita; Derdakova, Marketa; Taragelova, Veronika; Pancak, Jaroslav; Zaborska, Magdalena; Traubner, Pavel

2011-01-01

Lyme borreliosis (LB) is the most disseminated tick-borne disease in the Northern hemisphere, and infestation with ticks is one of the essential factors influencing transmission of the disease to humans. This work intends to compare the occurrence of borrelia circulating in indigenous ticks and in patients suffering from neurological diseases. The total of 660 nymphs and 567 adult ticks from the Bratislava and Košice areas was examined over the years 2001-2004, and the cerebrospinal fluid (CSF) of 82 neurological patients suffering from suspected Lyme borreliosis infection was investigated in the 2007-2009 period, using the polymerase chain reaction method (PCR). PCR investigation proved presence of borrelia in 23.3% of the total 1227 ticks; of these, co-infection was found in 2.7% of all ticks. Borrelia garinii (9.9%) and B. valaisaina (9.2%) were the prevalent types. PCR investigation of the CSF samples of 32 patients with clinically diagnosed Lyme borreliosis showed the presence of B. burgdorferi s.l. in 17 cases. Positive results were found also in patients with unclear or different diagnoses. In cases where the genospecies could be identified, B. garinii was most frequently found (8x), followed with B. burgdorferi s.s. (4×) and B. afzelii (3×). The high infestation level of ticks with borrelia, mainly with B. garinii which is the most-often documented borrelia species identified in neurological patients, is indicative of a high risk of this contamination in Slovakia. B. garinii were found also in our neuroborreliosis patients, whereas their proof in the CSF of patients with suspected neuroborreliosis or with a different clinical diagnosis pointed upon their persistence after an infectious experience. However, knowledge of not only the genospecies but also of the genotypes capable of eliciting an invasive disorder would be necessary for better clarification of the relationship between borrelia and their peccant capacity. Identification of the invasive borrelia types circulating in nature, and clarification of the vector vs. human infection incidence relationship is of importance from the aspect of detailed knowledge of the epidemiology of this disease.

Nutrient pumping by submesoscale circulations in the mauritanian upwelling system

NASA Astrophysics Data System (ADS)

Hosegood, P. J.; Nightingale, P. D.; Rees, A. P.; Widdicombe, C. E.; Woodward, E. M. S.; Clark, D. R.; Torres, R. J.

2017-12-01

Observations made within a cold filament in the Mauritanian upwelling system demonstrate that intense submesoscale circulations at the peripheral edges of the filament are likely responsible for anomalously high levels of observed primary productivity by resupplying nutrients to the euphotic zone. Measurements made on the shelf within the recently upwelled water reveal that primary production (PP) of 8.2 gC/m-2 day-1 was supported by nitrate concentrations (NC) of 8 mmol m-3. Towards the front that defined the edge of the filament containing the upwelled water as it was transported offshore, PP dropped to 1.6 gC m-2 day-1 whilst NC dropped to 5.5 mmol m-3. Thus, whilst the observed nutrients on the shelf accounted for 90% of new production, this value dropped to ∼60% near the filament's front after accounting for vertical turbulent fluxes and Ekman pumping. We demonstrate that the N15 was likely to have been supplied at the front by submesoscale circulations that were directly measured as intense vertical velocities ⩾100 m day-1 by a drifting acoustic Doppler current profiler that crossed a submesoscale surface temperature front. At the same time, a recently released tracer was subducted out of the mixed layer within 24 h of release, providing direct evidence that the frontal circulations were capable of accessing the reservoir of nutrients beneath the pycnocline. The susceptibility of the filament edge to submesoscale instabilities was demonstrated by O(1) Rossby numbers at horizontal scales of 1-10 km. The frontal circulations are consistent with instabilities arising from a wind-driven nonlinear Ekman buoyancy flux generated by the persistent northerly wind stress that has a down-front component at the northern edge of the inshore section of the filament. The prevalence of submesoscale instabilities and their associated vertical circulations are proposed to be a key mechanism operating at sub-grid scales and sustaining new production throughout the upwelling system.

Circulating vitamin D concentration and age-related macular degeneration: Systematic review and meta-analysis.

PubMed

Annweiler, Cedric; Drouet, Morgane; Duval, Guillaume T; Paré, Pierre-Yves; Leruez, Stephanie; Dinomais, Mickael; Milea, Dan

2016-06-01

Vitamin D may be involved in ocular function in older adults, but there is no current consensus on a possible association between circulating concentrations of 25-hydroxyvitamin D (25OHD) and the occurrence of age-related macular degeneration (AMD). Our objective was to systematically review and quantitatively assess the association of circulating 25OHD concentration with AMD. A Medline search was conducted in November 2015, with no date limit, using the MeSH terms "Vitamin D" OR "Vitamin D deficiency" OR "Ergocalciferols" OR 'Cholecalciferol' combined with "Age-related macular degeneration" OR "Macular degeneration" OR "Retinal degeneration" OR "Macula lutea" OR "Retina". Fixed and random-effects meta-analyses were performed to compute (i) standard mean difference in 25OHD concentration between AMD and non-AMD patients; (ii) AMD risk according to circulating 25OHD concentration. Of the 243 retrieved studies, 11 observational studies-10 cross-sectional studies and 1 cohort study-met the selection criteria. The number of participants ranged from 65 to 17,045 (52-100% women), and the number with AMD ranged from 31 to 1440. Circulating 25OHD concentration was 15% lower in AMD compared with non-AMD on average. AMD was inversely associated with the highest 25OHD quintile compared with the lowest (summary odds ratio (OR)=0.83 [95%CI:0.71-0.97]), notably late AMD (summary OR=0.47 [95%CI:0.28-0.79]). Circulating 25OHD<50nmol/L was also associated with late-stage AMD (summary OR=2.18 [95%CI:1.34-3.56]), an association that did not persist when all categories of AMD were considered (summary OR=1.26 [95%CI:0.90-1.76]). In conclusion, this meta-analysis provides evidence that high 25OHD concentrations may be protective against AMD, and that 25OHD concentrations below 50nmol/L are associated with late AMD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The role of precipitation in aerosol-induced changes in northern hemisphere wintertime stationary waves

NASA Astrophysics Data System (ADS)

Lewinschal, A.; Ekman, A. M. L.; Körnich, H.

2012-04-01

Aerosol particles have a considerable impact on the energy budget of the atmosphere due to their ability to scatter and absorb incoming solar radiation. Persistent particle emissions in certain regions of the world have lead to quasi-permanent aerosol forcing patterns. This spatially varying forcing pattern has the potential to modify temperature gradients that in turn alter pressure gradients and the atmospheric circulation. This study focuses on the effect of aerosol direct radiative forcing on northern hemisphere wintertime stationary waves. A global general circulation model based on the ECMWF operational forecast model is applied (EC-Earth). Aerosols are prescribed as monthly mean mixing ratios of sulphate, black carbon, organic carbon, dust and sea salt. Only the direct aerosol effect is considered. The climatic change is defined as the difference between model simulations using present-day and pre-industrial concentrations of aerosol particles. Data from 40-year long simulations using a coupled ocean-atmosphere model system are used. In EC-Earth, the high aerosol loading over South Asia leads to a surface cooling, which appears to enhance the South Asian winter monsoon and weaken the Indian Ocean Walker circulation. The anomalous Walker circulation leads to changes in tropical convective precipitation and consequent changes in latent heat release which effectively acts to generate planetary scale waves propagating into the extra-tropics. Using a steady-state linear model we verify that the aerosol-induced anomalous convective precipitation is a crucial link between the wave changes and the direct aerosol radiative forcing.

Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats

PubMed Central

2014-01-01

Welding fume is an exposure that consists of a mixture of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection in animal models, the question arose whether the dysfunction persisted systemically. Our aim was to evaluate the circulating leukocyte population in terms of cellular activation, presence of oxidative stress, and functionality after a secondary challenge, following welding fume exposure. Rats were intratracheally instilled (ITI) with PBS or 2 mg of welding fume collected from a stainless steel weld. Rats were sacrificed 4 and 24 h post-exposure and whole blood was collected. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation with LPS utilizing TruCulture technology. In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy. Welding fume exposure had rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of welding fume reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress. These findings support previous studies of an inadequate pulmonary immune response following a metal-rich exposure and extend those findings showing leukocyte dysfunction occurs systemically. PMID:25123171