EtpE Binding to DNase X Induces Ehrlichial Entry via CD147 and hnRNP-K Recruitment, Followed by Mobilization of N-WASP and Actin.

PubMed

Mohan Kumar, Dipu; Lin, Mingqun; Xiong, Qingming; Webber, Mathew James; Kural, Comert; Rikihisa, Yasuko

2015-11-03

Obligate intracellular bacteria, such as Ehrlichia chaffeensis, perish unless they can enter eukaryotic cells. E. chaffeensis is the etiological agent of human monocytic ehrlichiosis, an emerging infectious disease. To infect cells, Ehrlichia uses the C terminus of the outer membrane invasin entry-triggering protein (EtpE) of Ehrlichia (EtpE-C), which directly binds the mammalian cell surface glycosylphosphatidyl inositol-anchored protein, DNase X. How this binding drives Ehrlichia entry is unknown. Here, using affinity pulldown of host cell lysates with recombinant EtpE-C (rEtpE-C), we identified two new human proteins that interact with EtpE-C: CD147 and heterogeneous nuclear ribonucleoprotein K (hnRNP-K). The interaction of CD147 with rEtpE-C was validated by far-Western blotting and coimmunoprecipitation of native EtpE with endogenous CD147. CD147 was ubiquitous on the cell surface and also present around foci of rEtpE-C-coated-bead entry. Functional neutralization of surface-exposed CD147 with a specific antibody inhibited Ehrlichia internalization and infection but not binding. Downregulation of CD147 by short hairpin RNA (shRNA) impaired E. chaffeensis infection. Functional ablation of cytoplasmic hnRNP-K by a nanoscale intracellular antibody markedly attenuated bacterial entry and infection but not binding. EtpE-C also interacted with neuronal Wiskott-Aldrich syndrome protein (N-WASP), which is activated by hnRNP-K. Wiskostatin, which inhibits N-WASP activation, and cytochalasin D, which inhibits actin polymerization, inhibited Ehrlichia entry. Upon incubation with host cell lysate, EtpE-C but not an EtpE N-terminal fragment stimulated in vitro actin polymerization in an N-WASP- and DNase X-dependent manner. Time-lapse video images revealed N-WASP recruitment at EtpE-C-coated bead entry foci. Thus, EtpE-C binding to DNase X drives Ehrlichia entry by engaging CD147 and hnRNP-K and activating N-WASP-dependent actin polymerization. Ehrlichia chaffeensis, an obligate intracellular bacterium, causes a blood-borne disease called human monocytic ehrlichiosis, one of the most prevalent life-threatening emerging tick-transmitted infectious diseases in the United States. The survival of Ehrlichia bacteria, and hence, their ability to cause disease, depends on their specific mode of entry into eukaryotic host cells. Understanding the mechanism by which E. chaffeensis enters cells will create new opportunities for developing effective therapies to prevent bacterial entry and disease in humans. Our findings reveal a novel cellular signaling pathway triggered by an ehrlichial surface protein called EtpE to induce its infectious entry. The results are also important from the viewpoint of human cell physiology because three EtpE-interacting human proteins, DNase X, CD147, and hnRNP-K, are hitherto unknown partners that drive the uptake of small particles, including bacteria, into human cells. Copyright © 2015 Mohan Kumar et al.

Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor Antagonists

PubMed Central

Cheng, Han; Lear-Rooney, Calli M.; Johansen, Lisa; Varhegyi, Elizabeth; Chen, Zheng W.; Olinger, Gene G.

2015-01-01

ABSTRACT Filoviruses, consisting of Ebola virus (EBOV) and Marburg virus (MARV), are among the most lethal infectious threats to mankind. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with high mortality rates. Since there is currently no vaccine or antiviral therapy approved for humans, there is an urgent need to develop prophylactic and therapeutic options for use during filoviral outbreaks and bioterrorist attacks. One of the ideal targets against filoviral infection and diseases is at the entry step, which is mediated by the filoviral glycoprotein (GP). In this report, we screened a chemical library of small molecules and identified numerous inhibitors, which are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs, including histamine receptors, 5-HT (serotonin) receptors, muscarinic acetylcholine receptor, and adrenergic receptor. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. The time-of-addition experiment and microscopic studies suggest that GPCR antagonists block filoviral entry at a step following the initial attachment but prior to viral/cell membrane fusion. These results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy. IMPORTANCE Infection of Ebola virus and Marburg virus can cause severe illness in humans with a high mortality rate, and currently there is no FDA-approved vaccine or therapeutic treatment available. The 2013-2015 epidemic in West Africa underscores a lack of our understanding in the infection and pathogenesis of these viruses and the urgency of drug discovery and development. In this study, we have identified numerous inhibitors that are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. Our results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy. PMID:26202243

Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor Antagonists.

PubMed

Cheng, Han; Lear-Rooney, Calli M; Johansen, Lisa; Varhegyi, Elizabeth; Chen, Zheng W; Olinger, Gene G; Rong, Lijun

2015-10-01

Filoviruses, consisting of Ebola virus (EBOV) and Marburg virus (MARV), are among the most lethal infectious threats to mankind. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with high mortality rates. Since there is currently no vaccine or antiviral therapy approved for humans, there is an urgent need to develop prophylactic and therapeutic options for use during filoviral outbreaks and bioterrorist attacks. One of the ideal targets against filoviral infection and diseases is at the entry step, which is mediated by the filoviral glycoprotein (GP). In this report, we screened a chemical library of small molecules and identified numerous inhibitors, which are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs, including histamine receptors, 5-HT (serotonin) receptors, muscarinic acetylcholine receptor, and adrenergic receptor. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. The time-of-addition experiment and microscopic studies suggest that GPCR antagonists block filoviral entry at a step following the initial attachment but prior to viral/cell membrane fusion. These results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy. Infection of Ebola virus and Marburg virus can cause severe illness in humans with a high mortality rate, and currently there is no FDA-approved vaccine or therapeutic treatment available. The 2013-2015 epidemic in West Africa underscores a lack of our understanding in the infection and pathogenesis of these viruses and the urgency of drug discovery and development. In this study, we have identified numerous inhibitors that are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. Our results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

HPV-16 virions can remain infectious for 2 weeks on senescent cells but require cell cycle re-activation to allow virus entry.

PubMed

Broniarczyk, Justyna; Ring, Nadja; Massimi, Paola; Giacca, Mauro; Banks, Lawrence

2018-01-16

Successful infection with Human Papillomaviruses requires mitosis, when incoming viral genomes gain access to nuclear components. However, very little is known about how long HPV particles can remain infectious in non-dividing cells or in which cellular compartments these viruses may reside. To investigate these questions we have used BJ cells as a reversible model of senescence and show that HPV-16 can only infect early-passage proliferating cells. Late-passage senescent cells are resistant to HPV infection, but this can be reversed by inducing cell cycle re-entry with a p53 siRNA. In senescent cells we find that efficient virus entry can be attained upon cell cycle re-entry 16 days after infection, demonstrating that HPV can persist for 2 weeks prior to induction of mitosis. However, exposing cells to anti-HPV-16 L1 neutralising antibody blocks infection at these late time points, suggesting that the virions reside near the cell surface. Indeed, immunofluorescence analysis shows that virions accumulate on the cell surface of senescent cells and only enter endocytic vesicles upon stimulation with p53 siRNA. These results demonstrate that HPV-16 virions can remain viable on a non-dividing cell for extended periods of time, but are nonetheless vulnerable to antibody-induced neutralisation throughout.

Role of endocytosis and cathepsin-mediated activation in Nipah virus entry

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

Diederich, Sandra; Thiel, Lena; Maisner, Andrea

The recent discovery that the Nipah virus (NiV) fusion protein (F) is activated by endosomal cathepsin L raised the question if NiV utilize pH- and protease-dependent mechanisms of entry. We show here that the NiV receptor ephrin B2, virus-like particles and infectious NiV are internalized from the cell surface. However, endocytosis, acidic pH and cathepsin-mediated cleavage are not necessary for the initiation of infection of new host cells. Our data clearly demonstrate that proteolytic activation of the NiV F protein is required before incorporation into budding virions but not after virus entry.

Novel functional hepatitis C virus glycoprotein isolates identified using an optimized viral pseudotype entry assay.

PubMed

Urbanowicz, Richard A; McClure, C Patrick; King, Barnabas; Mason, Christopher P; Ball, Jonathan K; Tarr, Alexander W

2016-09-01

Retrovirus pseudotypes are a highly tractable model used to study the entry pathways of enveloped viruses. This model has been extensively applied to the study of the hepatitis C virus (HCV) entry pathway, preclinical screening of antiviral antibodies and for assessing the phenotype of patient-derived viruses using HCV pseudoparticles (HCVpp) possessing the HCV E1 and E2 glycoproteins. However, not all patient-isolated clones produce particles that are infectious in this model. This study investigated factors that might limit phenotyping of patient-isolated HCV glycoproteins. Genetically related HCV glycoproteins from quasispecies in individual patients were discovered to behave very differently in this entry model. Empirical optimization of the ratio of packaging construct and glycoprotein-encoding plasmid was required for successful HCVpp genesis for different clones. The selection of retroviral packaging construct also influenced the function of HCV pseudoparticles. Some glycoprotein constructs tolerated a wide range of assay parameters, while others were much more sensitive to alterations. Furthermore, glycoproteins previously characterized as unable to mediate entry were found to be functional. These findings were validated using chimeric cell-cultured HCV bearing these glycoproteins. Using the same empirical approach we demonstrated that generation of infectious ebolavirus pseudoviruses (EBOVpv) was also sensitive to the amount and ratio of plasmids used, and that protocols for optimal production of these pseudoviruses are dependent on the exact virus glycoprotein construct. These findings demonstrate that it is crucial for studies utilizing pseudoviruses to conduct empirical optimization of pseudotype production for each specific glycoprotein sequence to achieve optimal titres and facilitate accurate phenotyping.

Bacteriophage-associated gene transfer in pneumococcus: transduction or pseudotransduction?

PubMed Central

Porter, R D; Shoemaker, N B; Rampe, G; Guild, W R

1979-01-01

Lysates of pneumococcal phage PG24 transferred genes from one host to another in a process with many of the properties of generalized transduction, in that the host genes were packaged in DNase-resistant particles that closely resembled infectious phage in physical properties, adsorbed to the recipient cells like phage, and were inhibited by antisera to the phage and by trypsin. However, phage processes did not complete the transfer of host DNA as they did phage DNA. Instead, gene transfer required development of competence and entry of the host DNA by the endonuclease-dependent pathway used for transforming and transfecting DNA. This process often occurred on the assay plate hours after adsorption of the particles to the cells, and the transfer was DNase sensitive if challenged at this time. Phenotypic expression was therefore also delayed. The product of entry was like that in transformation, a single strand of DNA that integrates by formation of a hex-sensitive donor-recipient heteroduplex. Whether this gene transfer process is unique to this system or is only the first one described is not clear. The term "pseudotransduction" may be useful in calling attention to its unexpected features. The DNA of PG24 phage has anomalous physical properties reflecting unusual bases. Images PMID:33154

A Dual Role for the Nonreceptor Tyrosine Kinase Pyk2 during the Intracellular Trafficking of Human Papillomavirus 16.

PubMed

Gottschalk, Elinor Y; Meneses, Patricio I

2015-09-01

The infectious process of human papillomaviruses (HPVs) has been studied considerably, and many cellular components required for viral entry and trafficking continue to be revealed. In this study, we investigated the role of the nonreceptor tyrosine kinase Pyk2 during HPV16 pseudovirion infection of human keratinocytes. We found that Pyk2 is necessary for infection and appears to be involved in the intracellular trafficking of the virus. Small interfering RNA-mediated reduction of Pyk2 resulted in a significant decrease in infection but did not prevent viral entry at the plasma membrane. Pyk2 depletion resulted in altered endolysosomal trafficking of HPV16 and accelerated unfolding of the viral capsid. Furthermore, we observed retention of the HPV16 pseudogenome in the trans-Golgi network (TGN) in Pyk2-depleted cells, suggesting that the kinase could be required for the viral DNA to exit the TGN. While Pyk2 has previously been shown to function during the entry of enveloped viruses at the plasma membrane, the kinase has not yet been implicated in the intracellular trafficking of a nonenveloped virus such as HPV. Additionally, these data enrich the current literature on Pyk2's function in human keratinocytes. In this study, we investigated the role of the nonreceptor tyrosine kinase Pyk2 during human papillomavirus (HPV) infection of human skin cells. Infections with high-risk types of HPV such as HPV16 are the leading cause of cervical cancer and a major cause of genital and oropharyngeal cancer. As a nonenveloped virus, HPV enters cells by interacting with cellular receptors and established cellular trafficking routes to ensure that the viral DNA reaches the nucleus for productive infection. This study identified Pyk2 as a cellular component required for the intracellular trafficking of HPV16 during infection. Understanding the infectious pathways of HPVs is critical for developing additional preventive therapies. Furthermore, this study advances our knowledge of intracellular trafficking processes in keratinocytes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Statins Suppress Ebola Virus Infectivity by Interfering with Glycoprotein Processing.

PubMed

Shrivastava-Ranjan, Punya; Flint, Mike; Bergeron, Éric; McElroy, Anita K; Chatterjee, Payel; Albariño, César G; Nichol, Stuart T; Spiropoulou, Christina F

2018-05-01

Ebola virus (EBOV) infection is a major public health concern due to high fatality rates and limited effective treatments. Statins, widely used cholesterol-lowering drugs, have pleiotropic mechanisms of action and were suggested as potential adjunct therapy for Ebola virus disease (EVD) during the 2013-2016 outbreak in West Africa. Here, we evaluated the antiviral effects of statin (lovastatin) on EBOV infection in vitro Statin treatment decreased infectious EBOV production in primary human monocyte-derived macrophages and in the hepatic cell line Huh7. Statin treatment did not interfere with viral entry, but the viral particles released from treated cells showed reduced infectivity due to inhibition of viral glycoprotein processing, as evidenced by decreased ratios of the mature glycoprotein form to precursor form. Statin-induced inhibition of infectious virus production and glycoprotein processing was reversed by exogenous mevalonate, the rate-limiting product of the cholesterol biosynthesis pathway, but not by low-density lipoprotein. Finally, statin-treated cells produced EBOV particles devoid of the surface glycoproteins required for virus infectivity. Our findings demonstrate that statin treatment inhibits EBOV infection and suggest that the efficacy of statin treatment should be evaluated in appropriate animal models of EVD. IMPORTANCE Treatments targeting Ebola virus disease (EVD) are experimental, expensive, and scarce. Statins are inexpensive generic drugs that have been used for many years for the treatment of hypercholesterolemia and have a favorable safety profile. Here, we show the antiviral effects of statins on infectious Ebola virus (EBOV) production. Our study reveals a novel molecular mechanism in which statin regulates EBOV particle infectivity by preventing glycoprotein processing and incorporation into virus particles. Additionally, statins have anti-inflammatory and immunomodulatory effects. Since inflammation and dysregulation of the immune system are characteristic features of EVD, statins could be explored as part of EVD therapeutics.

Screening for infectious diseases at international airports: the Frankfurt model.

PubMed

Gaber, Walter; Goetsch, Udo; Diel, Roland; Doerr, Hans W; Gottschalk, René

2009-07-01

Historically, ships brought infectious diseases to the continents of the world, but in this modern era, infectious diseases and pandemics are primarily spread through aviation as a mode of travel. This is a significant issue in the realm of infection control because of the increased potential for the rapid worldwide transmission and spread of disease. Although the transmission of infectious diseases to airline passengers inside an aircraft is a rare occurrence, it is essential to implement entry and exit screening procedures at airports within the context of the International Health Regulations (IHR) in order to slow down the spread of infection, especially during the early phases of a pandemic event. Currently, there are no standardized procedures for health screening at airports, thus allowing individual regional authorities to determine what they deem to be appropriate screening measures for implementation. In this paper, we will discuss a new pragmatic approach for entry and exit screening procedures at international airports, propose a new classification system for contacts within the aircraft, and discuss changing the fixed enforcement of standardized community mitigation measures to the implementation of measures that correspond to specific characteristics of individual pathogenic agents. The proposed catalog of screening measures is aimed at attaining the goals of the IHR, which states that the measures should be reasonable while avoiding inconvenience or harm to passengers and should not be any more disruptive to the smooth handling of passenger traffic than is necessary.

Infectious rotavirus enters cells by direct cell membrane penetration, not by endocytosis

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

Kaljot, K.T.; Shaw, R.D.; Greenberg, H.B.

1988-04-01

Rotaviruses are icosahedral viruses with a segmented, double-stranded RNA genome. They are the major cause of severe infantile infectious diarrhea. Rotavirus growth in tissue culture is markedly enhanced by pretreatment of virus with trypsin. Trypsin activation is associated with cleavage of the viral hemagglutinin (viral protein 3 (VP3); 88 kilodaltons) into two fragments (60 and 28 kilodaltons). The mechanism by which proteolytic cleavage leads to enhanced growth is unknown. To determine whether trypsin treatment affected rotavirus internalization, the authors studied the kinetics of entry of infectious rhesus rotavirus (RRV) into MA104 cells. Trypsin-activated RRV was internalized with a half-time ofmore » 3 to 5 min, while nonactivated virus disappeared from the cell surface with a half-time of 30 to 50 min. In contrast to trypsin-activated RRV, loss of nonactivated RRV from the cell surface did not result in the appearance of infection, as measured by plaque formation. Purified trypsin-activated RRV added to cell monolayers at pH 7.4 mediated {sup 51}Cr, ({sup 14}C)choline, and ({sup 3}H)inositol released from prelabeled MA104 cells. This release could be specifically blocked by neutralizing antibodies to VP3. These results suggest that MA104 cell infection follows the rapid entry of trypsin-activated RRV by direct cell membrane penetration. Cell membrane penetration of infectious RRV is initiated by trypsin cleavage of VP3. Neutralizing antibodies can inhibit this direct membrane penetration.« less

Influence of Humans on Evolution and Mobilization of Environmental Antibiotic Resistome

PubMed Central

Gaze, William H.; Krone, Stephen M.; Larsson, D.G. Joakim; Li, Xian-Zhi; Robinson, Joseph A.; Simonet, Pascal; Smalla, Kornelia; Timinouni, Mohammed; Topp, Ed; Wellington, Elizabeth M.; Zhu, Yong-Guan

2013-01-01

The clinical failure of antimicrobial drugs that were previously effective in controlling infectious disease is a tragedy of increasing magnitude that gravely affects human health. This resistance by pathogens is often the endpoint of an evolutionary process that began billions of years ago in non–disease-causing microorganisms. This environmental resistome, its mobilization, and the conditions that facilitate its entry into human pathogens are at the heart of the current public health crisis in antibiotic resistance. Understanding the origins, evolution, and mechanisms of transfer of resistance elements is vital to our ability to adequately address this public health issue. PMID:23764294

Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load

USGS Publications Warehouse

Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael

2012-01-01

Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed.

Potent Inhibition of Feline Coronaviruses with Peptidyl Compounds Targeting Coronavirus 3C-like Protease

PubMed Central

Kim, Yunjeong; Mandadapu, Sivakoteswara Rao; Groutas, William C.; Chang, Kyeong-Ok

2012-01-01

Feline coronavirus infection is common among domestic and exotic felid species and usually associated with mild or asymptomatic enteritis; however, feline infectious peritonitis (FIP) is a fatal disease of cats that is caused by systemic infection with a feline infectious peritonitis virus (FIPV), a variant of feline enteric coronavirus (FECV). Currently, there is no specific treatment approved for FIP despite the importance of FIP as the leading infectious cause of death in young cats. During the replication process, coronavirus produces viral polyproteins that are processed into mature proteins by viral proteases, the main protease (3C-like [3CL] protease) and the papain-like protease. Since the cleavages of viral polyproteins are an essential step for virus replication, blockage of viral protease is an attractive target for therapeutic intervention. Previously, we reported the generation of broad-spectrum peptidyl inhibitors against viruses that possess a 3C or 3CL protease. In this study, we further evaluated the antiviral effects of the peptidyl inhibitors against feline coronaviruses, and investigated the interaction between our protease inhibitor and a cathepsin B inhibitor, an entry blocker, against feline coronaviruses in cell culture. Herein we report that our compounds behave as reversible, competitive inhibitors of 3CL protease, potently inhibited the replication of feline coronaviruses (EC50 in a nanomolar range) and, furthermore, the combination of cathepsin B and 3CL protease inhibitors led to a strong synergistic interaction against feline coronaviruses in cell culture systems. PMID:23219425

Determining the Involvement and Therapeutic Implications of Host Cellular Factors in Hepatitis C Virus Cell-to-Cell Spread

PubMed Central

Barretto, Naina; Sainz, Bruno; Hussain, Snawar

2014-01-01

ABSTRACT Hepatitis C virus (HCV) infects 180 million people worldwide and is a leading cause of liver diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma. It has been shown that HCV can spread to naive cells using two distinct entry mechanisms, “cell-free” entry of infectious extracellular virions that have been released by infected cells and direct “cell-to-cell” transmission. Here, we examined host cell requirements for HCV spread and found that the cholesterol uptake receptor NPC1L1, which we recently identified as being an antiviral target involved in HCV cell-free entry/spread, is also required for the cell-to-cell spread. In contrast, the very low density lipoprotein (VLDL) pathway, which is required for the secretion of cell-free infectious virus and thus has been identified as an antiviral target for blocking cell-free virus secretion/spread, is not required for cell-to-cell spread. Noting that HCV cell-free and cell-to-cell spread share some common factors but not others, we tested the therapeutic implications of these observations and demonstrate that inhibitors that target cell factors required for both forms of HCV spread exhibit synergy when used in combination with interferon (a representative inhibitor of intracellular HCV production), while inhibitors that block only cell-free spread do not. This provides insight into the mechanistic basis of synergy between interferon and HCV entry inhibitors and highlights the broader, previously unappreciated impact blocking HCV cell-to-cell spread can have on the efficacy of HCV combination therapies. IMPORTANCE HCV can spread to naive cells using distinct mechanisms: “cell-free” entry of extracellular virus and direct “cell-to-cell” transmission. Herein, we identify the host cell HCV entry factor NPC1L1 as also being required for HCV cell-to-cell spread, while showing that the VLDL pathway, which is required for the secretion of cell-free infectious virus, is not required for cell-to-cell spread. While both these host factors are considered viable antiviral targets, we demonstrate that only inhibitors that block factors required for both forms of HCV entry/spread (i.e., NPC1L1) exhibit synergy when used in combination with interferon, while inhibitors that block factors required only for cell-free spread (i.e., VLDL pathway components) do not. Thus, this study advances our understanding of HCV cell-to-cell spread, provides mechanistic insight into the basis of drug synergy, and highlights inhibition of HCV spread as a previously unappreciated consideration in HCV therapy design. PMID:24554660

76 FR 66731 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-27

...; Role of Chemokine Receptors in HIV- 1 Entry and Cancer. Date: November 22, 2011 Time: 12 p.m. to 1 p.m... concerning individuals associated with the grant applications, the disclosure of which would constitute a...

The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry.

PubMed

Meertens, Laurent; Carnec, Xavier; Lecoin, Manuel Perera; Ramdasi, Rasika; Guivel-Benhassine, Florence; Lew, Erin; Lemke, Greg; Schwartz, Olivier; Amara, Ali

2012-10-18

Dengue viruses (DVs) are responsible for the most medically relevant arboviral diseases. However, the molecular interactions mediating DV entry are poorly understood. We determined that TIM and TAM proteins, two receptor families that mediate the phosphatidylserine (PtdSer)-dependent phagocytic removal of apoptotic cells, serve as DV entry factors. Cells poorly susceptible to DV are robustly infected after ectopic expression of TIM or TAM receptors. Conversely, DV infection of susceptible cells is inhibited by anti-TIM or anti-TAM antibodies or knockdown of TIM and TAM expression. TIM receptors facilitate DV entry by directly interacting with virion-associated PtdSer. TAM-mediated infection relies on indirect DV recognition, in which the TAM ligand Gas6 acts as a bridging molecule by binding to PtdSer within the virion. This dual mode of virus recognition by TIM and TAM receptors reveals how DVs usurp the apoptotic cell clearance pathway for infectious entry. Copyright © 2012 Elsevier Inc. All rights reserved.

Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses.

PubMed

Fernandez-Garcia, Maria Dolores; Meertens, Laurent; Chazal, Maxime; Hafirassou, Mohamed Lamine; Dejarnac, Ophélie; Zamborlini, Alessia; Despres, Philippe; Sauvonnet, Nathalie; Arenzana-Seisdedos, Fernando; Jouvenet, Nolwenn; Amara, Ali

2016-02-09

The live attenuated yellow fever virus (YFV) vaccine 17D stands as a "gold standard" for a successful vaccine. 17D was developed empirically by passaging the wild-type Asibi strain in mouse and chicken embryo tissues. Despite its immense success, the molecular determinants for virulence attenuation and immunogenicity of the 17D vaccine are poorly understood. 17D evolved several mutations in its genome, most of which lie within the envelope (E) protein. Given the major role played by the YFV E protein during virus entry, it has been hypothesized that the residues that diverge between the Asibi and 17D E proteins may be key determinants of attenuation. In this study, we define the process of YFV entry into target cells and investigate its implication in the activation of the antiviral cytokine response. We found that Asibi infects host cells exclusively via the classical clathrin-mediated endocytosis, while 17D exploits a clathrin-independent pathway for infectious entry. We demonstrate that the mutations in the 17D E protein acquired during the attenuation process are sufficient to explain the differential entry of Asibi versus 17D. Interestingly, we show that 17D binds to and infects host cells more efficiently than Asibi, which culminates in increased delivery of viral RNA into the cytosol and robust activation of the cytokine-mediated antiviral response. Overall, our study reveals that 17D vaccine and Asibi enter target cells through distinct mechanisms and highlights a link between 17D attenuation, virus entry, and immune activation. The yellow fever virus (YFV) vaccine 17D is one of the safest and most effective live virus vaccines ever developed. The molecular determinants for virulence attenuation and immunogenicity of 17D are poorly understood. 17D was generated by serially passaging the virulent Asibi strain in vertebrate tissues. Here we examined the entry mechanisms engaged by YFV Asibi and the 17D vaccine. We found the two viruses use different entry pathways. We show that the mutations differentiating the Asibi envelope (E) protein from the 17D E protein, which arose during attenuation, are key determinants for the use of these distinct entry routes. Finally, we demonstrate that 17D binds and enters host cells more efficiently than Asibi. This results in a higher uptake of viral RNA into the cytoplasm and consequently a greater cytokine-mediated antiviral response. Overall, our data provide new insights into the biology of YFV infection and the mechanisms of viral attenuation. Copyright © 2016 Fernandez-Garcia et al.

Rotavirus RRV associates with lipid membrane microdomains during cell entry.

PubMed

Isa, Pavel; Realpe, Mauricio; Romero, Pedro; López, Susana; Arias, Carlos F

2004-05-01

Rotavirus cell entry is a multistep process, not completely understood, which requires at least four interactions between the virus and cell surface molecules. In this work, we investigated the role of the sphingolipid- and cholesterol-enriched lipid microdomains (rafts) in the entry of rotavirus strain RRV to MA104 cells. We found that ganglioside GM1, integrin subunits alpha2 and beta3, and the heat shock cognate protein 70 (hsc70), all of which have been implicated as rotavirus receptors, are associated with TX-100 and Lubrol WX detergent-resistant membranes (DRMs). Integrin subunits alpha2 and beta3 were found to be particularly enriched in DRMs resistant to lysis by Lubrol WX. When purified RRV particles were incubated with cells at 4 degrees C, about 10% of the total infectious virus was found associated with DRMs, and the DRM-associated virus increased to 37% in Lubrol-resistant membrane domains after 60-min incubation at 37 degrees C. The virus was excluded from DRMs if the cells were treated with methyl-beta-cyclodextrin (MbetaCD). Immunoblot analysis of the viral proteins showed that the virus surface proteins became enriched in DRMs upon incubation at 37 degrees C, being almost exclusively localized in Lubrol-resistant DRMs after 60 min. These data suggest that detergent-resistant membrane domains play an important role in the cell entry of rotaviruses, which could provide a platform to facilitate the efficient interaction of the rotavirus receptors with the virus particle.

Gene Therapy Approaches to Human Immunodeficiency Virus and Other Infectious Diseases.

PubMed

Rogers, Geoffrey L; Cannon, Paula M

2017-10-01

Advances in gene therapy technologies, particularly in gene editing, are suggesting new avenues for the treatment of human immunodeficiency virus and other infectious diseases. This article outlines recent developments in antiviral gene therapies, including those based on the disruption of entry receptors or that target viral genomes using targeted nucleases, such as the CRISPR/Cas9 system. In addition, new ways to express circulating antiviral factors, such as antibodies, and approaches to harness and engineer the immune system to provide an antiviral effect that is not naturally achieved are described. Copyright © 2017 Elsevier Inc. All rights reserved.

Structure and Uncoating of Immature Adenovirus

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

Perez-Berna, A.J.; Mangel, W.; Marabini, R.

2009-09-18

Maturation via proteolytic processing is a common trait in the viral world and is often accompanied by large conformational changes and rearrangements in the capsid. The adenovirus protease has been shown to play a dual role in the viral infectious cycle: (a) in maturation, as viral assembly starts with precursors to several of the structural proteins but ends with proteolytically processed versions in the mature virion, and (b) in entry, because protease-impaired viruses have difficulties in endosome escape and uncoating. Indeed, viruses that have not undergone proteolytic processing are not infectious. We studied the three-dimensional structure of immature adenovirus particlesmore » as represented by the adenovirus type 2 thermosensitive mutant ts1 grown under non-permissive conditions and compared it with the mature capsid. Our three-dimensional electron microscopy maps at subnanometer resolution indicate that adenovirus maturation does not involve large-scale conformational changes in the capsid. Difference maps reveal the locations of unprocessed peptides pIIIa and pVI and help define their role in capsid assembly and maturation. An intriguing difference appears in the core, indicating a more compact organization and increased stability of the immature cores. We have further investigated these properties by in vitro disassembly assays. Fluorescence and electron microscopy experiments reveal differences in the stability and uncoating of immature viruses, both at the capsid and core levels, as well as disassembly intermediates not previously imaged.« less

Capturing a flavivirus pre-fusion intermediate.

PubMed

Kaufmann, Bärbel; Chipman, Paul R; Holdaway, Heather A; Johnson, Syd; Fremont, Daved H; Kuhn, Richard J; Diamond, Michael S; Rossmann, Michael G

2009-11-01

During cell entry of flaviviruses, low endosomal pH triggers the rearrangement of the viral surface glycoproteins to a fusion-active state that allows the release of the infectious RNA into the cytoplasm. In this work, West Nile virus was complexed with Fab fragments of the neutralizing mAb E16 and was subsequently exposed to low pH, trapping the virions in a pre-fusion intermediate state. The structure of the complex was studied by cryo-electron microscopy and provides the first structural glimpse of a flavivirus fusion intermediate near physiological conditions. A radial expansion of the outer protein layer of the virion was observed compared to the structure at pH 8. The resulting approximately 60 A-wide shell of low density between lipid bilayer and outer protein layer is likely traversed by the stem region of the E glycoprotein. By using antibody fragments, we have captured a structural intermediate of a virus that likely occurs during cell entry. The trapping of structural transition states by antibody fragments will be applicable for other processes in the flavivirus life cycle and delineating other cellular events that involve conformational rearrangements.

Structural and mechanistic studies of measles virus illuminate paramyxovirus entry.

PubMed

Plemper, Richard K; Brindley, Melinda A; Iorio, Ronald M

2011-06-01

Measles virus (MeV), a member of the paramyxovirus family of enveloped RNA viruses and one of the most infectious viral pathogens identified, accounts for major pediatric morbidity and mortality worldwide although coordinated efforts to achieve global measles control are in place. Target cell entry is mediated by two viral envelope glycoproteins, the attachment (H) and fusion (F) proteins, which form a complex that achieves merger of the envelope with target cell membranes. Despite continually expanding knowledge of the entry strategies employed by enveloped viruses, our molecular insight into the organization of functional paramyxovirus fusion complexes and the mechanisms by which the receptor binding by the attachment protein triggers the required conformational rearrangements of the fusion protein remain incomplete. Recently reported crystal structures of the MeV attachment protein in complex with its cellular receptors CD46 or SLAM and newly developed functional assays have now illuminated some of the fundamental principles that govern cell entry by this archetype member of the paramyxovirus family. Here, we review these advances in our molecular understanding of MeV entry in the context of diverse entry strategies employed by other members of the paramyxovirus family.

Comparative Analysis of Host Cell Entry of Ebola Virus From Sierra Leone, 2014, and Zaire, 1976.

PubMed

Hofmann-Winkler, Heike; Gnirß, Kerstin; Wrensch, Florian; Pöhlmann, Stefan

2015-10-01

The ongoing Ebola virus (EBOV) disease (EVD) epidemic in Western Africa is the largest EVD outbreak recorded to date and requires the rapid development and deployment of antiviral measures. The viral glycoprotein (GP) facilitates host cell entry and, jointly with cellular interaction partners, constitutes a potential target for antiviral intervention. However, it is unknown whether the GPs of the currently and previously circulating EBOVs use the same mechanisms for cellular entry and are thus susceptible to inhibition by the same antivirals and cellular defenses. Here, we show that the GPs of the EBOVs circulating in 1976 and 2014 transduce the same spectrum of target cells, use the same cellular factors for host cell entry, and are comparably susceptible to blockade by antiviral interferon-induced transmembrane proteins and neutralizing antibody KZ52. Thus, the viruses responsible for the ongoing EVD epidemic should be fully susceptible to established antiviral strategies targeting GP and cellular entry factors. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Lack of transmission of mouse minute virus (MMV) from in vitro-produced embryos to recipients and pups due to the presence of cumulus cells during the in vitro fertilization process.

PubMed

Mahabir, E; Bulian, D; Needham, J; Schmidt, J

2009-09-01

The risk of transmission of mouse minute virus (MMV) to recipients of murine embryos arising from in vitro fertilization (IVF) of cumulus-enclosed oocytes (CEOs) or without cumulus cells (CDOs) in the presence of MMV-exposed (10(4) TCID(50) [mean tissue culture infective dose]/ml MMVp [prototype strain of MMV]) spermatozoa was evaluated. Also, the time after embryo transfer to detection of MMV antibody and the presence of MMV DNA in the mesenteric lymph nodes of recipients and pups were investigated. All mice were MMV free, but two seropositive recipients and four seropositive pups were found in the group with CDOs. With regard to the CEOs, two of 11 holding drops and five of 11 groups of embryos were MMV positive using PCR, while neither holding drops nor embryos carried infectious MMVp, as evidenced by the in vitro infectivity assay. From IVF with CDOs, five of 14 holding drops and four of nine groups of embryos were MMV positive, while one of 14 holding drops and no embryos carried infectious MMVp. When 10(5) cumulus cells were analyzed 5 h after exposure to 10(4) TCID(50)/ml MMVp, cells had an average titer of 10(4) TCID(50)/ml MMVp. The present data show that, in contrast to CDOs, 2-cell embryos from CEOs did not transmit infectious MMVp to the holding drops and to recipients. This observation is due to the presence of cumulus cells during the IVF process that reduce entry of MMV into the zona pellucida and absorb some of the virus. These data further confirm the efficacy of the IVF procedure in producing embryos that are free of infectious virus, leading to virus-free seronegative recipients and rederived pups.

Veterinary Safety's Conflicts in the EAEU

ERIC Educational Resources Information Center

Kalymbek, Bakytzhan; Shulanbekova, Gulmira K.; Madiyarova, Ainur S.; Mirambaeva, Gulnaz Zh.

2016-01-01

This article is devoted to the problem of veterinary safety of the countries under the Eurasian Economic Union. Animal health's measures are provided in order to prevent the entry and spread of infectious animal diseases, including common to humans and animals, as well as goods not conforming to the common veterinary and sanitary requirements.…

Cell entry by a novel European filovirus requires host endosomal cysteine proteases and Niemann-Pick C1

PubMed Central

Ng, Melinda; Ndungo, Esther; Jangra, Rohit K.; Cai, Yingyun; Postnikova, Elena; Radoshitzky, Sheli R.; Dye, John M.; de Arellano, Eva Ramírez; Negredo, Ana; Palacios, Gustavo; Kuhn, Jens H.; Chandran, Kartik

2014-01-01

Lloviu virus (LLOV), a phylogenetically divergent filovirus, is the proposed etiologic agent of die-offs of Schreiber’s long-fingered bats (Miniopterus schreibersii) in western Europe. Studies of LLOV remain limited because the infectious agent has not yet been isolated. Here, we generated a recombinant vesicular stomatitis virus expressing the LLOV spike glycoprotein (GP) and used it to show that LLOV GP resembles other filovirus GP proteins in structure and function. LLOV GP must be cleaved by endosomal cysteine proteases during entry, but is much more protease-sensitive than EBOV GP. The EBOV/MARV receptor, Niemann Pick C1 (NPC1), is also required for LLOV entry, and its second luminal domain is recognized with high affinity by a cleaved form of LLOV GP, suggesting that receptor binding would not impose a barrier to LLOV infection of humans and non-human primates. The use of NPC1 as an intracellular entry receptor may be a universal property of filoviruses. PMID:25310500

Syncytial Mutations Do Not Impair the Specificity of Entry and Spread of a Glycoprotein D Receptor-Retargeted Herpes Simplex Virus

PubMed Central

Okubo, Yu; Wakata, Aika; Suzuki, Takuma; Shibata, Tomoko; Ikeda, Hitomi; Yamaguchi, Miki; Cohen, Justus B.; Glorioso, Joseph C.; Tagaya, Mitsuo; Hamada, Hirofumi; Tahara, Hideaki

2016-01-01

ABSTRACT Membrane fusion, which is the key process for both initial cell entry and subsequent lateral spread of herpes simplex virus (HSV), requires the four envelope glycoproteins gB, gD, gH, and gL. Syncytial mutations, predominantly mapped to the gB and gK genes, confer hyperfusogenicity on HSV and cause multinucleated giant cells, termed syncytia. Here we asked whether interaction of gD with a cognate entry receptor remains indispensable for initiating membrane fusion of syncytial strains. To address this question, we took advantage of mutant viruses whose viral entry into cells relies on the uniquely specific interaction of an engineered gD with epidermal growth factor receptor (EGFR). We introduced selected syncytial mutations into gB and/or gK of the EGFR-retargeted HSV and found that these mutations, especially when combined, enabled formation of extensive syncytia by human cancer cell lines that express the target receptor; these syncytia were substantially larger than the plaques formed by the parental retargeted HSV strain. We assessed the EGFR dependence of entry and spread separately by using direct entry and infectious center assays, respectively, and we found that the syncytial mutations did not override the receptor specificity of the retargeted viruses at either stage. We discuss the implications of these results for the development of more effective targeted oncolytic HSV vectors. IMPORTANCE Herpes simplex virus (HSV) is investigated not only as a human pathogen but also as a promising agent for oncolytic virotherapy. We previously showed that both the initial entry and subsequent lateral spread of HSV can be retargeted to cells expressing tumor-associated antigens by single-chain antibodies fused to a receptor-binding-deficient envelope glycoprotein D (gD). Here we introduced syncytial mutations into the gB and/or gK gene of gD-retargeted HSVs to determine whether viral tropism remained dependent on the interaction of gD with the target receptor. Entry and spread profiles of the recombinant viruses indicated that gD retargeting does not abolish the hyperfusogenic activity of syncytial mutations and that these mutations do not eliminate the dependence of HSV entry and spread on a specific gD-receptor interaction. These observations suggest that syncytial mutations may be valuable for increasing the tumor-specific spreading of retargeted oncolytic HSV vectors. PMID:27707922

Measuring antiviral activity of benzimidazole molecules that alter IRES RNA structure with an infectious hepatitis C virus chimera expressing Renilla luciferase.

PubMed

Liu, Shuanghu; Nelson, Cassie A; Xiao, Li; Lu, Ling; Seth, Punit P; Davis, Darrell R; Hagedorn, Curt H

2011-01-01

Major progress has been made in developing infectious HCV cell culture systems and these systems have been useful in identifying novel HCV antivirals. However, more rapid and sensitive assays using infectious cell based HCV systems would facilitate the development of additional antivirals, including small molecules directed at unique targets such as the HCV RNA internal ribosomal entry site (IRES). We have found that the V3 region (28 aa) of NS5A of HCV JFH1 can be deleted from the genome with only modest effects on the titer of infectious virus produced in cell culture. Moreover, the V3 region can be replaced with the Renilla reniformis luciferase (Rluc) gene resulting in an infectious virus that stably expresses an NS5A-Rluc fusion protein. Infected cells cultured in 96-well plates provided a robust luciferase signal that accurately reflected the production of infectious virus. This infectious HCV reporter system was used to test the activity of three benzimidazole compounds that bind the HCV RNA IRES. Compounds in this chemical class of small molecules bind and alter the IRES RNA structure at low to sub-micromolar concentrations and interfere with viral replication. The current study shows that these compounds inhibit HCV replication in an infectious HCV cell culture system, defines their IC(50) in this system, and provides a platform for the rapid testing of next generation inhibitors. Copyright © 2010 Elsevier B.V. All rights reserved.

Measuring Antiviral Activity of Benzimidazole Molecules that Alter IRES RNA Structure with an Infectious Hepatitis C Virus Chimera Expressing Renilla Luciferase

PubMed Central

Liu, Shuanghu; Nelson, Cassie A.; Xiao, Li; Lu, Ling; Seth, Punit P.; Davis, Darrell R.; Hagedorn, Curt H.

2010-01-01

Major progress has been made in developing infectious HCV cell culture systems and these systems have been useful in identifying novel HCV antivirals. However, more rapid and sensitive assays using infectious cell based HCV systems would facilitate the development of additional antivirals, including small molecules directed at unique targets such as the HCV RNA internal ribosomal entry site (IRES). We have found that the V3 region (28 aa) of NS5A of HCV JFH1 can be deleted from the genome with only modest effects on the titer of infectious virus produced in cell culture. Moreover, the V3 region can be replaced with the Renilla reniformis luciferase (Rluc) gene resulting in an infectious virus that stably expresses an NS5A-Rluc fusion protein. Infected cells cultured in 96-well plates provided a robust luciferase signal that accurately reflected the production of infectious virus. This infectious HCV reporter system was used to test the activity of three benzimidazole compounds that bind the HCV RNA IRES. Compounds in this chemical class of small molecules bind and alter the IRES RNA structure at low to sub-micromolar concentrations and interfere with viral replication. The current study shows that these compounds inhibit HCV replication in an infectious HCV cell culture system, defines their IC50 in this system, and provides a platform for the rapid testing of next generation inhibitors. PMID:21075143

Hepatitis C Virus Strain-Dependent Usage of Apolipoprotein E Modulates Assembly Efficiency and Specific Infectivity of Secreted Virions.

PubMed

Weller, Romy; Hueging, Kathrin; Brown, Richard J P; Todt, Daniel; Joecks, Sebastian; Vondran, Florian W R; Pietschmann, Thomas

2017-09-15

Hepatitis C virus (HCV) is extraordinarily diverse and uses entry factors in a strain-specific manner. Virus particles associate with lipoproteins, and apolipoprotein E (ApoE) is critical for HCV assembly and infectivity. However, whether ApoE dependency is common to all HCV genotypes remains unknown. Therefore, we compared the roles of ApoE utilizing 10 virus strains from genotypes 1 through 7. ApoA and ApoC also support HCV assembly, so they may contribute to virus production in a strain-dependent fashion. Transcriptome sequencing (RNA-seq) revealed abundant coexpression of ApoE, ApoB, ApoA1, ApoA2, ApoC1, ApoC2, and ApoC3 in primary hepatocytes and in Huh-7.5 cells. Virus production was examined in Huh-7.5 cells with and without ApoE expression and in 293T cells where individual apolipoproteins (ApoE1, -E2, -E3, -A1, -A2, -C1, and -C3) were provided in trans All strains were strictly ApoE dependent. However, ApoE involvement in virus production was strain and cell type specific, because some HCV strains poorly produced infectious virus in ApoE-expressing 293T cells and because ApoE knockout differentially affected virus production of HCV strains in Huh-7.5 cells. ApoE allelic isoforms (ApoE2, -E3, and -E4) complemented virus production of HCV strains to comparable degrees. All tested strains assembled infectious progeny with ApoE in preference to other exchangeable apolipoproteins (ApoA1, -A2, -C1, and -C3). The specific infectivity of HCV particles was similar for 293T- and Huh-7.5-derived particles for most strains; however, it differed by more than 100-fold in some viruses. Collectively, this study reveals strain-dependent and host cell-dependent use of ApoE during HCV assembly. These differences relate to the efficacy of virus production and also to the properties of released virus particles and therefore govern viral fitness at the level of assembly and cell entry. IMPORTANCE Chronic HCV infections are a major cause of liver disease. HCV is highly variable, and strain-specific determinants modulate the response to antiviral therapy, the natural course of infection, and cell entry factor usage. Here we explored whether host factor dependency of HCV in particle assembly is modulated by strain-dependent viral properties. We showed that all examined HCV strains, which represent all seven known genotypes, rely on ApoE expression for assembly of infectious progeny. However, the degree of ApoE dependence is modulated in a strain-specific and cell type-dependent manner. This indicates that HCV strains differ in their assembly properties and host factor usage during assembly of infectious progeny. Importantly, these differences relate not only to the efficiency of virus production and release but also to the infectiousness of virus particles. Thus, strain-dependent features of HCV modulate ApoE usage, with implications for virus fitness at the level of assembly and cell entry. Copyright © 2017 Weller et al.

Single-Particle Tracking of Human Immunodeficiency Virus Type 1 Productive Entry into Human Primary Macrophages.

PubMed

Li, Qin; Li, Wei; Yin, Wen; Guo, Jia; Zhang, Zhi-Ping; Zeng, Dejun; Zhang, Xiaowei; Wu, Yuntao; Zhang, Xian-En; Cui, Zongqiang

2017-04-25

Macrophages are one of the major targets of human immunodeficiency virus (HIV-1), but the viral entry pathway remains poorly understood in these cells. Noninvasive virus labeling and single-virus tracking are effective tools for studying virus entry. Here, we constructed a quantum dot (QD)-encapsulated infectious HIV-1 particle to track viral entry at a single-particle level in live human primary macrophages. QDs were encapsulated in HIV-1 virions by incorporating viral accessory protein Vpr-conjugated QDs during virus assembly. With the HIV-1 particles encapsulating QDs, we monitored the early phase of viral infection in real time and observed that, during infection, HIV-1 was endocytosed in a clathrin-mediated manner; the particles were translocated into Rab5A-positive endosomes, and the core was released into the cytoplasm by viral envelope-mediated endosomal fusion. Drug inhibition assays verified that endosome fusion contributes to HIV-1 productive infection in primary macrophages. Additionally, we observed that a dynamic actin cytoskeleton is critical for HIV-1 entry and intracellular migration in primary macrophages. HIV-1 dynamics and infection could be blocked by multiple different actin inhibitors. Our study revealed a productive entry pathway in macrophages that requires both endosomal function and actin dynamics, which may assist in the development of inhibitors to block the HIV entry in macrophages.

The Structure of an Infectious Human Polyomavirus and Its Interactions with Cellular Receptors.

PubMed

Hurdiss, Daniel L; Frank, Martin; Snowden, Joseph S; Macdonald, Andrew; Ranson, Neil A

2018-06-05

BK polyomavirus (BKV) causes polyomavirus-associated nephropathy and hemorrhagic cystitis in immunosuppressed patients. These are diseases for which we currently have limited treatment options, but potential therapies could include pre-transplant vaccination with a multivalent BKV vaccine or therapeutics which inhibit capsid assembly or block attachment and entry into target cells. A useful tool in such efforts would be a high-resolution structure of the infectious BKV virion and how this interacts with its full repertoire of cellular receptors. We present the 3.4-Å cryoelectron microscopy structure of native, infectious BKV in complex with the receptor fragment of GT1b ganglioside. We also present structural evidence that BKV can utilize glycosaminoglycans as attachment receptors. This work highlights features that underpin capsid stability and provides a platform for rational design and development of urgently needed pharmacological interventions for BKV-associated diseases. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Functional Interplay Between Murine Leukemia Virus Glycogag, Serinc5, and Surface Glycoprotein Governs Virus Entry, with Opposite Effects on Gammaretroviral and Ebolavirus Glycoproteins.

PubMed

Ahi, Yadvinder S; Zhang, Shu; Thappeta, Yashna; Denman, Audrey; Feizpour, Amin; Gummuluru, Suryaram; Reinhard, Bjoern; Muriaux, Delphine; Fivash, Matthew J; Rein, Alan

2016-11-22

Gammaretroviruses, such as murine leukemia viruses (MLVs), encode, in addition to the canonical Gag, Pol, and Env proteins that will form progeny virus particles, a protein called "glycogag" (glycosylated Gag). MLV glycogag contains the entire Gag sequence plus an 88-residue N-terminal extension. It has recently been reported that glycogag, like the Nef protein of HIV-1, counteracts the antiviral effects of the cellular protein Serinc5. We have found, in agreement with prior work, that glycogag strongly enhances the infectivity of MLVs with some Env proteins but not those with others. In contrast, however, glycogag was detrimental to MLVs carrying Ebolavirus glycoprotein. Glycogag could be replaced, with respect to viral infectivity, by the unrelated S2 protein of equine infectious anemia virus. We devised an assay for viral entry in which virus particles deliver the Cre recombinase into cells, leading to the expression of a reporter. Data from this assay showed that both the positive and the negative effects of glycogag and S2 upon MLV infectivity are exerted at the level of virus entry. Moreover, transfection of the virus-producing cells with a Serinc5 expression plasmid reduced the infectivity and entry capability of MLV carrying xenotropic MLV Env, particularly in the absence of glycogag. Conversely, Serinc5 expression abrogated the negative effects of glycogag upon the infectivity and entry capability of MLV carrying Ebolavirus glycoprotein. As Serinc5 may influence cellular phospholipid metabolism, it seems possible that all of these effects on virus entry derive from changes in the lipid composition of viral membranes. Many murine leukemia viruses (MLVs) encode a protein called "glycogag." The function of glycogag is not fully understood, but it can assist HIV-1 replication in the absence of the HIV-1 protein Nef under some circumstances. In turn, Nef counteracts the cellular protein Serinc5. Glycogag enhances the infectivity of MLVs with some but not all MLV Env proteins (which mediate viral entry into the host cell upon binding to cell surface receptors). We now report that glycogag acts by enhancing viral entry and that, like Nef, glycogag antagonizes Serinc5. Surprisingly, the effects of glycogag and Serinc5 upon the entry and infectivity of MLV particles carrying an Ebolavirus glycoprotein are the opposite of those observed with the MLV Env proteins. The unrelated S2 protein of equine infectious anemia virus (EIAV) is functionally analogous to glycogag in our experiments. Thus, three retroviruses (HIV-1, MLV, and EIAV) have independently evolved accessory proteins that counteract Serinc5. Copyright © 2016 Ahi et al.

Staying alive: Vibrio cholerae’s cycle of environmental survival, transmission, and dissemination

PubMed Central

Jones, Christopher J.; Yildiz, Fitnat H.

2015-01-01

Infectious diseases kill nearly 9 million people annually. Bacterial pathogens are responsible for a large proportion of these diseases and the bacterial agents of pneumonia, diarrhea, and tuberculosis are leading causes of death and disability worldwide (1). Increasingly, the crucial role of non-host environments in the life cycle of bacterial pathogens is being recognized. Heightened scrutiny has been given to the biological processes impacting pathogen dissemination and survival in the natural environment, as these processes are essential for the transmission of pathogenic bacteria to new hosts. This chapter focuses on the model environmental pathogen, Vibrio cholerae, to describe recent advances in our understanding of how pathogens survive between hosts and highlight the processes necessary to support the cycle of environmental survival, transmission, and dissemination. We describe the physiological and molecular responses of V. cholerae to changing environmental conditions, focusing on its survival in aquatic reservoirs between hosts and its entry and exit from human hosts. PMID:27227302

State and Local Perspective on Implementation of the Centers for Disease Control and Prevention Dog Confinement Agreement.

PubMed

Zaganjor, I; Sinclair, J R; Coleman, M S

2015-12-01

The Centers for Disease Control and Prevention (CDC) works in conjunction with state, territorial, local and tribal agencies (STLTAs) to prevent the transmission of infectious agents. Issuance of confinement agreements using CDC Form 75.37 'Notice to Owners and Importers of Dogs' to importers of dogs that are not vaccinated or incompletely vaccinated against rabies is part of the agency's regulatory programme to prevent the entry of dogs infected with rabies. Although this is a regulatory programme that depends heavily on partnerships between CDC and STLTAs, CDC had never formally evaluated the acceptability of the confinement agreement process with these partners. Thus, a short survey of nine STLTAs was conducted to evaluate whether these partners have enough personnel and resources to implement the regulation and their general opinions of the confinement agreement process. The results illustrate that CDC partners are dissatisfied to some extent with the process, and there are multiple issues limiting their success in enforcing the regulation. © 2015 Blackwell Verlag GmbH.

Involvement of Clathrin-Mediated Endocytosis in Human Immunodeficiency Virus Type 1 Entry

PubMed Central

Daecke, Jessica; Fackler, Oliver T.; Dittmar, Matthias T.; Kräusslich, Hans-Georg

2005-01-01

Productive entry of human immunodeficiency virus (HIV) is believed to occur by direct fusion at the plasma membrane. Endocytic uptake of HIV particles has been observed in several studies but is considered to be nonproductive, leading to virus degradation in the lysosome. We show here that endocytosis contributes significantly to productive HIV entry in HeLa cells by using trans dominant-negative mutants of dynamin and Eps15. Inducible expression of a dominant-negative mutant of dynamin in a CD4-positive HeLa cell line reduced HIV infection by 40 to 80%. This effect was independent of the infectious dose and was observed for three different isolates. Analysis of reverse transcription products by real-time PCR and of virus entry by delivery of a virion-associated Vpr-β-lactamase fusion protein revealed a similar reduction, indicating that the block occurred at the entry stage. A strong reduction of HIV entry was also observed upon transient transfection of a different trans dominant-negative variant of dynamin, and this reduction correlated with the relative inhibition of transferrin endocytosis. Expression of a dominant-negative variant of Eps15, which is specific for clathrin-dependent endocytosis, reduced HIV entry in HeLa cells by ca 95%, confirming the role of endocytosis for productive infection. In contrast, no effect was observed for a dominant-negative variant of caveolin. We conclude that dynamin-dependent, clathrin-mediated endocytosis can lead to productive entry of HIV in HeLa cells, suggesting this pathway as an alternative route of virus entry. PMID:15650184

RESPIRATORY INFECTIONS RESEARCH IN AFGHANISTAN: BIBLIOMETRIC ANALYSIS WITH THE DATABASE PUBMED.

PubMed

Pilsczek, Florian H

2015-01-01

Infectious diseases research in a low-income country like Afghanistan is important. In this study an internet-based database Pubmed was used for bibliometric analysis of infectious diseases research activity. Research publications entries in PubMed were analysed according to number of publications, topic, publication type, and country of investigators. Between 2002-2011, 226 (77.7%) publications with the following research topics were identified: respiratory infections 3 (1.3%); parasites 8 (3.5%); diarrhoea 10 (4.4%); tuberculosis 10 (4.4%); human immunodeficiency virus (HIV) 11 (4.9%); multi-drug resistant bacteria (MDR) 18 (8.0%); polio 31 (13.7%); leishmania 31 (13.7%); malaria 46 (20.4%). From 2002-2011, 11 (4.9%) publications were basic science laboratory-based research studies. Between 2002-2011, 8 (3.5%) publications from Afghan institutions were identified. In conclusion, the internet-based database Pubmed can be consulted to collect data for guidance of infectious diseases research activity of low-income countries. The presented data suggest that infectious diseases research in Afghanistan is limited for respiratory infections research, has few studies conducted by Afghan institutions, and limited laboratory-based research contributions.

76 FR 37136 - Post-Entry Amendment (PEA) Processing Test: Modification, Clarification, and Extension

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

.... Customs and Border Protection's (CBP's) Post-Entry Amendment (PEA) Processing test, which allows the...: The Post-Entry Amendment (PEA) Processing test modification set forth in this document is effective...: Background I. Post-Entry Amendment Processing Test Program The Post-Entry Amendment (PEA) Processing test...

Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery

PubMed Central

van Dongen, Helena M.; Masoumi, Niala

2016-01-01

SUMMARY Extracellular vesicles (EVs) have emerged as crucial mediators of intercellular communication, being involved in a wide array of key biological processes. Eukaryotic cells, and also bacteria, actively release heterogeneous subtypes of EVs into the extracellular space, where their contents reflect their (sub)cellular origin and the physiologic state of the parent cell. Within the past 20 years, presumed subtypes of EVs have been given a rather confusing diversity of names, including exosomes, microvesicles, ectosomes, microparticles, virosomes, virus-like particles, and oncosomes, and these names are variously defined by biogenesis, physical characteristics, or function. The latter category, functions, in particular the transmission of biological signals between cells in vivo and how EVs control biological processes, has garnered much interest. EVs have pathophysiological properties in cancer, neurodegenerative disorders, infectious disease, and cardiovascular disease, highlighting possibilities not only for minimally invasive diagnostic applications but also for therapeutic interventions, like macromolecular drug delivery. Yet, in order to pursue therapies involving EVs and delivering their cargo, a better grasp of EV targeting is needed. Here, we review recent progress in understanding the molecular mechanisms underpinning EV uptake by receptor-ligand interactions with recipient cells, highlighting once again the overlap of EVs and viruses. Despite their highly heterogeneous nature, EVs require common viral entry pathways, and an unanticipated specificity for cargo delivery is being revealed. We discuss the challenges ahead in delineating specific roles for EV-associated ligands and cellular receptors. PMID:26935137

IHR (2005) Compliance: Laboratory Capacities and Biological Risks

DTIC Science & Technology

2014-08-01

Preparedness 6. Risk communication 7. Human resources 8. Laboratory Other obligations/Potential Hazards: 9. Points of entry 10. Zoonotic events 11. Food ...of personal protected equipment, 3) safe injection practices, 4) safe handling of potentially contaminated equipment and surfaces, and 5...Any public health event of international or national concern (infectious, zoonotic, food borne, chemical, radio nuclear, or due to unknown

From Exit to Entry: Long-term Survival and Transmission of Salmonella

PubMed Central

Waldner, Landon L.; MacKenzie, Keith D.; Köster,, Wolfgang; White, Aaron P.

2012-01-01

Salmonella spp. are a leading cause of human infectious disease worldwide and pose a serious health concern. While we have an improving understanding of pathogenesis and the host-pathogen interactions underlying the infection process, comparatively little is known about the survival of pathogenic Salmonella outside their hosts. This review focuses on three areas: (1) in vitro evidence that Salmonella spp. can survive for long periods of time under harsh conditions; (2) observations and conclusions about Salmonella persistence obtained from human outbreaks; and (3) new information revealed by genomic- and population-based studies of Salmonella and related enteric pathogens. We highlight the mechanisms of Salmonella persistence and transmission as an essential part of their lifecycle and a prerequisite for their evolutionary success as human pathogens. PMID:25436767

Analysis of Ebola Virus Entry Into Macrophages.

PubMed

Dahlmann, Franziska; Biedenkopf, Nadine; Babler, Anne; Jahnen-Dechent, Willi; Karsten, Christina B; Gnirß, Kerstin; Schneider, Heike; Wrensch, Florian; O'Callaghan, Christopher A; Bertram, Stephanie; Herrler, Georg; Becker, Stephan; Pöhlmann, Stefan; Hofmann-Winkler, Heike

2015-10-01

Ebolaviruses constitute a public health threat, particularly in Central and Western Africa. Host cell factors required for spread of ebolaviruses may serve as targets for antiviral intervention. Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. However, the factors used by ebolaviruses to invade macrophages, major viral targets, are poorly defined. Here, we show that mannose-specific lectins, TIM-1 and Axl augment entry into certain cell lines but do not contribute to Ebola virus (EBOV)-glycoprotein (GP)-driven transduction of macrophages. In contrast, expression of Mer, integrin αV, and NPC1 was required for efficient GP-mediated transduction and EBOV infection of macrophages. These results define cellular factors hijacked by EBOV for entry into macrophages and, considering that Mer and integrin αV promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Comparative Risk Analysis of Two Culicoides-Borne Diseases in Horses: Equine Encephalosis More Likely to Enter France than African Horse Sickness.

PubMed

Faverjon, C; Leblond, A; Lecollinet, S; Bødker, R; de Koeijer, A A; Fischer, E A J

2017-12-01

African horse sickness (AHS) and equine encephalosis (EE) are Culicoides-borne viral diseases that could have the potential to spread across Europe if introduced, thus being potential threats for the European equine industry. Both share similar epidemiology, transmission patterns and geographical distribution. Using stochastic spatiotemporal models of virus entry, we assessed and compared the probabilities of both viruses entering France via two pathways: importation of live-infected animals or importation of infected vectors. Analyses were performed for three consecutive years (2010-2012). Seasonal and regional differences in virus entry probabilities were the same for both diseases. However, the probability of EE entry was much higher than the probability of AHS entry. Interestingly, the most likely entry route differed between AHS and EE: AHS has a higher probability to enter through an infected vector and EE has a higher probability to enter through an infectious host. Consequently, different effective protective measures were identified by 'what-if' scenarios for the two diseases. The implementation of vector protection on all animals (equine and bovine) coming from low-risk regions before their importation was the most effective in reducing the probability of AHS entry. On the other hand, the most significant reduction in the probability of EE entry was obtained by the implementation of quarantine before import for horses coming from both EU and non-EU countries. The developed models can be useful to implement risk-based surveillance. © 2016 Blackwell Verlag GmbH.

Infectious mononucleosis at the United States Military Academy. A prospective study of a single class over four years.

PubMed

Hallee, T J; Evans, A S; Niederman, J C; Brooks, C M; Voegtly, j H

1974-09-01

A prospective study of EB virus infections was initiated in July, 1969 in the entering class of 1401 cadets, at the U.S. Military Academy at West Point, N.Y. and continued over 4 yr. On entry 63.5% possessed EBV antibody and 36.5 lacked EBV antibody. The rate of antibody prevalence varied with the geographic area from which the cadet originated.Except in two cadets already ill on first bleeding no evidence of clinical infectious mononucleosis (I.M.) occurred over the 4 yr period in the 890 cadets entering the Academy with EBV antibody. Among 437 cadets without antibody on entry, 54 or 12.4% were infected (seroconverted) in the freshman year; 15 of these had clinical I.M., 12 had suggestive I.M., and 39 had no known mono-like illness. The annual infection rates in susceptible cadets in the second, third, and fourth years were 24.4, 15.1, and 30.8 per 100, respectively. Of 201 cadets infected with EBV over 4 yr only 26.4% were manifested by heterophile positive clinical infectious mononucleosis. Overall, 46% of the 437 cadets entering without EBV antibody became infected over 40 mo of serologic observation; definite clinical infectious mononucleosis developed in 53 cadets, a clinical attack rate of 12.1 per 100 for 4 yr. The EBV infection rate among exposed and susceptible roommates of known cases was no higher than in roommates not so exposed.Elevations of EBV-specific and total IgM occurred during acute illness and disappeared in late convalescence. Total IgG and IgA levels were less commonly elevated. EBV-specific-IgM antibody was demonstrable during the acute illness but was absent 12 mo later. Analysis of EBV infection rates revealed no difference among persons of different ABO blood groups.

Infectious Mononucleosis at the United States Military Academy. A Prospective Study of a Single Class Over Four Years 1

PubMed Central

Hallee, T. James; Evans, Alfred S.; Niederman, James C.; Brooks, Charles M.; Voegtly, John H.

1974-01-01

A prospective study of EB virus infections was initiated in July, 1969 in the entering class of 1401 cadets, at the U.S. Military Academy at West Point, N.Y. and continued over 4 yr. On entry 63.5% possessed EBV antibody and 36.5 lacked EBV antibody. The rate of antibody prevalence varied with the geographic area from which the cadet originated. Except in two cadets already ill on first bleeding no evidence of clinical infectious mononucleosis (I.M.) occurred over the 4 yr period in the 890 cadets entering the Academy with EBV antibody. Among 437 cadets without antibody on entry, 54 or 12.4% were infected (seroconverted) in the freshman year; 15 of these had clinical I.M., 12 had suggestive I.M., and 39 had no known mono-like illness. The annual infection rates in susceptible cadets in the second, third, and fourth years were 24.4, 15.1, and 30.8 per 100, respectively. Of 201 cadets infected with EBV over 4 yr only 26.4% were manifested by heterophile positive clinical infectious mononucleosis. Overall, 46% of the 437 cadets entering without EBV antibody became infected over 40 mo of serologic observation; definite clinical infectious mononucleosis developed in 53 cadets, a clinical attack rate of 12.1 per 100 for 4 yr. The EBV infection rate among exposed and susceptible roommates of known cases was no higher than in roommates not so exposed. Elevations of EBV-specific and total IgM occurred during acute illness and disappeared in late convalescence. Total IgG and IgA levels were less commonly elevated. EBV-specific-IgM antibody was demonstrable during the acute illness but was absent 12 mo later. Analysis of EBV infection rates revealed no difference among persons of different ABO blood groups. PMID:4374836

Productive vs non-productive infection by cell-free Varicella zoster virus of human neurons derived from embryonic stem cells is dependent upon infectious viral dose

PubMed Central

Sloutskin, Anna; Kinchington, Paul R.; Goldstein, Ronald S.

2013-01-01

Varicella Zoster virus (VZV) productively infects humans causing varicella upon primary infection and herpes zoster upon reactivation from latency in neurons. In-vitro studies using cell-associated VZV infection have demonstrated productive VZV-infection, while a few recent studies of human neurons derived from stem cells incubated with cell-free, vaccine-derived VZV did not result in generation of infectious virus. In the present study, 90%-pure human embryonic stem cell-derived neurons were incubated with recombinant cell-free pOka-derived made with an improved method or with VZV vaccine. We found that cell-free pOka and vOka at higher multiplicities of infection elicited productive infection in neurons followed by spread of infection, cytopathic effect and release of infectious virus into the medium. These results further validate the use of this unlimited source of human neurons for studying unexplored aspects of VZV interaction with neurons such as entry, latency and reactivation. PMID:23769240

An infectious bat chimeric influenza virus harboring the entry machinery of a influenza A virus

PubMed Central

Juozapaitis, Mindaugas; Moreira, Étori Aguiar; Mena, Ignacio; Giese, Sebastian; Riegger, David; Pohlmann, Anne; Höper, Dirk; Zimmer, Gert; Beer, Martin; García-Sastre, Adolfo; Schwemmle, Martin

2017-01-01

In 2012 the complete genomic sequence of a new and potentially harmful influenza A-like virus from bats (H17N10) was identified. However, infectious influenza virus was neither isolated from infected bats nor reconstituted, impeding further characterization of this virus. Here we show the generation of an infectious chimeric virus containing six out of the eight bat virus genes, with the remaining two genes encoding the HA and NA proteins of a prototypic influenza A virus. This engineered virus replicates well in a broad range of mammalian cell cultures, human primary airway epithelial cells and mice, but poorly in avian cells and chicken embryos without further adaptation. Importantly, the bat chimeric virus is unable to reassort with other influenza A viruses. Although our data do not exclude the possibility of zoonotic transmission of bat influenza viruses into the human population, they indicate that multiple barriers exist that makes this an unlikely event. PMID:25055345

An infectious bat-derived chimeric influenza virus harbouring the entry machinery of an influenza A virus.

PubMed

Juozapaitis, Mindaugas; Aguiar Moreira, Étori; Mena, Ignacio; Giese, Sebastian; Riegger, David; Pohlmann, Anne; Höper, Dirk; Zimmer, Gert; Beer, Martin; García-Sastre, Adolfo; Schwemmle, Martin

2014-07-23

In 2012, the complete genomic sequence of a new and potentially harmful influenza A-like virus from bats (H17N10) was identified. However, infectious influenza virus was neither isolated from infected bats nor reconstituted, impeding further characterization of this virus. Here we show the generation of an infectious chimeric virus containing six out of the eight bat virus genes, with the remaining two genes encoding the haemagglutinin and neuraminidase proteins of a prototypic influenza A virus. This engineered virus replicates well in a broad range of mammalian cell cultures, human primary airway epithelial cells and mice, but poorly in avian cells and chicken embryos without further adaptation. Importantly, the bat chimeric virus is unable to reassort with other influenza A viruses. Although our data do not exclude the possibility of zoonotic transmission of bat influenza viruses into the human population, they indicate that multiple barriers exist that makes this an unlikely event.

Infectious disease health services for refugees and asylum seekers during a time of crisis: A scoping study of six European Union countries.

PubMed

Bozorgmehr, Kayvan; Samuilova, Mariya; Petrova-Benedict, Roumyana; Girardi, Enrico; Piselli, Pierluca; Kentikelenis, Alexander

2018-04-11

Systematic information on infectious disease services provided to refugees and asylum seekers in the European Union (EU) is sparse. We conducted a scoping study of experts in six EU countries in order to map health system responses related to infectious disease prevention and control among refugees and asylum seekers. We conducted 27 semi-structured in-depth interviews with first-line staff and health officials to collect information about existing guidelines and practices at each stage of reception in first-entry (Greece/Italy), transit (Croatia/Slovenia), and destination countries (Austria/Sweden). Thematic coding was used to perform a content analysis of interview material. Guidance on infectious disease screening and health assessments lack standardisation across and-partly-within countries. Data collection on notifiable infectious diseases is mainly reported to be performed by national public health institutions, but is not stratified by migrant status. Health-related information is not transferred in a standardized way between facilities within a single country. International exchange of medical information between countries along the migration route is irregular. Services were reported to be fragmented, and respondents mentioned no specific coordination bodies beyond health authorities at different levels. Infectious disease health services provided to refugees and asylum seekers lack standardisation in health assessments, data collection, transfer of health-related information and (partly) coordination. This may negatively affect health system performance including public health emergency preparedness. Copyright © 2018 Elsevier B.V. All rights reserved.

HIV-1 Env C2-V4 Diversification in a Slow-Progressor Infant Reveals a Flat but Rugged Fitness Landscape

PubMed Central

Smith, S. Abigail; Wood, Charles; West, John T.

2013-01-01

Human immunodeficiency virus type-1 (HIV-1) fitness has been associated with virus entry, a process mediated by the envelope glycoprotein (Env). We previously described Env genetic diversification in a Zambian, subtype C infected, slow-progressor child (1157i) in parallel with an evolving neutralizing antibody response. Because of the role the Variable-3 loop (V3) plays in transmission, cell tropism, neutralization sensitivity, and fitness, longitudinally isolated 1157i C2-V4 alleles were cloned into HIV-1NL4-3-eGFP and -DsRed2 infectious molecular clones. The fluorescent reporters allowed for dual-infection competitions between all patient-derived C2-V4 chimeras to quantify the effect of V3 diversification and selection on fitness. ‘Winners’ and ‘losers’ were readily discriminated among the C2-V4 alleles. Exceptional sensitivity for detection of subtle fitness differences was revealed through analysis of two alleles differing in a single synonymous amino acid. However, when the outcomes of N = 33 competitions were averaged for each chimera, the aggregate analysis showed that despite increasing diversification and divergence with time, natural selection of C2-V4 sequences in this individual did not appear to be producing a ‘survival of the fittest’ evolutionary pattern. Rather, we detected a relatively flat fitness landscape consistent with mutational robustness. Fitness outcomes were then correlated with individual components of the entry process. Env incorporation into particles correlated best with fitness, suggesting a role for Env avidity, as opposed to receptor/coreceptor affinity, in defining fitness. Nevertheless, biochemical analyses did not identify any step in HIV-1 entry as a dominant determinant of fitness. Our results lead us to conclude that multiple aspects of entry contribute to maintaining adequate HIV-1 fitness, and there is no surrogate analysis for determining fitness. The capacity for subtle polymorphisms in Env to nevertheless significantly impact viral fitness suggests fitness is best defined by head-to-head competition. PMID:23638182

Imaging host cell-Leishmania interaction dynamics implicates parasite motility, lysosome recruitment, and host cell wounding in the infection process.

PubMed

Forestier, Claire-Lise; Machu, Christophe; Loussert, Celine; Pescher, Pascale; Späth, Gerald F

2011-04-21

Leishmania donovani causes human visceral leishmaniasis. The parasite infectious cycle comprises extracellular flagellated promastigotes that proliferate inside the insect vector, and intracellular nonmotile amastigotes that multiply within infected host cells. Using primary macrophages infected with virulent metacyclic promastigotes and high spatiotemporal resolution microscopy, we dissect the dynamics of the early infection process. We find that motile promastigotes enter macrophages in a polarized manner through their flagellar tip and are engulfed into host lysosomal compartments. Persistent intracellular flagellar activity leads to reorientation of the parasite flagellum toward the host cell periphery and results in oscillatory parasite movement. The latter is associated with local lysosomal exocytosis and host cell plasma membrane wounding. These findings implicate lysosome recruitment followed by lysosome exocytosis, consistent with parasite-driven host cell injury, as key cellular events in Leishmania host cell infection. This work highlights the role of promastigote polarity and motility during parasite entry. Copyright © 2011 Elsevier Inc. All rights reserved.

Role for Telomerase in Listeria monocytogenes Infection

PubMed Central

Samba-Louaka, Ascel; Stavru, Fabrizia

2012-01-01

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the human telomerase complex. Growing evidence suggests that hTERT also contributes to the cell physiology independently of telomere elongation. However, its role in bacterial infection is unknown. Here we show that hTERT is critical for Listeria monocytogenes infection, as the depletion of hTERT impaired bacterial intracellular replication. In addition, we observed that L. monocytogenes caused a decrease in hTERT levels at early time points of the infectious process. This effect was mediated by the pore-forming toxin listeriolysin O (LLO) and did not require bacterial entry into host cells. Calcium influx through the LLO pores contributed to a proteasome-independent decrease in hTERT protein levels. Together, our data provide evidence that these bacteria trigger hTERT degradation, an event that is detrimental to bacterial replication. PMID:23006849

Inhibitors of COP-mediated Transport and Cholera Toxin Action Inhibit Simian Virus 40 Infection

PubMed Central

Richards, Ayanthi A.; Stang, Espen; Pepperkok, Rainer; Parton, Robert G.

2002-01-01

Simian virus 40 (SV40) is a nonenveloped virus that has been shown to pass from surface caveolae to the endoplasmic reticulum in an apparently novel infectious entry pathway. We now show that the initial entry step is blocked by brefeldin A and by incubation at 20°C. Subsequent to the entry step, the virus reaches a domain of the rough endoplasmic reticulum by an unknown pathway. This intracellular trafficking pathway is also brefeldin A sensitive. Infection is strongly inhibited by expression of GTP-restricted ADP-ribosylation factor 1 (Arf1) and Sar1 mutants and by microinjection of antibodies to βCOP. In addition, we demonstrate a potent inhibition of SV40 infection by the dipeptide N-benzoyl-oxycarbonyl-Gly-Phe-amide, which also inhibits late events in cholera toxin action. Our results identify novel inhibitors of SV40 infection and show that SV40 requires COPI- and COPII-dependent transport steps for successful infection. PMID:12006667

Cellular entry via an actin and clathrin-dependent route is required for Lv2 restriction of HIV-2.

PubMed

Harrison, I P; McKnight, A

2011-06-20

Lv2 is a human factor that restricts infection of some HIV-2 viruses after entry into particular target cells. HIV-2 MCR is highly susceptible to Lv2 whereas HIV-2 MCN is not. The block is after reverse transcription but prior to nuclear entry. The viral determinants for this restriction have been mapped to the HIV-2 envelope and the capsid genes. Our model of Lv2 restriction suggests that the route taken into a cell is important in determining whether a productive infection occurs. Here we characterised the infectious routes used by MCN and MCR using chemical compounds and molecular techniques to distinguish between potential pathways. Our results suggest that susceptible MCR can enter restrictive HeLa(CD4) cells via two pathways; a clathrin/AP2 mediated endocytic route that is sensitive to Lv2 restriction and an alternative, non-clathrin mediated route, which results in more efficient infection. Copyright © 2011 Elsevier Inc. All rights reserved.

Vpx complementation of 'non-macrophage tropic' R5 viruses reveals robust entry of infectious HIV-1 cores into macrophages.

PubMed

Mlcochova, Petra; Watters, Sarah A; Towers, Greg J; Noursadeghi, Mahdad; Gupta, Ravindra K

2014-03-21

It is now known that clinically derived viruses are most commonly R5 tropic with very low infectivity in macrophages. As these viruses utilize CD4 inefficiently, defective entry has been assumed to be the dominant restriction. The implication is that macrophages are not an important reservoir for the majority of circulating viruses. Macrophage infection by clinical transmitted/founder isolates was 10-100 and 30-450 fold less efficient as compared to YU-2 and BaL respectively. Vpx complementation augmented macrophage infection by non-macrophage tropic viruses to the level of infectivity observed for YU-2 in the absence of Vpx. Augmentation was evident even when Vpx was provided 24 hours post-infection. The entry defect was measured as 2.5-5 fold, with a further 3.5-10 fold block at strong stop and subsequent stages of reverse transcription as compared to YU-2. The overall block to infection was critically dependent on the mechanism of entry as demonstrated by rescue of infection after pseudotyping with VSV-G envelope. Reverse transcription in macrophages could not be enhanced using a panel of cytokines or lipopolysaccharide (LPS). Although the predominant block to clinical transmitted/founder viruses is post-entry, infectivity is determined by Env-CD4 interactions and can be rescued with VSV-G pseudotyping. This suggests a functional link between the optimal entry pathway taken by macrophage tropic viruses and downstream events required for reverse transcription. Consistent with a predominantly post-entry block, replication of R5 using viruses can be greatly enhanced by Vpx. We conclude therefore that entry is not the limiting step and that macrophages represent clinically relevant reservoirs for 'non-macrophage tropic' viruses.

Approved Antiviral Drugs over the Past 50 Years

PubMed Central

2016-01-01

SUMMARY Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2′-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2′-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide. PMID:27281742

Development of an infection screening system for entry inspection at airport quarantine stations using ear temperature, heart and respiration rates.

PubMed

Sun, Guanghao; Abe, Nobujiro; Sugiyama, Youhei; Nguyen, Quang Vinh; Nozaki, Kohei; Nakayama, Yosuke; Takei, Osamu; Hakozaki, Yukiya; Abe, Shigeto; Matsui, Takemi

2013-01-01

After the outbreak of severe acute respiratory syndrome (SARS) in 2003, many international airport quarantine stations conducted fever-based screening to identify infected passengers using infrared thermography for preventing global pandemics. Due to environmental factors affecting measurement of facial skin temperature with thermography, some previous studies revealed the limits of authenticity in detecting infectious symptoms. In order to implement more strict entry screening in the epidemic seasons of emerging infectious diseases, we developed an infection screening system for airport quarantines using multi-parameter vital signs. This system can automatically detect infected individuals within several tens of seconds by a neural-network-based discriminant function using measured vital signs, i.e., heart rate obtained by a reflective photo sensor, respiration rate determined by a 10-GHz non-contact respiration radar, and the ear temperature monitored by a thermography. In this paper, to reduce the environmental effects on thermography measurement, we adopted the ear temperature as a new screening indicator instead of facial skin. We tested the system on 13 influenza patients and 33 normal subjects. The sensitivity of the infection screening system in detecting influenza were 92.3%, which was higher than the sensitivity reported in our previous paper (88.0%) with average facial skin temperature.

Identification of a coumarin-based antihistamine-like small molecule as an anti-filoviral entry inhibitor.

PubMed

Cheng, Han; Schafer, Adam; Soloveva, Veronica; Gharaibeh, Dima; Kenny, Tara; Retterer, Cary; Zamani, Rouzbeh; Bavari, Sina; Peet, Norton P; Rong, Lijun

2017-09-01

Filoviruses, consisting of Ebola virus, Marburg virus and Cuevavirus, cause severe hemorrhagic fevers in humans with high mortality rates up to 90%. Currently, there is no approved vaccine or therapy available for the prevention and treatment of filovirus infection in humans. The recent 2013-2015 West African Ebola epidemic underscores the urgency to develop antiviral therapeutics against these infectious diseases. Our previous study showed that GPCR antagonists, particularly histamine receptor antagonists (antihistamines) inhibit Ebola and Marburg virus entry. In this study, we screened a library of 1220 small molecules with predicted antihistamine activity, identified multiple compounds with potent inhibitory activity against entry of both Ebola and Marburg viruses in human cancer cell lines, and confirmed their anti-Ebola activity in human primary cells. These small molecules target a late-stage of Ebola virus entry. Further structure-activity relationship studies around one compound (cp19) reveal the importance of the coumarin fused ring structure, especially the hydrophobic substituents at positions 3 and/or 4, for its antiviral activity, and this identified scaffold represents a favorable starting point for the rapid development of anti-filovirus therapeutic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Host-derived apolipoproteins play comparable roles with viral secretory proteins Erns and NS1 in the infectious particle formation of Flaviviridae

PubMed Central

Ono, Chikako; Shiokawa, Mai; Mori, Hiroyuki; Uemura, Kentaro; Yamamoto, Satomi; Okamoto, Toru; Suzuki, Ryosuke; Yoshii, Kentaro; Kurosu, Takeshi; Igarashi, Manabu; Aoki, Hiroshi; Sakoda, Yoshihiro

2017-01-01

Amphipathic α-helices of exchangeable apolipoproteins have shown to play crucial roles in the formation of infectious hepatitis C virus (HCV) particles through the interaction with viral particles. Among the Flaviviridae members, pestivirus and flavivirus possess a viral structural protein Erns or a non-structural protein 1 (NS1) as secretory glycoproteins, respectively, while Hepacivirus including HCV has no secretory glycoprotein. In case of pestivirus replication, the C-terminal long amphipathic α-helices of Erns are important for anchoring to viral membrane. Here we show that host-derived apolipoproteins play functional roles similar to those of virally encoded Erns and NS1 in the formation of infectious particles. We examined whether Erns and NS1 could compensate for the role of apolipoproteins in particle formation of HCV in apolipoprotein B (ApoB) and ApoE double-knockout Huh7 (BE-KO), and non-hepatic 293T cells. We found that exogenous expression of either Erns or NS1 rescued infectious particle formation of HCV in the BE-KO and 293T cells. In addition, expression of apolipoproteins or NS1 partially rescued the production of infectious pestivirus particles in cells upon electroporation with an Erns-deleted non-infectious RNA. As with exchangeable apolipoproteins, the C-terminal amphipathic α-helices of Erns play the functional roles in the formation of infectious HCV or pestivirus particles. These results strongly suggest that the host- and virus-derived secretory glycoproteins have overlapping roles in the viral life cycle of Flaviviridae, especially in the maturation of infectious particles, while Erns and NS1 also participate in replication complex formation and viral entry, respectively. Considering the abundant hepatic expression and liver-specific propagation of these apolipoproteins, HCV might have evolved to utilize them in the formation of infectious particles through deletion of a secretory viral glycoprotein gene. PMID:28644867

Detection of canine pneumovirus in dogs with canine infectious respiratory disease.

PubMed

Mitchell, Judy A; Cardwell, Jacqueline M; Renshaw, Randall W; Dubovi, Edward J; Brownlie, Joe

2013-12-01

Canine pneumovirus (CnPnV) was recently identified during a retrospective survey of kenneled dogs in the United States. In this study, archived samples from pet and kenneled dogs in the United Kingdom were screened for CnPnV to explore the relationship between exposure to CnPnV and the development of canine infectious respiratory disease (CIRD). Within the pet dog population, CnPnV-seropositive dogs were detected throughout the United Kingdom and Republic of Ireland, with an overall estimated seroprevalence of 50% (n = 314/625 dogs). In the kennel population, there was a significant increase in seroprevalence, from 26% (n = 56/215 dogs) on the day of entry to 93.5% (n = 201/215 dogs) after 21 days (P <0001). Dogs that were seronegative on entry but seroconverted while in the kennel were 4 times more likely to develop severe respiratory disease than those that did not seroconvert (P < 0.001), and dogs with preexisting antibodies to CnPnV on the day of entry were significantly less likely to develop respiratory disease than immunologically naive dogs (P < 0.001). CnPnV was detected in the tracheal tissues of 29/205 kenneled dogs. Detection was most frequent in dogs with mild to moderate respiratory signs and histopathological changes and in dogs housed for 8 to 14 days, which coincided with a significant increase in the risk of developing respiratory disease compared to the risk of those housed 1 to 7 days (P < 0.001). These findings demonstrate that CnPnV is present in the United Kingdom dog population; there is a strong association between exposure to CnPnV and CIRD in the kennel studied and a potential benefit in vaccinating against CnPnV as part of a wider disease prevention strategy.

Rotaviruses induce an early membrane permeabilization of MA104 cells and do not require a low intracellular Ca2+ concentration to initiate their replication cycle.

PubMed Central

Cuadras, M A; Arias, C F; López, S

1997-01-01

In this work, we found that rotavirus infection induces an early membrane permeabilization of MA104 cells and promotes the coentry of toxins, such as alpha-sarcin, into the cell. This cell permeability was shown to depend on infectious virus and was also shown to be virus dose dependent, with 10 infectious particles per cell being sufficient to achieve maximum permeability; transient, lasting no more than 15 min after virus entry and probably occurring concomitantly with virus penetration; and specific, since cells that are poorly permissive for rotavirus were not permeabilized. The rotavirus-mediated coentry of toxins was not blocked by the endocytosis inhibitors dansylcadaverine and cytochalasin D or by the vacuolar proton-ATPase inhibitor bafilomycin A1, suggesting that neither endocytocis nor an intraendosomal acidic pH or a proton gradient is required for permeabilization of the cells. Compounds that raise the intracellular concentration of calcium ([Ca2+]i) by different mechanisms, such as the calcium ionophores A23187 and ionomycin and the endoplasmic reticulum calcium-ATPase inhibitor thapsigargin, did not block the coentry of alpha-sarcin or affect the onset of viral protein synthesis, suggesting that a low [Ca2+]i is not essential for the initial steps of the virus life cycle. Since the entry of alpha-sarcin correlates with virus penetration in all parameters tested, the assay for permeabilization to toxins might be a useful tool for studying and characterizing the route of entry and the mechanism used by rotaviruses to traverse the cell membrane and initiate a productive replication cycle. PMID:9371563

Selective inhibitor of endosomal trafficking pathways exploited by multiple toxins and viruses

PubMed Central

Gillespie, Eugene J.; Ho, Chi-Lee C.; Balaji, Kavitha; Clemens, Daniel L.; Deng, Gang; Wang, Yao E.; Elsaesser, Heidi J.; Tamilselvam, Batcha; Gargi, Amandeep; Dixon, Shandee D.; France, Bryan; Chamberlain, Brian T.; Blanke, Steven R.; Cheng, Genhong; de la Torre, Juan Carlos; Brooks, David G.; Jung, Michael E.; Colicelli, John; Damoiseaux, Robert; Bradley, Kenneth A.

2013-01-01

Pathogenic microorganisms and toxins have evolved a variety of mechanisms to gain access to the host-cell cytosol and thereby exert virulent effects upon the host. One common mechanism of cellular entry requires trafficking to an acidified endosome, which promotes translocation across the host membrane. To identify small-molecule inhibitors that block this process, a library of 30,000 small molecules was screened for inhibitors of anthrax lethal toxin. Here we report that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone, the most active compound identified in the screen, inhibits intoxication by lethal toxin and blocks the entry of multiple other acid-dependent bacterial toxins and viruses into mammalian cells. This compound, which we named EGA, also delays lysosomal targeting and degradation of the EGF receptor, indicating that it targets host-membrane trafficking. In contrast, EGA does not block endosomal recycling of transferrin, retrograde trafficking of ricin, phagolysosomal trafficking, or phagosome permeabilization by Franciscella tularensis. Furthermore, EGA does not neutralize acidic organelles, demonstrating that its mechanism of action is distinct from pH-raising agents such as ammonium chloride and bafilomycin A1. EGA is a powerful tool for the study of membrane trafficking and represents a class of host-targeted compounds for therapeutic development to treat infectious disease. PMID:24191014

Effect of bovine lactoferrin on Chlamydia trachomatis infection and inflammation.

PubMed

Sessa, Rosa; Di Pietro, Marisa; Filardo, Simone; Bressan, Alessia; Rosa, Luigi; Cutone, Antimo; Frioni, Alessandra; Berlutti, Francesca; Paesano, Rosalba; Valenti, Piera

2017-02-01

Chlamydia trachomatis is an obligate, intracellular pathogen responsible for the most common sexually transmitted bacterial disease worldwide, causing acute and chronic infections. The acute infection is susceptible to antibiotics, whereas the chronic one needs prolonged therapies, thus increasing the risk of developing antibiotic resistance. Novel alternative therapies are needed. The intracellular development of C. trachomatis requires essential nutrients, including iron. Iron-chelating drugs inhibit C. trachomatis developmental cycle. Lactoferrin (Lf), a pleiotropic iron binding glycoprotein, could be a promising candidate against C. trachomatis infection. Similarly to the efficacy against other intracellular pathogens, bovine Lf (bLf) could both interfere with C. trachomatis entry into epithelial cells and exert an anti-inflammatory activity. In vitro and in vivo effects of bLf against C. trachomatis infectious and inflammatory process has been investigated. BLf inhibits C. trachomatis entry into host cells when incubated with cell monolayers before or at the moment of the infection and down-regulates IL-6/IL-8 synthesized by infected cells. Six out of 7 pregnant women asymptomatically infected by C. trachomatis, after 30 days of bLf intravaginal administration, were negative for C. trachomatis and showed a decrease of cervical IL-6 levels. This is the first time that the bLf protective effect against C. trachomatis infection has been demonstrated.

New generation of oral mucosal vaccines targeting dendritic cells

PubMed Central

Owen, Jennifer L.; Sahay, Bikash; Mohamadzadeh, Mansour

2013-01-01

As most infectious organisms gain entry at mucosal surfaces, there is a great deal of interest in developing vaccines that elicit effective mucosal immune responses against pathogen challenge. Targeted vaccination is one of the most effective methods available to prevent and control infectious diseases. Mucosal vaccines can offer lower costs, better accessibility, needle free delivery, and a higher capacity for mass immunizations during pandemics. Both local mucosal immunity and robust systemic responses can be achieved through mucosal vaccination. Recent progress in understanding the molecular and cellular components of the mucosal immune system have allowed for the development of a novel mucosal vaccine platform utilizing specific dendritic cell-targeting peptides and orally administered lactobacilli to elicit efficient antigen specific immune responses against infections, including B. anthracis in experimental models of disease. PMID:23835515

19 CFR 191.143 - Drawback entry.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRAWBACK Foreign-Built Jet Aircraft Engines Processed in the United States § 191.143 Drawback entry. (a) Filing of entry. Drawback entries covering these foreign-built jet aircraft engines shall be filed on Customs Form 7551, modified to show that the entry covers jet aircraft engines processed under...

19 CFR 191.143 - Drawback entry.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRAWBACK Foreign-Built Jet Aircraft Engines Processed in the United States § 191.143 Drawback entry. (a) Filing of entry. Drawback entries covering these foreign-built jet aircraft engines shall be filed on Customs Form 7551, modified to show that the entry covers jet aircraft engines processed under...

Escape of Actively Secreting Shigella flexneri from ATG8/LC3-Positive Vacuoles Formed during Cell-To-Cell Spread Is Facilitated by IcsB and VirA

PubMed Central

Sachse, Martin; Sansonetti, Philippe J.; Parsot, Claude

2015-01-01

ABSTRACT The enteropathogenic bacterium Shigella flexneri uses a type 3 secretion apparatus (T3SA) to transfer proteins dubbed translocators and effectors inside host cells, inducing bacterial uptake and subsequent lysis of the entry vacuole. Once in the cytoplasm, the outer membrane protein IcsA induces actin polymerization, enabling cytoplasmic movement and cell-to-cell spread of bacteria. During this infectious process, S. flexneri is targeted by ATG8/LC3. The effector IcsB was proposed to inhibit LC3 recruitment by masking a region of IcsA recognized by the autophagy pathway component ATG5. The effector VirA, a GTPase-activating protein (GAP) for Rab1, was also shown to prevent LC3 recruitment. However, the context of LC3 recruitment around S. flexneri is not fully understood. Here, we show that LC3 is recruited specifically around secreting bacteria that are still present in vacuoles formed during entry and cell-to-cell spread. While LC3 recruitment occurs around a small proportion of intracellular wild-type bacteria, the icsB, virA, and icsB virA mutants display incremental defaults in escape from LC3-positive vacuoles formed during cell-to-cell spread. Our results indicate that IcsB and VirA act synergistically to allow bacteria to escape from LC3-positive vacuoles by acting at or in the immediate vicinity of the vacuole membrane(s). We also demonstrate that LC3 is recruited around bacteria still present in the single-membrane entry vacuole, in a manner akin to that seen with LC3-associated phagocytosis. Our results indicate that LC3 recruitment occurs around bacteria still, or already, in membrane compartments formed during entry and cell-to-cell spread, and not around bacteria free in the cytoplasm. PMID:26015503

Role of mannose-6-phosphate receptors in herpes simplex virus entry into cells and cell-to-cell transmission.

PubMed Central

Brunetti, C R; Burke, R L; Hoflack, B; Ludwig, T; Dingwell, K S; Johnson, D C

1995-01-01

Herpes simplex virus (HSV) glycoprotein D (gD) is essential for virus entry into cells, is modified with mannose-6-phosphate (M-6-P), and binds to both the 275-kDa M-6-P receptor (MPR) and the 46-kDa MPR (C. R. Brunetti, R. L. Burke, S. Kornfeld, W. Gregory, K. S. Dingwell, F. Masiarz, and D. C. Johnson, J. Biol. Chem. 269:17067-17074, 1994). Since MPRs are found on the surfaces of mammalian cells, we tested the hypothesis that MPRs could serve as receptors for HSV during virus entry into cells. A soluble form of the 275-kDa MPR, derived from fetal bovine serum, inhibited HSV plaques on monkey Vero cells, as did polyclonal rabbit anti-MPR antibodies. In addition, the number and size of HSV plaques were reduced when cells were treated with bovine serum albumin conjugated with pentamannose-phosphate (PM-PO4-BSA), a bulky ligand which can serve as a high-affinity ligand for MPRs. These data imply that HSV can use MPRs to enter cells; however, other molecules must also serve as receptors for HSV because a reasonable fraction of virus could enter cells treated with even the highest concentrations of these inhibitors. Consistent with the possibility that there are other receptors, HSV produced the same number of plaques on MPR-deficient mouse fibroblasts as were produced on normal mouse fibroblasts, but there was no inhibition with PM-PO4-BSA with either of these embryonic mouse cells. Together, these results demonstrate that HSV does not rely solely on MPRs to enter cells, although MPRs apparently play some role in virus entry into some cell types and, perhaps, act as one of a number of cell surface molecules that can facilitate entry. We also found that HSV produced small plaques on human fibroblasts derived from patients with pseudo-Hurler's polydystrophy, cells in which glycoproteins are not modified with M-6-P residues and yet production of infectious HSV particles was not altered in the pseudo-Hurler cells. In addition, HSV plaque size was reduced by PM-PO4-BSA; therefore, it appears that M-6-P residues and MPRs are required for efficient transmission of HSV between cells, a process which differs in some respects from entry of exogenous virus particles. PMID:7745699

25-Hydroxycholesterol Inhibition of Lassa Virus Infection through Aberrant GP1 Glycosylation.

PubMed

Shrivastava-Ranjan, Punya; Bergeron, Éric; Chakrabarti, Ayan K; Albariño, César G; Flint, Mike; Nichol, Stuart T; Spiropoulou, Christina F

2016-12-20

Lassa virus (LASV) infection is a major public health concern due to high fatality rates and limited effective treatment. The interferon-stimulated gene cholesterol 25-hydroxylase (CH25H) encodes an enzyme that catalyzes the production of 25-hydroxycholesterol (25HC). 25HC is involved in regulating cholesterol biosynthesis and has recently been identified as a potent antiviral targeting enveloped virus entry. Here, we show a previously unrecognized role of CH25H in inhibiting LASV glycoprotein glycosylation and the production of infectious virus. Overexpression of CH25H or treatment with 25HC decreased LASV G1 glycoprotein N-glycan maturation and reduced the production of infectious LASV. Depletion of endogenous CH25H using small interfering RNA (siRNA) enhanced the levels of fully glycosylated G1 and increased infectious LASV production. Finally, LASV particles produced from 25HC-treated cells were found to be less infectious, to incorporate aberrantly glycosylated GP1 species, and to be defective in binding alpha-dystroglycan, an attachment and entry receptor. Our findings identify a novel role for CH25H in controlling LASV propagation and indicate that manipulation of the expression of CH25H or the administration of 25HC may be a useful anti-LASV therapy. Lassa fever is an acute viral hemorrhagic fever in humans caused by Lassa virus (LASV). No vaccine for LASV is currently available. Treatment is limited to the administration of ribavirin, which is only effective when given early in the course of illness. Cholesterol 25-hydroxylase (CH25H) is a recently identified interferon-stimulated gene (ISG); it encodes an enzyme that catalyzes the production of 25-hydroxycholesterol (25HC), which inhibits several viruses. Here, we identify a novel antiviral mechanism of 25HC that is dependent on inhibiting the glycosylation of Lassa virus (LASV) glycoprotein and reducing the infectivity of LASV as a means of suppressing viral replication. Since N-linked glycosylation is a critical feature of other enveloped-virus glycoproteins, 25HC may be a broad inhibitor of virus infectivity. Copyright © 2016 Shrivastava-Ranjan et al.

Infectious mononucleosis and its relationship to EB virus antibody. A joint investigation by university health physicians and P.H.L.S. laboratories.

PubMed

1971-12-11

In October 1969 tests made on 1,457 students entering English universities and colleges showed that 57% already possessed antibody to EB virus. The students without antibody in these initial tests were retested seven months later and by then 12% had acquired antibody. In about one-third of them the acquisition of antibody was not associated with any illness. In about 20% respiratory and other illness had occurred, but these symptoms were almost equally frequent in students who had not acquired antibody. Nearly half had developed infectious mononucleosis. In students in whom the acquisition of EB virus antibody was associated with the clinical and haematological manifestations of infectious mononucleosis the Paul-Bunnell test was almost invariably positive. In contrast, when these manifestations were not associated with the acquisition of EB virus antibody the Paul-Bunnell test was always negative.Tests for cytomegalovirus antibody were also made on the students at entry. The proportion of students with this antibody was much less (30%) and only a small proportion (1.4%) of those without antibody had acquired cytomegalovirus antibody seven months later. In the only patient in whom the acquisition of cytomegalovirus antibody alone was associated with the clinical and haematological features of infectious mononucleosis the Paul-Bunnell test was negative.

Retroviral proteases and their roles in virion maturation.

PubMed

Konvalinka, Jan; Kräusslich, Hans-Georg; Müller, Barbara

2015-05-01

Proteolytic processing of viral polyproteins is essential for retrovirus infectivity. Retroviral proteases (PR) become activated during or after assembly of the immature, non-infectious virion. They cleave viral polyproteins at specific sites, inducing major structural rearrangements termed maturation. Maturation converts retroviral enzymes into their functional form, transforms the immature shell into a metastable state primed for early replication events, and enhances viral entry competence. Not only cleavage at all PR recognition sites, but also an ordered sequence of cleavages is crucial. Proteolysis is tightly regulated, but the triggering mechanisms and kinetics and pathway of morphological transitions remain enigmatic. Here, we outline PR structures and substrate specificities focusing on HIV PR as a therapeutic target. We discuss design and clinical success of HIV PR inhibitors, as well as resistance development towards these drugs. Finally, we summarize data elucidating the role of proteolysis in maturation and highlight unsolved questions regarding retroviral maturation. Copyright © 2015 Elsevier Inc. All rights reserved.

Proteomics Tracing the Footsteps of Infectious Disease*

PubMed Central

Greco, Todd M.; Cristea, Ileana M.

2017-01-01

Every year, a major cause of human disease and death worldwide is infection with the various pathogens—viruses, bacteria, fungi, and protozoa—that are intrinsic to our ecosystem. In efforts to control the prevalence of infectious disease and develop improved therapies, the scientific community has focused on building a molecular picture of pathogen infection and spread. These studies have been aimed at defining the cellular mechanisms that allow pathogen entry into hosts cells, their replication and transmission, as well as the core mechanisms of host defense against pathogens. The past two decades have demonstrated the valuable implementation of proteomic methods in all these areas of infectious disease research. Here, we provide a perspective on the contributions of mass spectrometry and other proteomics approaches to understanding the molecular details of pathogen infection. Specifically, we highlight methods used for defining the composition of viral and bacterial pathogens and the dynamic interaction with their hosts in space and time. We discuss the promise of MS-based proteomics in supporting the development of diagnostics and therapies, and the growing need for multiomics strategies for gaining a systems view of pathogen infection. PMID:28163258

An evaluation of emergency guidelines issued by the World Health Organization in response to four infectious disease outbreaks.

PubMed

Norris, Susan L; Sawin, Veronica Ivey; Ferri, Mauricio; Raques Sastre, Laura; Porgo, Teegwendé V

2018-01-01

The production of high-quality guidelines in response to public health emergencies poses challenges for the World Health Organization (WHO). The urgent need for guidance and the paucity of structured scientific data on emerging diseases hinder the formulation of evidence-informed recommendations using standard methods and procedures. In the context of the response to recent public health emergencies, this project aimed to describe the information products produced by WHO and assess the quality and trustworthiness of a subset of these products classified as guidelines. We selected four recent infectious disease emergencies: outbreaks of avian influenza A-H1N1 virus (2009) and H7N9 virus (2013), Middle East respiratory syndrome coronavirus (MERS-CoV) (2013), and Ebola virus disease (EVD) (2014 to 2016). We analyzed the development and publication processes and evaluated the quality of emergency guidelines using AGREE-II. We included 175 information products of which 87 were guidelines. These products demonstrated variable adherence to WHO publication requirements including the listing of external contributors, management of declarations of interest, and entry into WHO's public database of publications. For guidelines, the methods for development were incompletely reported; WHO's quality assurance process was rarely used; systematic or other evidence reviews were infrequently referenced; external peer review was not performed; and they scored poorly with AGREE II, particularly for rigour of development and editorial independence. Our study suggests that WHO guidelines produced in the context of a public health emergency can be improved upon, helping to assure the trustworthiness and utility of WHO information products in future emergencies.

[Staphylococcal toxic shock syndrome at a chronic hemodialysis].

PubMed

Alaoui, Hassan; Belhadj, Ayoub; Aissaoui, Younes; Seddiki, Rachid; Zoubir, Mohamed; Bougalem, Mohamed

2017-01-01

Staphylococcal toxic shock syndrome is an acute and systemic infectious syndrome associated with the super-antigenic activity of staphylococcal toxins. It is a pathology that is rather rare but remains burdened with a considerable mortality despite the therapeutic management. The gateway is usually cutaneous with secondary bacteremic spread could be subject to preventive measures. We report the case of a rapidly fatal staphylococcal toxic shock, developed in a chronic hemodialysis whose entry from the arteriovenous fistula was suspected.

New generation of oral mucosal vaccines targeting dendritic cells.

PubMed

Owen, Jennifer L; Sahay, Bikash; Mohamadzadeh, Mansour

2013-12-01

As most infectious organisms gain entry at mucosal surfaces, there is a great deal of interest in developing vaccines that elicit effective mucosal immune responses against pathogen challenge. Targeted vaccination is one of the most effective methods available to prevent and control infectious diseases. Mucosal vaccines can offer lower costs, better accessibility, needle free delivery, and a higher capacity for mass immunizations during pandemics. Both local mucosal immunity and robust systemic responses can be achieved through mucosal vaccination. Recent progress in understanding the molecular and cellular components of the mucosal immune system have allowed for the development of a novel mucosal vaccine platform utilizing specific dendritic cell-targeting peptides and orally administered lactobacilli to elicit efficient antigen specific immune responses against infections, including Bacillus anthracis in experimental models of disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Using a Relational Database to Index Infectious Disease Information

PubMed Central

Brown, Jay A.

2010-01-01

Mapping medical knowledge into a relational database became possible with the availability of personal computers and user-friendly database software in the early 1990s. To create a database of medical knowledge, the domain expert works like a mapmaker to first outline the domain and then add the details, starting with the most prominent features. The resulting “intelligent database” can support the decisions of healthcare professionals. The intelligent database described in this article contains profiles of 275 infectious diseases. Users can query the database for all diseases matching one or more specific criteria (symptom, endemic region of the world, or epidemiological factor). Epidemiological factors include sources (patients, water, soil, or animals), routes of entry, and insect vectors. Medical and public health professionals could use such a database as a decision-support software tool. PMID:20623018

Electrostatic Architecture of the Infectious Salmon Anemia Virus (ISAV) Core Fusion Protein Illustrates a Carboxyl-Carboxylate pH Sensor.

PubMed

Cook, Jonathan D; Soto-Montoya, Hazel; Korpela, Markus K; Lee, Jeffrey E

2015-07-24

Segment 5, ORF 1 of the infectious salmon anemia virus (ISAV) genome, encodes for the ISAV F protein, which is responsible for viral-host endosomal membrane fusion during a productive ISAV infection. The entry machinery of ISAV is composed of a complex of the ISAV F and ISAV hemagglutinin esterase (HE) proteins in an unknown stoichiometry prior to receptor engagement by ISAV HE. Following binding of the receptor to ISAV HE, dissociation of the ISAV F protein from HE, and subsequent endocytosis, the ISAV F protein resolves into a fusion-competent oligomeric state. Here, we present a 2.1 Å crystal structure of the fusion core of the ISAV F protein determined at low pH. This structure has allowed us to unambiguously demonstrate that the ISAV entry machinery exhibits typical class I viral fusion protein architecture. Furthermore, we have determined stabilizing factors that accommodate the pH-dependent mode of ISAV transmission, and our structure has allowed the identification of a central coil that is conserved across numerous and varied post-fusion viral glycoprotein structures. We then discuss a mechanistic model of ISAV fusion that parallels the paramyxoviral class I fusion strategy wherein attachment and fusion are relegated to separate proteins in a similar fashion to ISAV fusion. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Porcine, murine and human sialoadhesin (Sn/Siglec-1/CD169): portals for porcine reproductive and respiratory syndrome virus entry into target cells.

PubMed

Van Breedam, Wander; Verbeeck, Mieke; Christiaens, Isaura; Van Gorp, Hanne; Nauwynck, Hans J

2013-09-01

Porcine sialoadhesin (pSn; a sialic acid-binding lectin) and porcine CD163 (pCD163) are molecules that facilitate infectious entry of porcine reproductive and respiratory syndrome virus (PRRSV) into alveolar macrophages. In this study, it was shown that murine Sn (mSn) and human Sn (hSn), like pSn, can promote PRRSV infection of pCD163-expressing cells. Intact sialic acid-binding domains are crucial, since non-sialic acid-binding mutants of pSn, mSn and hSn did not promote infection. Endodomain-deletion mutants of pSn, mSn and hSn promoted PRRSV infection less efficiently, but also showed markedly reduced expression levels, making further research into the potential role of the Sn endodomain in PRRSV receptor activity necessary. These data further complement our knowledge on Sn as an important PRRSV receptor, and suggest - in combination with other published data - that species differences in the main PRRSV entry mediators Sn and CD163 do not account for the strict host species specificity displayed by the virus.

19 CFR 142.16 - Entry summary documentation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry summary documentation. 142.16 Section 142.16... TREASURY (CONTINUED) ENTRY PROCESS Entry Summary Documentation § 142.16 Entry summary documentation. (a) Entry summary not filed at time of entry. When the entry documentation is filed before the entry summary...

Lipopolysaccharide-binding alkylpolyamine DS-96 inhibits Chlamydia trachomatis infection by blocking attachment and entry.

PubMed

Osaka, Ichie; Hefty, P Scott

2014-06-01

Vaginally delivered microbicides are being developed to offer women self-initiated protection against transmission of sexually transmitted infections such as Chlamydia trachomatis. A small molecule, DS-96, rationally designed for high affinity to Escherichia coli lipid A, was previously demonstrated to bind and neutralize lipopolysaccharide (LPS) from a wide variety of Gram-negative bacteria (D. Sil et al., Antimicrob. Agents Chemother. 51: 2811-2819, 2007, doi:10.1128/AAC.00200-07). Aside from the lack of the repeating O antigen, chlamydial lipooligosaccharide (LOS) shares general molecular architecture features with E. coli LPS. Importantly, the portion of lipid A where the interaction with DS-96 is expected to take place is well conserved between the two organisms, leading to the hypothesis that DS-96 inhibits Chlamydia infection by binding to LOS and compromising the function. In this study, antichlamydial activity of DS-96 was examined in cell culture. DS-96 inhibited the intercellular growth of Chlamydia in a dose-dependent manner and offered a high level of inhibition at a relatively low concentration (8 μM). The data also revealed that infectious elementary bodies (EBs) were predominantly blocked at the attachment step, as indicated by the reduced number of EBs associated with the host cell surface following pretreatment. Of those EBs that were capable of attachment, the vast majority was unable to gain entry into the host cell. Inhibition of EB attachment and entry by DS-96 suggests that Chlamydia LOS is critical to these processes during the developmental cycle. Importantly, given the low association of host toxicity previously reported by Sil et al., DS-96 is expected to perform well in animal studies as an active antichlamydial compound in a vaginal microbicide. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Environmental contaminant mixtures modulate in vitro influenza infection.

PubMed

Desforges, Jean-Pierre; Bandoro, Christopher; Shehata, Laila; Sonne, Christian; Dietz, Rune; Puryear, Wendy B; Runstadler, Jonathan A

2018-09-01

Environmental chemicals, particularly organochlorinated contaminants (OCs), are associated with a ranged of adverse health effects, including impairment of the immune system and antiviral immunity. Influenza A virus (IAV) is an infectious disease of major global public health concern and exposure to OCs can increase the susceptibility, morbidity, and mortality to disease. It is however unclear how pollutants are interacting and affecting the outcome of viral infections at the cellular level. In this study, we investigated the effects of a mixture of environmentally relevant OCs on IAV infectivity upon in vitro exposure in Madin Darby Canine Kidney (MDCK) cells and human lung epithelial cells (A549). Exposure to OCs reduced IAV infectivity in MDCK and A549 cells during both short (18-24h) and long-term (72h) infections at 0.05 and 0.5ppm, and effects were more pronounced in cells co-treated with OCs and IAV than pre-treated with OCs prior to IAV (p<0.001). Pre-treatment of host cells with OCs did not affect IAV cell surface attachment or entry. Visualization of IAV by transmission electron microscopy revealed increased envelope deformations and fewer intact virions during OC exposure. Taken together, our results suggest that disruption of IAV infection upon in vitro exposure to OCs was not due to host-cell effects influencing viral attachment and entry, but perhaps mediated by direct effects on viral particles or cellular processes involved in host-virus interactions. In vitro infectivity studies such as ours can shed light on the complex processes underlying host-pathogen-pollutant interactions. Copyright © 2018 Elsevier B.V. All rights reserved.

Betel quid use in relation to infectious disease outcomes in Cambodia.

PubMed

Singh, Pramil N; Natto, Zuhair; Yel, Daravuth; Job, Jayakaran; Knutsen, Synnove

2012-04-01

The habitual chewing of betel quid (areca nut, betel leaf, tobacco) is estimated to occur among 600 million persons in Asia and the Asia-Pacific Region. Emerging data from rural Asia indicate that the betel quid is part of traditional medicine practices that promote its use for a wide range of ailments, including infectious disease. In the present study, we examined the association between betel quid, traditional medicine, and infectious disease outcomes. For the purpose of a nationwide, interviewer-administered, cross-sectional survey of tobacco use (including betel quid), we conducted a stratified three-stage cluster sampling of 13 988 adults aged 18 years and older from all provinces of Cambodia. We found an association between the intensity of betel quid use and HIV/AIDS (odds ratio (OR) 2.06, 95% CI 1.09-3.89), dengue fever (OR 2.40, 95% CI 1.55-2.72), tuberculosis (OR 1.50, 95% CI 0.96-2.36), and typhoid (OR 1.48, 95% CI 0.95-2.30). These associations were even stronger in women - the primary users of betel quid in Cambodia. Multivariable analyses that controlled for age, gender, income, education, urban versus rural dwelling, receiving care from traditional medicine practitioners, and cigarette smoking did not alter the betel quid-infectious disease association. Our findings raise the possibility of a role of betel quid use in the transmission of infectious disease through pathways such as immunosuppression, oral route of entry for a pathogen (i.e., through injury to the oral mucosa), and contamination (i.e., fecal-oral) of the betel quid ingredients. Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Skin mucus of Cyprinus carpio inhibits cyprinid herpesvirus 3 binding to epidermal cells

PubMed Central

2011-01-01

Cyprinid herpesvirus 3 (CyHV-3) is the aetiological agent of a mortal and highly contagious disease in common and koi carp. The skin is the major portal of entry of CyHV-3 in carp after immersion in water containing the virus. In the present study, we used in vivo bioluminescence imaging to investigate the effect of skin mucus removal and skin epidermis lesion on CyHV-3 entry. Physical treatments inducing removal of the mucus up to complete erosion of the epidermis were applied on a defined area of carp skin just before inoculation by immersion in infectious water. CyHV-3 entry in carp was drastically enhanced on the area of the skin where the mucus was removed with or without associated epidermal lesion. To investigate whether skin mucus inhibits CyHV-3 binding to epidermal cells, tail fins with an intact mucus layer or without mucus were inoculated ex vivo. While electron microscopy examination revealed numerous viral particles bound on the fins inoculated after mucus removal, no particle could be detected after infection of mucus-covered fins. Finally, anti-CyHV-3 neutralising activity of mucus extract was tested in vitro. Incubation of CyHV-3 with mucus extract reduced its infectivity in a dose dependent manner. The present study demonstrates that skin mucus removal and epidermal lesions enhance CyHV-3 entry in carp. It highlights the role of fish skin mucus as an innate immune protection against viral epidermal entry. PMID:21816061

Branching processes in disease epidemics

NASA Astrophysics Data System (ADS)

Singh, Sarabjeet

Branching processes have served as a model for chemical reactions, biological growth processes and contagion (of disease, information or fads). Through this connection, these seemingly different physical processes share some common universalities that can be elucidated by analyzing the underlying branching process. In this thesis, we focus on branching processes as a model for infectious diseases spreading between individuals belonging to different populations. The distinction between populations can arise from species separation (as in the case of diseases which jump across species) or spatial separation (as in the case of disease spreading between farms, cities, urban centers, etc). A prominent example of the former is zoonoses -- infectious diseases that spill from animals to humans -- whose specific examples include Nipah virus, monkeypox, HIV and avian influenza. A prominent example of the latter is infectious diseases of animals such as foot and mouth disease and bovine tuberculosis that spread between farms or cattle herds. Another example of the latter is infectious diseases of humans such as H1N1 that spread from one city to another through migration of infectious hosts. This thesis consists of three main chapters, an introduction and an appendix. The introduction gives a brief history of mathematics in modeling the spread of infectious diseases along with a detailed description of the most commonly used disease model -- the Susceptible-Infectious-Recovered (SIR) model. The introduction also describes how the stochastic formulation of the model reduces to a branching process in the limit of large population which is analyzed in detail. The second chapter describes a two species model of zoonoses with coupled SIR processes and proceeds into the calculation of statistics pertinent to cross species infection using multitype branching processes. The third chapter describes an SIR process driven by a Poisson process of infection spillovers. This is posed as a model of infectious diseases where a `reservoir' of infection exists that infects a susceptible host population at a constant rate. The final chapter of the thesis describes a general framework of modeling infectious diseases in a network of populations using multitype branching processes.

Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2

PubMed Central

Reinke, Lennart Michel; Hartleib, Anika; Nehlmeier, Inga; Gierer, Stefanie; Hoffmann, Markus; Hofmann-Winkler, Heike; Winkler, Michael

2017-01-01

The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates viral entry into target cells. Cleavage and activation of SARS S by a host cell protease is essential for infectious viral entry and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease TMPRSS2 cleaves and activates SARS S in cell culture and potentially also in the infected host. Here, we investigated which determinants in SARS S control cleavage and activation by TMPRSS2. We found that SARS S residue R667, a previously identified trypsin cleavage site, is also required for S protein cleavage by TMPRSS2. The cleavage fragments produced by trypsin and TMPRSS2 differed in their decoration with N-glycans, suggesting that these proteases cleave different SARS S glycoforms. Although R667 was required for SARS S cleavage by TMPRSS2, this residue was dispensable for TMPRSS2-mediated S protein activation. Conversely, residue R797, previously reported to be required for SARS S activation by trypsin, was dispensable for S protein cleavage but required for S protein activation by TMPRSS2. Collectively, these results show that different residues in SARS S control cleavage and activation by TMPRSS2, suggesting that these processes are more complex than initially appreciated. PMID:28636671

Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2.

PubMed

Reinke, Lennart Michel; Spiegel, Martin; Plegge, Teresa; Hartleib, Anika; Nehlmeier, Inga; Gierer, Stefanie; Hoffmann, Markus; Hofmann-Winkler, Heike; Winkler, Michael; Pöhlmann, Stefan

2017-01-01

The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates viral entry into target cells. Cleavage and activation of SARS S by a host cell protease is essential for infectious viral entry and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease TMPRSS2 cleaves and activates SARS S in cell culture and potentially also in the infected host. Here, we investigated which determinants in SARS S control cleavage and activation by TMPRSS2. We found that SARS S residue R667, a previously identified trypsin cleavage site, is also required for S protein cleavage by TMPRSS2. The cleavage fragments produced by trypsin and TMPRSS2 differed in their decoration with N-glycans, suggesting that these proteases cleave different SARS S glycoforms. Although R667 was required for SARS S cleavage by TMPRSS2, this residue was dispensable for TMPRSS2-mediated S protein activation. Conversely, residue R797, previously reported to be required for SARS S activation by trypsin, was dispensable for S protein cleavage but required for S protein activation by TMPRSS2. Collectively, these results show that different residues in SARS S control cleavage and activation by TMPRSS2, suggesting that these processes are more complex than initially appreciated.

Infections Complicating Orthotopic Liver Transplantation

PubMed Central

Schröter, Gerhard P. J.; Hoelscher, Manfred; Putnam, Charles W.; Porter, Kendrick A.; Hansbrough, John F.; Starzl, Thomas E.

2011-01-01

In 93 recipients of 102 orthotopic liver homografts, the incidence of bacteremia or fungemia exceeded 70%. The graft itself was usually an entry site for systemic infection after both immunologic and nonimmunologic parenchymal injury, especially if there was defective biliary drainage. The role of the homograft itself as the special infectious risk factor has prompted increased use of defunctionalized jejunal Roux limbs to reduce graft contamination. It has also stimulated very aggressive postoperative diagnostic efforts to rule out remedial mechanical complications of the transplant. PMID:793568

Tannic Acid Inhibits Hepatitis C Virus Entry into Huh7.5 Cells

PubMed Central

Hagedorn, Curt H.

2015-01-01

Chronic infection with the hepatitis C virus (HCV) is a cause of cirrhosis and hepatocellular carcinoma worldwide. Although antiviral therapy has dramatically improved recently, a number of patients remain untreated and some do not clear infection with treatment. Viral entry is an essential step in initiating and maintaining chronic HCV infections. One dramatic example of this is the nearly 100% infection of newly transplanted livers in patients with chronic hepatitis C. HCV entry inhibitors could play a critical role in preventing HCV infection of newly transplanted livers. Tannic acid, a polymer of gallic acid and glucose molecules, is a plant-derived polyphenol that defends some plants from insects and microbial infections. It has been shown to have a variety of biological effects, including antiviral activity, and is used as a flavoring agent in foods and beverages. In this study, we demonstrate that tannic acid is a potent inhibitor of HCV entry into Huh7.5 cells at low concentrations (IC50 5.8 μM). It also blocks cell-to-cell spread in infectious HCV cell cultures, but does not inhibit HCV replication following infection. Moreover, experimental results indicate that tannic acid inhibits an early step of viral entry, such as the docking of HCV at the cell surface. Gallic acid, tannic acid’s structural component, did not show any anti-HCV activity including inhibition of HCV entry or replication at concentrations up to 25 μM. It is possible the tannin structure is related on the effect on HCV inhibition. Tannic acid, which is widely distributed in plants and foods, has HCV antiviral activity in cell culture at low micromolar concentrations, may provide a relative inexpensive adjuvant to direct-acting HCV antivirals and warrants future investigation. PMID:26186636

Functional Interplay Between Murine Leukemia Virus Glycogag, Serinc5, and Surface Glycoprotein Governs Virus Entry, with Opposite Effects on Gammaretroviral and Ebolavirus Glycoproteins

PubMed Central

Ahi, Yadvinder S.; Zhang, Shu; Thappeta, Yashna; Denman, Audrey; Feizpour, Amin; Reinhard, Bjoern; Muriaux, Delphine; Fivash, Matthew J.

2016-01-01

ABSTRACT Gammaretroviruses, such as murine leukemia viruses (MLVs), encode, in addition to the canonical Gag, Pol, and Env proteins that will form progeny virus particles, a protein called “glycogag” (glycosylated Gag). MLV glycogag contains the entire Gag sequence plus an 88-residue N-terminal extension. It has recently been reported that glycogag, like the Nef protein of HIV-1, counteracts the antiviral effects of the cellular protein Serinc5. We have found, in agreement with prior work, that glycogag strongly enhances the infectivity of MLVs with some Env proteins but not those with others. In contrast, however, glycogag was detrimental to MLVs carrying Ebolavirus glycoprotein. Glycogag could be replaced, with respect to viral infectivity, by the unrelated S2 protein of equine infectious anemia virus. We devised an assay for viral entry in which virus particles deliver the Cre recombinase into cells, leading to the expression of a reporter. Data from this assay showed that both the positive and the negative effects of glycogag and S2 upon MLV infectivity are exerted at the level of virus entry. Moreover, transfection of the virus-producing cells with a Serinc5 expression plasmid reduced the infectivity and entry capability of MLV carrying xenotropic MLV Env, particularly in the absence of glycogag. Conversely, Serinc5 expression abrogated the negative effects of glycogag upon the infectivity and entry capability of MLV carrying Ebolavirus glycoprotein. As Serinc5 may influence cellular phospholipid metabolism, it seems possible that all of these effects on virus entry derive from changes in the lipid composition of viral membranes. PMID:27879338

Infectious Mononucleosis and its Relationship to EB Virus Antibody: A JOINT INVESTIGATION BY UNIVERSITY HEALTH PHYSICIANS AND P.H.L.S. LABORATORIES*

PubMed Central

1971-01-01

In October 1969 tests made on 1,457 students entering English universities and colleges showed that 57% already possessed antibody to EB virus. The students without antibody in these initial tests were retested seven months later and by then 12% had acquired antibody. In about one-third of them the acquisition of antibody was not associated with any illness. In about 20% respiratory and other illness had occurred, but these symptoms were almost equally frequent in students who had not acquired antibody. Nearly half had developed infectious mononucleosis. In students in whom the acquisition of EB virus antibody was associated with the clinical and haematological manifestations of infectious mononucleosis the Paul-Bunnell test was almost invariably positive. In contrast, when these manifestations were not associated with the acquisition of EB virus antibody the Paul-Bunnell test was always negative. Tests for cytomegalovirus antibody were also made on the students at entry. The proportion of students with this antibody was much less (30%) and only a small proportion (1·4%) of those without antibody had acquired cytomegalovirus antibody seven months later. In the only patient in whom the acquisition of cytomegalovirus antibody alone was associated with the clinical and haematological features of infectious mononucleosis the Paul-Bunnell test was negative. PMID:4332464

Analysis of HSV viral reactivation in explants of sensory neurons

PubMed Central

Turner, Anne-Marie W.; Kristie, Thomas M.

2014-01-01

As with all Herpesviruses, Herpes simplex virus (HSV) has both a lytic replication phase and a latency-reactivation cycle. During lytic replication, there is an ordered cascade of viral gene expression that leads to the synthesis of infectious viral progeny. In contrast, latency is characterized by the lack of significant lytic gene expression and the absence of infectious virus. Reactivation from latency is characterized by the re-entry of the virus into the lytic replication cycle and the production of recurrent disease. This unit describes the establishment of the mouse sensory neuron model of HSV-1 latency-reactivation as a useful in vivo system for the analysis of mechanisms involved in latency and reactivation. Assays including the determination of viral yields, immunohistochemical/immunofluorescent detection of viral antigens, and mRNA quantitation are used in experiments designed to investigate the network of cellular and viral proteins regulating HSV-1 lytic infection, latency, and reactivation. PMID:25367271

[Neurological complications among patients with zoster hospitalized in Department of Infectious Diseases in Cracow in 2001-2006].

PubMed

Biesiada, Grazyna; Czepiel, Jacek; Sobczyk-Krupiarz, Iwona; Mach, Tomasz; Garlicki, Aleksander

2010-01-01

Herpes zoster is an infectious disease caused by varicella zoster virus (VZV). After replication at the place of entry, VZV spreads via the blood into the skin and mucosa, causing the varicella. From these regions VZV migrates into the sensory ganglia where it establishes a latent infection. The aim of our study was to analyze the localization of the skin changes and correlations of neurological complications among patient with zoster. We have reviewed medical documentation of the 67 patients with herpes zoster, hospitalized in our Department during the years 2001-2006. We have studied localization of the herpes zoster changes and frequency of neurological complications among these patients. Neuralgia was less intensive and last shorter time, when antiviral treatment had been started earlier. Neuralgia, meningitis, encephalitis and complications of the eye zoster were present more often among patients over 65 years old.

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

Khachatoorian, Ronik, E-mail: RnKhch@ucla.edu; Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, California, CA; Arumugaswami, Vaithilingaraja, E-mail: VArumugaswami@mednet.ucla.edu

We have previously demonstrated that quercetin, a bioflavonoid, blocks hepatitis C virus (HCV) proliferation by inhibiting NS5A-driven internal ribosomal entry site (IRES)-mediated translation of the viral genome. Here, we investigate the mechanisms of antiviral activity of quercetin and six additional bioflavonoids. We demonstrate that catechin, naringenin, and quercetin possess significant antiviral activity, with no associated cytotoxicity. Infectious virion secretion was not significantly altered by these bioflavonoids. Catechin and naringenin demonstrated stronger inhibition of infectious virion assembly compared to quercetin. Quercetin markedly blocked viral translation whereas catechin and naringenin demonstrated mild activity. Similarly quercetin completely blocked NS5A-augmented IRES-mediated translation in anmore » IRES reporter assay, whereas catechin and naringenin had only a mild effect. Moreover, quercetin differentially inhibited HSP70 induction compared to catechin and naringenin. Thus, the antiviral activity of these bioflavonoids is mediated through different mechanisms. Therefore combination of these bioflavonoids may act synergistically against HCV.« less

Emerging technologies in point-of-care molecular diagnostics for resource-limited settings.

PubMed

Peeling, Rosanna W; McNerney, Ruth

2014-06-01

Emerging molecular technologies to diagnose infectious diseases at the point at which care is delivered have the potential to save many lives in developing countries where access to laboratories is poor. Molecular tests are needed to improve the specificity of syndromic management, monitor progress towards disease elimination and screen for asymptomatic infections with the goal of interrupting disease transmission and preventing long-term sequelae. In simplifying laboratory-based molecular assays for use at point-of-care, there are inevitable compromises between cost, ease of use and test performance. Despite significant technological advances, many challenges remain for the development of molecular diagnostics for resource-limited settings. There needs to be more advocacy for these technologies to be applied to infectious diseases, increased efforts to lower the barriers to market entry through streamlined and harmonized regulatory approaches, faster policy development for adoption of new technologies and novel financing mechanisms to enable countries to scale up implementation.

Cross-cultural re-entry for missionaries: a new application for the Dual Process Model.

PubMed

Selby, Susan; Clark, Sheila; Braunack-Mayer, Annette; Jones, Alison; Moulding, Nicole; Beilby, Justin

Nearly half a million foreign aid workers currently work worldwide, including over 140,000 missionaries. During re-entry these workers may experience significant psychological distress. This article positions previous research about psychological distress during re-entry, emphasizing loss and grief. At present there is no identifiable theoretical framework to provide a basis for assessment, management, and prevention of re-entry distress in the clinical setting. The development of theoretical concepts and frameworks surrounding loss and grief including the Dual Process Model (DPM) are discussed. All the parameters of the DPM have been shown to be appropriate for the proposed re-entry model, the Dual Process Model applied to Re-entry (DPMR). It is proposed that the DPMR is an appropriate framework to address the processes and strategies of managing re-entry loss and grief. Possible future clinical applications and limitations of the proposed model are discussed. The DPMR is offered for further validation and use in clinical practice.

Spatial and temporal variation in evacuee risk perception throughout the evacuation and return-entry process.

PubMed

Siebeneck, Laura K; Cova, Thomas J

2012-09-01

Developing effective evacuation and return-entry plans requires understanding the spatial and temporal dimensions of risk perception experienced by evacuees throughout a disaster event. Using data gathered from the 2008 Cedar Rapids, Iowa Flood, this article explores how risk perception and location influence evacuee behavior during the evacuation and return-entry process. Three themes are discussed: (1) the spatial and temporal characteristics of risk perception throughout the evacuation and return-entry process, (2) the relationship between risk perception and household compliance with return-entry orders, and (3) the role social influences have on the timing of the return by households. The results indicate that geographic location and spatial variation of risk influenced household risk perception and compliance with return-entry plans. In addition, sociodemographic characteristics influenced the timing and characteristics of the return groups. The findings of this study advance knowledge of evacuee behavior throughout a disaster and can inform strategies used by emergency managers throughout the evacuation and return-entry process. © 2012 Society for Risk Analysis.

Rapid Dissemination of SIV Follows Multisite Entry after Rectal Inoculation

PubMed Central

Prétet, Jean-Luc; Michel-Salzat, Alice; Messent, Valérie; Bogdanova, Anna; Couëdel-Courteille, Anne; Souil, Evelyne; Cheynier, Rémi; Butor, Cécile

2011-01-01

Receptive ano-rectal intercourse is a major cause of HIV infection in men having sex with men and in heterosexuals. Current knowledge of the mechanisms of entry and dissemination during HIV rectal transmission is scarce and does not allow the development of preventive strategies. We investigated the early steps of rectal infection in rhesus macaques inoculated with the pathogenic isolate SIVmac251 and necropsied four hours to nine days later. All macaques were positive for SIV. Control macaques inoculated with heat-inactivated virus were consistently negative for SIV. SIV DNA was detected in the rectum as early as four hours post infection by nested PCR for gag in many laser-microdissected samples of lymphoid aggregates and lamina propria but never in follicle-associated epithelium. Scarce SIV antigen positive cells were observed by immunohistofluorescence in the rectum, among intraepithelial and lamina propria cells as well as in clusters in lymphoid aggregates, four hours post infection and onwards. These cells were T cells and non-T cells that were not epithelial cells, CD68+ macrophages, DC-SIGN+ cells or fascin+ dendritic cells. DC-SIGN+ cells carried infectious virus. Detection of Env singly spliced mRNA in the mucosa by nested RT-PCR indicated ongoing viral replication. Strikingly, four hours post infection colic lymph nodes were also infected in all macaques as either SIV DNA or infectious virus was recovered. Rapid SIV entry and dissemination is consistent with trans-epithelial transport. Virions appear to cross the follicle-associated epithelium, and also the digestive epithelium. Viral replication could however be more efficient in lymphoid aggregates. The initial sequence of events differs from both vaginal and oral infections, which implies that prevention strategies for rectal transmission will have to be specific. Microbicides will need to protect both digestive and follicle-associated epithelia. Vaccines will need to induce immunity in lymph nodes as well as in the rectum. PMID:21573012

Infection of Mouse Macrophages by Seasonal Influenza Viruses Can Be Restricted at the Level of Virus Entry and at a Late Stage in the Virus Life Cycle

PubMed Central

Londrigan, Sarah L.; Short, Kirsty R.; Ma, Joel; Gillespie, Leah; Rockman, Steven P.; Brooks, Andrew G.

2015-01-01

ABSTRACT Airway epithelial cells are susceptible to infection with seasonal influenza A viruses (IAV), resulting in productive virus replication and release. Macrophages (MΦ) are also permissive to IAV infection; however, virus replication is abortive. Currently, it is unclear how productive infection of MΦ is impaired or the extent to which seasonal IAV replicate in MΦ. Herein, we compared mouse MΦ and epithelial cells for their ability to support genomic replication and transcription, synthesis of viral proteins, assembly of virions, and release of infectious progeny following exposure to genetically defined IAV. We confirm that seasonal IAV differ in their ability to utilize cell surface receptors for infectious entry and that this represents one level of virus restriction. Following virus entry, we demonstrate synthesis of all eight segments of genomic viral RNA (vRNA) and mRNA, as well as seven distinct IAV proteins, in IAV-infected mouse MΦ. Although newly synthesized hemagglutinin (HA) and neuraminidase (NA) glycoproteins are incorporated into the plasma membrane and expressed at the cell surface, electron microscopy confirmed that virus assembly was defective in IAV-infected MΦ, defining a second level of restriction late in the virus life cycle. IMPORTANCE Seasonal influenza A viruses (IAV) and highly pathogenic avian influenza viruses (HPAI) infect macrophages, but only HPAI replicate productively in these cells. Herein, we demonstrate that impaired virus uptake into macrophages represents one level of restriction limiting infection by seasonal IAV. Following uptake, seasonal IAV do not complete productive replication in macrophages, representing a second level of restriction. Using murine macrophages, we demonstrate that productive infection is blocked late in the virus life cycle, such that virus assembly is defective and newly synthesized virions are not released. These studies represent an important step toward identifying host-encoded factors that block replication of seasonal IAV, but not HPAI, in macrophages. PMID:26423941

Infection of Mouse Macrophages by Seasonal Influenza Viruses Can Be Restricted at the Level of Virus Entry and at a Late Stage in the Virus Life Cycle.

PubMed

Londrigan, Sarah L; Short, Kirsty R; Ma, Joel; Gillespie, Leah; Rockman, Steven P; Brooks, Andrew G; Reading, Patrick C

2015-12-01

Airway epithelial cells are susceptible to infection with seasonal influenza A viruses (IAV), resulting in productive virus replication and release. Macrophages (MΦ) are also permissive to IAV infection; however, virus replication is abortive. Currently, it is unclear how productive infection of MΦ is impaired or the extent to which seasonal IAV replicate in MΦ. Herein, we compared mouse MΦ and epithelial cells for their ability to support genomic replication and transcription, synthesis of viral proteins, assembly of virions, and release of infectious progeny following exposure to genetically defined IAV. We confirm that seasonal IAV differ in their ability to utilize cell surface receptors for infectious entry and that this represents one level of virus restriction. Following virus entry, we demonstrate synthesis of all eight segments of genomic viral RNA (vRNA) and mRNA, as well as seven distinct IAV proteins, in IAV-infected mouse MΦ. Although newly synthesized hemagglutinin (HA) and neuraminidase (NA) glycoproteins are incorporated into the plasma membrane and expressed at the cell surface, electron microscopy confirmed that virus assembly was defective in IAV-infected MΦ, defining a second level of restriction late in the virus life cycle. Seasonal influenza A viruses (IAV) and highly pathogenic avian influenza viruses (HPAI) infect macrophages, but only HPAI replicate productively in these cells. Herein, we demonstrate that impaired virus uptake into macrophages represents one level of restriction limiting infection by seasonal IAV. Following uptake, seasonal IAV do not complete productive replication in macrophages, representing a second level of restriction. Using murine macrophages, we demonstrate that productive infection is blocked late in the virus life cycle, such that virus assembly is defective and newly synthesized virions are not released. These studies represent an important step toward identifying host-encoded factors that block replication of seasonal IAV, but not HPAI, in macrophages. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Topography of the Human Papillomavirus Minor Capsid Protein L2 during Vesicular Trafficking of Infectious Entry.

PubMed

DiGiuseppe, Stephen; Keiffer, Timothy R; Bienkowska-Haba, Malgorzata; Luszczek, Wioleta; Guion, Lucile G M; Müller, Martin; Sapp, Martin

2015-10-01

The human papillomavirus (HPV) capsid is composed of the major capsid protein L1 and the minor capsid protein L2. During entry, the HPV capsid undergoes numerous conformational changes that result in endosomal uptake and subsequent trafficking of the L2 protein in complex with the viral DNA to the trans-Golgi network. To facilitate this transport, the L2 protein harbors a number of putative motifs that, if capable of direct interaction, would interact with cytosolic host cell factors. These data imply that a portion of L2 becomes cytosolic during infection. Using a low concentration of digitonin to selectively permeabilize the plasma membrane of infected cells, we mapped the topography of the L2 protein during infection. We observed that epitopes within amino acid residues 64 to 81 and 163 to 170 and a C-terminal tag of HPV16 L2 are exposed on the cytosolic side of intracellular membranes, whereas an epitope within residues 20 to 38, which are upstream of a putative transmembrane region, is luminal. Corroborating these findings, we also found that L2 protein is sensitive to trypsin digestion during infection. These data demonstrate that the majority of the L2 protein becomes accessible on the cytosolic side of intracellular membranes in order to interact with cytosolic factors to facilitate vesicular trafficking. In order to complete infectious entry, nonenveloped viruses have to pass cellular membranes. This is often achieved through the viral capsid protein associating with or integrating into intracellular membrane. Here, we determine the topography of HPV L2 protein in the endocytic vesicular compartment, suggesting that L2 becomes a transmembrane protein with a short luminal portion and with the majority facing the cytosolic side for interaction with host cell transport factors. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Estimating the risk of communicable diseases aboard cargo ships.

PubMed

Schlaich, Clara C; Oldenburg, Marcus; Lamshöft, Maike M

2009-01-01

International travel and trade are known to be associated with the risk of spreading communicable diseases across borders. No international surveillance system for infectious diseases on ships exists. Outbreak reports and systematic studies mainly focus on disease activity on cruise ships. The study aims to assess the relevance of communicable disease occurrence on cargo ships. Retrospective analysis of all documented entries to 49 medical log books from seagoing cargo ships under German flag between 2000 and 2008. Incidence rates were calculated per 100 person-years at sea. Case series of acute respiratory illness, influenza-like illness, and infectious gastrointestinal illness affecting more than two persons within 1 successive week were classified as an outbreak. Attack rates were calculated based on number of entries to the medical log book in comparison to the average shipboard population during outbreak periods. During more than 1.5 million person-days of observation, 21% of the visits to the ship's infirmary were due to presumably communicable diseases (45.8 consultations per 100 person-years). As many as 33.9 patients per 100 person-years sought medical attention for acute respiratory symptoms. Of the 68 outbreaks that met predefined criteria, 66 were caused by acute respiratory illness with a subset of 12 outbreaks caused by influenza-like illness. Attack rates ranged between 3 and 10 affected seafarers per ship (12.5&-41.6% of the crew). Two outbreaks of gastrointestinal illness were detected. Respiratory illness is the most common cause of presumably communicable diseases aboard cargo ships and may cause outbreaks of considerable morbidity. Although the validity of the data is limited due to the use of nonprofessional diagnoses, missing or illegible entries, and restriction of the study population to German ships, the results provide guidance to ship owners and to Port Health Authorities to allocate resources and build capacities under International Health Regulations 2005.

Personal belief exemptions from school vaccination requirements.

PubMed

Diekema, Douglas S

2014-01-01

Despite the impact vaccination has had on the control and prevention of many infectious diseases, some parents choose not to vaccinate their children. Although there is no federal law requiring vaccination of children in the United States, all states require evidence of vaccination against at least some diseases as a condition of school entry. Which vaccines are required; how many doses are required; whether entry requirements apply to child care, kindergarten, or middle school; and whether exemptions from vaccine requirements will be allowed all differ by state. All but two states allow some kind of personal belief exemption from school vaccination requirements. This article reviews the history of school vaccination requirements and exemptions, the legal status of state vaccination laws and exemptions, the impact of school vaccination requirements and personal belief exemptions on vaccination rates and disease incidence, and strategies for maintaining adequate vaccination rates in states that allow personal belief exemptions.

Mimicking herpes simplex virus 1 and herpes simplex virus 2 mucosal behavior in a well-characterized human genital organ culture.

PubMed

Steukers, Lennert; Weyers, Steven; Yang, Xiaoyun; Vandekerckhove, Annelies P; Glorieux, Sarah; Cornelissen, Maria; Van den Broeck, Wim; Temmerman, Marleen; Nauwynck, Hans J

2014-07-15

We developed and morphologically characterized a human genital mucosa explant model (endocervix and ectocervix/vagina) to mimic genital herpes infections caused by herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Subsequent analysis of HSV entry receptor expression throughout the menstrual cycle in genital tissues was performed, and the evolution of HSV-1/-2 mucosal spread over time was assessed. Nectin-1 and -2 were expressed in all tissues during the entire menstrual cycle. Herpesvirus entry mediator expression was limited mainly to some connective tissue cells. Both HSV-1 and HSV-2 exhibited a plaque-wise mucosal spread across the basement membrane and induced prominent epithelial syncytia. © 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.

The nuclear retention signal of HPV16 L2 protein is essential for incoming viral genome to transverse the trans-Golgi network

PubMed Central

DiGiuseppe, Stephen; Bienkowska-Haba, Malgorzata; Hilbig, Lydia; Sapp, Martin

2014-01-01

The Human papillomavirus (HPV) capsid is composed of the major and minor capsid proteins, L1 and L2, respectively. Infectious entry requires a complex series of conformational changes in both proteins that lead to uptake and allow uncoating to occur. During entry, the capsid is disassembled and host cyclophilins dissociate L1 protein from the L2/DNA complex. Herein, we describe a mutant HPV16 L2 protein (HPV16 L2-R302/5A) that traffics pseudogenome to the trans-Golgi network (TGN) but fails to egress. Our data provide further evidence that HPV16 traffics through the TGN and demonstrates that L2 is essential for TGN egress. Furthermore, we show that cyclophilin activity is required for the L2/DNA complex to be transported to the TGN which is accompanied by a reduced L1 protein levels. PMID:24928042

Proteomics Tracing the Footsteps of Infectious Disease.

PubMed

Greco, Todd M; Cristea, Ileana M

2017-04-01

Every year, a major cause of human disease and death worldwide is infection with the various pathogens-viruses, bacteria, fungi, and protozoa-that are intrinsic to our ecosystem. In efforts to control the prevalence of infectious disease and develop improved therapies, the scientific community has focused on building a molecular picture of pathogen infection and spread. These studies have been aimed at defining the cellular mechanisms that allow pathogen entry into hosts cells, their replication and transmission, as well as the core mechanisms of host defense against pathogens. The past two decades have demonstrated the valuable implementation of proteomic methods in all these areas of infectious disease research. Here, we provide a perspective on the contributions of mass spectrometry and other proteomics approaches to understanding the molecular details of pathogen infection. Specifically, we highlight methods used for defining the composition of viral and bacterial pathogens and the dynamic interaction with their hosts in space and time. We discuss the promise of MS-based proteomics in supporting the development of diagnostics and therapies, and the growing need for multiomics strategies for gaining a systems view of pathogen infection. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Atypical pyoderma gangrenosum mimicking an infectious process.

PubMed

To, Derek; Wong, Aaron; Montessori, Valentina

2014-01-01

We present a patient with atypical pyoderma gangrenosum (APG), which involved the patient's arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics.

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

Luo, Sukun; University of Chinese Academy of Sciences, Beijing 100049; Hu, Kai

HSV-2 is the major cause of genital herpes and its infection increases the risk of HIV-1 acquisition and transmission. HSV-2 glycoprotein B together with glycoproteins D, H and L are indispensable for viral entry, of which gB, as a class III fusogen, plays an essential role. HSV-2 gB has seven potential N-linked glycosylation (N-CHO) sites, but their significance has yet to be determined. For the first time, we systematically analyzed the contributions of N-linked glycans on gB to cell–cell fusion and viral entry. Our results demonstrated that, of the seven potential N-CHO sites on gB, mutation at N390, N483 ormore » N668 decreased cell–cell fusion and viral entry, while mutation at N133 mainly affected protein expression and the production of infectious virus particles by blocking the transport of gB from the endoplasmic reticulum to Golgi. Our findings highlight the significance of N-linked glycans on HSV-2 gB expression and function. - Highlights: • N-linked glycan at N133 is important for gB intracellular trafficking and maturation. • N-linked glycans at N390, N483 and N668 on gB are necessary for optimal cell–cell fusion. • N-linked glycans at N390, N483 and N668 on gB are necessary for optimal viral entry.« less

Entry of Human Papillomavirus Type 16 by Actin-Dependent, Clathrin- and Lipid Raft-Independent Endocytosis

PubMed Central

Schelhaas, Mario; Shah, Bhavin; Holzer, Michael; Blattmann, Peter; Kühling, Lena; Day, Patricia M.; Schiller, John T.; Helenius, Ari

2012-01-01

Infectious endocytosis of incoming human papillomavirus type 16 (HPV-16), the main etiological agent of cervical cancer, is poorly characterized in terms of cellular requirements and pathways. Conflicting reports attribute HPV-16 entry to clathrin-dependent and -independent mechanisms. To comprehensively describe the cell biological features of HPV-16 entry into human epithelial cells, we compared HPV-16 pseudovirion (PsV) infection in the context of cell perturbations (drug inhibition, siRNA silencing, overexpression of dominant mutants) to five other viruses (influenza A virus, Semliki Forest virus, simian virus 40, vesicular stomatitis virus, and vaccinia virus) with defined endocytic requirements. Our analysis included infection data, i.e. GFP expression after plasmid delivery by HPV-16 PsV, and endocytosis assays in combination with electron, immunofluorescence, and video microscopy. The results indicated that HPV-16 entry into HeLa and HaCaT cells was clathrin-, caveolin-, cholesterol- and dynamin-independent. The virus made use of a potentially novel ligand-induced endocytic pathway related to macropinocytosis. This pathway was distinct from classical macropinocytosis in regards to vesicle size, cholesterol-sensitivity, and GTPase requirements, but similar in respect to the need for tyrosine kinase signaling, actin dynamics, Na+/H+ exchangers, PAK-1 and PKC. After internalization the virus was transported to late endosomes and/or endolysosomes, and activated through exposure to low pH. PMID:22536154

Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor.

PubMed

Cui, Qinghua; Du, Ruikun; Anantpadma, Manu; Schafer, Adam; Hou, Lin; Tian, Jingzhen; Davey, Robert A; Cheng, Han; Rong, Lijun

2018-03-27

The recent 2014-2016 West African Ebola virus epidemic underscores the need for the development of novel anti-Ebola therapeutics, due to the high mortality rates of Ebola virus infections and the lack of FDA-approved vaccine or therapy that is available for the prevention and treatment. Traditional Chinese medicines (TCMs) represent a huge reservoir of bioactive chemicals and many TCMs have been shown to have antiviral activities. 373 extracts from 128 TCMs were evaluated using a high throughput assay to screen for inhibitors of Ebola virus cell entry. Extract of Rhodiola rosea displayed specific and potent inhibition against cell entry of both Ebola virus and Marburg virus. In addition, twenty commercial compounds that were isolated from Rhodiola rosea were evaluated using the pseudotyped Ebola virus entry assay, and it was found that ellagic acid and gallic acid, which are two structurally related compounds, are the most effective ones. The activity of the extract and the two pure compounds were validated using infectious Ebola virus. The time-of-addition experiments suggest that, mechanistically, the Rhodiola rosea extract and the effective compounds act at an early step in the infection cycle following initial cell attachment, but prior to viral/cell membrane fusion. Our findings provide evidence that Rhodiola rosea has potent anti-filovirus properties that may be developed as a novel anti-Ebola treatment.

Establishment of pseudovirus infection mouse models for in vivo pharmacodynamics evaluation of filovirus entry inhibitors.

PubMed

Chen, Qing; Tang, Ke; Zhang, Xiaoyu; Chen, Panpan; Guo, Ying

2018-03-01

Filoviruses cause severe and fatal viral hemorrhagic fever in humans. Filovirus research has been extensive since the 2014 Ebola outbreak. Due to their high pathogenicity and mortality, live filoviruses require Biosafety Level-4 (BSL-4) facilities, which have restricted the development of anti-filovirus vaccines and drugs. An HIV-based pseudovirus cell infection assay is widely used for viral entry studies in BSL-2 conditions. Here, we successfully constructed nine in vitro pseudo-filovirus models covering all filovirus genera and three in vivo pseudo-filovirus-infection mouse models using Ebola virus, Marburg virus, and Lloviu virus as representative viruses. The pseudo-filovirus-infected mice showed visualizing bioluminescence in a dose-dependent manner. A bioluminescence peak in mice was reached on day 5 post-infection for Ebola virus and Marburg virus and on day 4 post-infection for Lloviu virus. Two known filovirus entry inhibitors, clomiphene and toremiphene, were used to validate the model. Collectively, our study shows that all genera of filoviruses can be well-pseudotyped and are infectious in vitro . The pseudo-filovirus-infection mouse models can be used for in vivo activity evaluation of anti-filovirus drugs. This sequential in vitro and in vivo evaluation system of filovirus entry inhibitors provides a secure and efficient platform for screening and assessing anti-filovirus agents in BSL-2 facilities.

Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor

PubMed Central

Cui, Qinghua; Du, Ruikun; Anantpadma, Manu; Schafer, Adam; Hou, Lin; Tian, Jingzhen; Cheng, Han; Rong, Lijun

2018-01-01

The recent 2014–2016 West African Ebola virus epidemic underscores the need for the development of novel anti-Ebola therapeutics, due to the high mortality rates of Ebola virus infections and the lack of FDA-approved vaccine or therapy that is available for the prevention and treatment. Traditional Chinese medicines (TCMs) represent a huge reservoir of bioactive chemicals and many TCMs have been shown to have antiviral activities. 373 extracts from 128 TCMs were evaluated using a high throughput assay to screen for inhibitors of Ebola virus cell entry. Extract of Rhodiola rosea displayed specific and potent inhibition against cell entry of both Ebola virus and Marburg virus. In addition, twenty commercial compounds that were isolated from Rhodiola rosea were evaluated using the pseudotyped Ebola virus entry assay, and it was found that ellagic acid and gallic acid, which are two structurally related compounds, are the most effective ones. The activity of the extract and the two pure compounds were validated using infectious Ebola virus. The time-of-addition experiments suggest that, mechanistically, the Rhodiola rosea extract and the effective compounds act at an early step in the infection cycle following initial cell attachment, but prior to viral/cell membrane fusion. Our findings provide evidence that Rhodiola rosea has potent anti-filovirus properties that may be developed as a novel anti-Ebola treatment. PMID:29584652

Simulation and experimental research on trans-media vehicle water-entry motion characteristics at low speed

PubMed Central

Yang, Jian; Feng, Jinfu; Hu, Junhua; Liu, An

2017-01-01

The motion characteristics of trans-media vehicles during the water-entry process were explored in this study in an effort to obtain the optimal water-entry condition of the vehicle for developing a novel, single control strategy integrating underwater non-control and in-air control. A water-entry dynamics model is established by combining the water-entry motion characteristics of the vehicle in uncontrolled conditions at low speed with time-varying parameters (e.g. buoyancy, added mass). A water-entry experiment is designed to confirm the effectiveness of the established model. After that, by comparing the experimental results with the simulated results, the model is further modified to more accurately reflect water-entry motion. The change laws of the vehicle’s attitude and position during the water-entry process are also obtained by analyzing the simulation of the modified model under different velocity, angle, and angle of attack conditions. The results presented here have guiding significance for the future realization of reaching the stable underwater navigation state of the vehicle after water-entry process. PMID:28558012

Simulation and experimental research on trans-media vehicle water-entry motion characteristics at low speed.

PubMed

Yang, Jian; Li, Yongli; Feng, Jinfu; Hu, Junhua; Liu, An

2017-01-01

The motion characteristics of trans-media vehicles during the water-entry process were explored in this study in an effort to obtain the optimal water-entry condition of the vehicle for developing a novel, single control strategy integrating underwater non-control and in-air control. A water-entry dynamics model is established by combining the water-entry motion characteristics of the vehicle in uncontrolled conditions at low speed with time-varying parameters (e.g. buoyancy, added mass). A water-entry experiment is designed to confirm the effectiveness of the established model. After that, by comparing the experimental results with the simulated results, the model is further modified to more accurately reflect water-entry motion. The change laws of the vehicle's attitude and position during the water-entry process are also obtained by analyzing the simulation of the modified model under different velocity, angle, and angle of attack conditions. The results presented here have guiding significance for the future realization of reaching the stable underwater navigation state of the vehicle after water-entry process.

A model-based tool to predict the propagation of infectious disease via airports.

PubMed

Hwang, Grace M; Mahoney, Paula J; James, John H; Lin, Gene C; Berro, Andre D; Keybl, Meredith A; Goedecke, D Michael; Mathieu, Jennifer J; Wilson, Todd

2012-01-01

Epidemics of novel or re-emerging infectious diseases have quickly spread globally via air travel, as highlighted by pandemic H1N1 influenza in 2009 (pH1N1). Federal, state, and local public health responders must be able to plan for and respond to these events at aviation points of entry. The emergence of a novel influenza virus and its spread to the United States were simulated for February 2009 from 55 international metropolitan areas using three basic reproduction numbers (R(0)): 1.53, 1.70, and 1.90. Empirical data from the pH1N1 virus were used to validate our SEIR model. Time to entry to the U.S. during the early stages of a prototypical novel communicable disease was predicted based on the aviation network patterns and the epidemiology of the disease. For example, approximately 96% of origins (R(0) of 1.53) propagated a disease into the U.S. in under 75 days, 90% of these origins propagated a disease in under 50 days. An R(0) of 1.53 reproduced the pH1NI observations. The ability to anticipate the rate and location of disease introduction into the U.S. provides greater opportunity to plan responses based on the scenario as it is unfolding. This simulation tool can aid public health officials to assess risk and leverage resources efficiently. Copyright © 2012 Elsevier Ltd. All rights reserved.

Several Human Liver Cell Expressed Apolipoproteins Complement HCV Virus Production with Varying Efficacy Conferring Differential Specific Infectivity to Released Viruses.

PubMed

Hueging, Kathrin; Weller, Romy; Doepke, Mandy; Vieyres, Gabrielle; Todt, Daniel; Wölk, Benno; Vondran, Florian W R; Geffers, Robert; Lauber, Chris; Kaderali, Lars; Penin, François; Pietschmann, Thomas

2015-01-01

Apolipoprotein E (ApoE), an exchangeable apolipoprotein, is necessary for production of infectious Hepatitis C virus (HCV) particles. However, ApoE is not the only liver-expressed apolipoprotein and the role of other apolipoproteins for production of infectious HCV progeny is incompletely defined. Therefore, we quantified mRNA expression of human apolipoproteins in primary human hepatocytes. Subsequently, cDNAs encoding apolipoproteins were expressed in 293T/miR-122 cells to explore if they complement HCV virus production in cells that are non-permissive due to limiting endogenous levels of human apolipoproteins. Primary human hepatocytes expressed high mRNA levels of ApoA1, A2, C1, C3, E, and H. ApoA4, A5, B, D, F, J, L1, L2, L3, L4, L6, M, and O were expressed at intermediate levels, and C2, C4, and L5 were not detected. All members of the ApoA and ApoC family of lipoproteins complemented HCV virus production in HCV transfected 293T/miR-122 cells, albeit with significantly lower efficacy compared with ApoE. In contrast, ApoD expression did not support production of infectious HCV. Specific infectivity of released particles complemented with ApoA family members was significantly lower compared with ApoE. Moreover, the ratio of extracellular to intracellular infectious virus was significantly higher for ApoE compared to ApoA2 and ApoC3. Since apolipoproteins complementing HCV virus production share amphipathic alpha helices as common structural features we altered the two alpha helices of ApoC1. Helix breaking mutations in both ApoC1 helices impaired virus assembly highlighting a critical role of alpha helices in apolipoproteins supporting HCV assembly. In summary, various liver expressed apolipoproteins with amphipathic alpha helices complement HCV virus production in human non liver cells. Differences in the efficiency of virus assembly, the specific infectivity of released particles, and the ratio between extracellular and intracellular infectivity point to distinct characteristics of these apolipoproteins that influence HCV assembly and cell entry. This will guide future research to precisely pinpoint how apolipoproteins function during virus assembly and cell entry.

Several Human Liver Cell Expressed Apolipoproteins Complement HCV Virus Production with Varying Efficacy Conferring Differential Specific Infectivity to Released Viruses

PubMed Central

Doepke, Mandy; Vieyres, Gabrielle; Todt, Daniel; Wölk, Benno; Vondran, Florian W. R.; Geffers, Robert; Lauber, Chris; Kaderali, Lars; Penin, François; Pietschmann, Thomas

2015-01-01

Apolipoprotein E (ApoE), an exchangeable apolipoprotein, is necessary for production of infectious Hepatitis C virus (HCV) particles. However, ApoE is not the only liver-expressed apolipoprotein and the role of other apolipoproteins for production of infectious HCV progeny is incompletely defined. Therefore, we quantified mRNA expression of human apolipoproteins in primary human hepatocytes. Subsequently, cDNAs encoding apolipoproteins were expressed in 293T/miR-122 cells to explore if they complement HCV virus production in cells that are non-permissive due to limiting endogenous levels of human apolipoproteins. Primary human hepatocytes expressed high mRNA levels of ApoA1, A2, C1, C3, E, and H. ApoA4, A5, B, D, F, J, L1, L2, L3, L4, L6, M, and O were expressed at intermediate levels, and C2, C4, and L5 were not detected. All members of the ApoA and ApoC family of lipoproteins complemented HCV virus production in HCV transfected 293T/miR-122 cells, albeit with significantly lower efficacy compared with ApoE. In contrast, ApoD expression did not support production of infectious HCV. Specific infectivity of released particles complemented with ApoA family members was significantly lower compared with ApoE. Moreover, the ratio of extracellular to intracellular infectious virus was significantly higher for ApoE compared to ApoA2 and ApoC3. Since apolipoproteins complementing HCV virus production share amphipathic alpha helices as common structural features we altered the two alpha helices of ApoC1. Helix breaking mutations in both ApoC1 helices impaired virus assembly highlighting a critical role of alpha helices in apolipoproteins supporting HCV assembly. In summary, various liver expressed apolipoproteins with amphipathic alpha helices complement HCV virus production in human non liver cells. Differences in the efficiency of virus assembly, the specific infectivity of released particles, and the ratio between extracellular and intracellular infectivity point to distinct characteristics of these apolipoproteins that influence HCV assembly and cell entry. This will guide future research to precisely pinpoint how apolipoproteins function during virus assembly and cell entry. PMID:26226615

[Current aspects of the physiopathology of the infectious process. II. Cybernetic elements in the pathogenetic structure of infectious diseases].

PubMed

Dragomirescu, M; Buzinschi, S

1980-01-01

The authors discuss the applicability of general cybernetic principles (the theory of systems and self-regulated mechanisms based on inversed connections) to the pathophysiologic structure of infections. With reference to concrete examples they outline the following elements: the appartenance of the infectious process to the notion of system (as conceived in the theory of systems), the previsible character of the functional potential of the structured system in the components of infection, and the sequental correspondence between system dynamics and the dynamics of the infectious process. Starting from the mechanism of action of the main microbial toxins, the aptitude of the latter to act upon the functional code of the macroorganism, altering the cellular and supracellular self-regulated biosystems, is demonstrated. Finally, the practical implications of assimilating cybernetic processes in the pathophysiology of infectious diseases are analyzed.

19 CFR 143.35 - Procedure for electronic entry summary.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 2 2012-04-01 2012-04-01 false Procedure for electronic entry summary. 143.35...; DEPARTMENT OF THE TREASURY (CONTINUED) SPECIAL ENTRY PROCEDURES Electronic Entry Filing § 143.35 Procedure for electronic entry summary. In order to obtain entry summary processing electronically, the filer...

19 CFR 143.35 - Procedure for electronic entry summary.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 2 2011-04-01 2011-04-01 false Procedure for electronic entry summary. 143.35...; DEPARTMENT OF THE TREASURY (CONTINUED) SPECIAL ENTRY PROCEDURES Electronic Entry Filing § 143.35 Procedure for electronic entry summary. In order to obtain entry summary processing electronically, the filer...

19 CFR 143.35 - Procedure for electronic entry summary.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Procedure for electronic entry summary. 143.35...; DEPARTMENT OF THE TREASURY (CONTINUED) SPECIAL ENTRY PROCEDURES Electronic Entry Filing § 143.35 Procedure for electronic entry summary. In order to obtain entry summary processing electronically, the filer...

The Macrophage Galactose-Type Lectin Can Function as an Attachment and Entry Receptor for Influenza Virus

PubMed Central

Ng, Wy Ching; Liong, Stella; Tate, Michelle D.; Irimura, Tatsuro; Denda-Nagai, Kaori; Brooks, Andrew G.; Londrigan, Sarah L.

2014-01-01

Specific protein receptors that mediate internalization and entry of influenza A virus (IAV) have not been identified for any cell type. Sialic acid (SIA), the primary attachment factor for IAV hemagglutinin, is expressed by numerous cell surface glycoproteins and glycolipids, confounding efforts to identify specific receptors involved in virus infection. Lec1 Chinese hamster ovary (CHO) epithelial cells express cell surface SIA and bind IAV yet are largely resistant to infection. Here, we demonstrate that expression of the murine macrophage galactose-type lectin 1 (MGL1) by Lec1 cells enhanced Ca2+-dependent IAV binding and restored permissivity to infection. Lec1 cells expressing MGL1 were infected in the presence or absence of cell surface SIA, indicating that MGL1 can act as a primary receptor or as a coreceptor with SIA. Lec1 cells expressing endocytosis-deficient MGL1 mediated Ca2+-dependent IAV binding but were less sensitive to IAV infection, indicating that direct internalization via MGL1 can result in cellular infection. Together, these studies identify MGL1 as a cell surface glycoprotein that can act as an authentic receptor for both attachment and infectious entry of IAV. PMID:24257596

Atypical Pyoderma Gangrenosum Mimicking an Infectious Process

PubMed Central

To, Derek; Wong, Aaron; Montessori, Valentina

2014-01-01

We present a patient with atypical pyoderma gangrenosum (APG), which involved the patient's arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics. PMID:25024856

19 CFR 142.11 - Entry summary form.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry summary form. 142.11 Section 142.11 Customs... (CONTINUED) ENTRY PROCESS Entry Summary Documentation § 142.11 Entry summary form. (a) Customs Form 7501. The entry summary shall be on Customs Form 7501 unless a different form is prescribed elsewhere in this...

Antiviral mechanism of polyanionic carbosilane dendrimers against HIV-1

PubMed Central

Vacas-Córdoba, Enrique; Maly, Marek; De la Mata, Francisco J; Gómez, Rafael; Pion, Marjorie; Muñoz-Fernández, Mª Ángeles

2016-01-01

Nanotechnology-derived platforms, such as dendrimers, are very attractive in several biological applications. In the case of human immunodeficiency virus (HIV) infection, polyanionic carbosilane dendrimers have shown great potential as antiviral agents in the development of novel microbicides to prevent the sexual transmission of HIV-1. In this work, we studied the mechanism of two sulfated and naphthylsulfonated functionalized carbosilane dendrimers, G3-S16 and G2-NF16. They are able to inhibit viral infection at fusion and thus at the entry step. Both compounds impede the binding of viral particles to target cell surface and membrane fusion through the blockage of gp120–CD4 interaction. In addition, and for the first time, we demonstrate that dendrimers can inhibit cell-to-cell HIV transmission and difficult infectious synapse formation. Thus, carbosilane dendrimers’ mode of action is a multifactorial process targeting several proteins from viral envelope and from host cells that could block HIV infection at different stages during the first step of infection. PMID:27103798

Betel quid use in relation to infectious disease outcomes in Cambodia

PubMed Central

Singh, Pramil N.; Natto, Zuhair; Yel, Daravuth; Job, Jayakaran; Knutsen, Synnove

2012-01-01

Summary Objectives The habitual chewing of betel quid (areca nut, betel leaf, tobacco) is estimated to occur among 600 million persons in Asia and the Asia-Pacific Region. Emerging data from rural Asia indicate that the betel quid is part of traditional medicine practices that promote its use for a wide range of ailments, including infectious disease. In the present study, we examined the association between betel quid, traditional medicine, and infectious disease outcomes. Methods For the purpose of a nationwide, interviewer-administered, cross-sectional survey of tobacco use (including betel quid), we conducted a stratified three-stage cluster sampling of 13 988 adults aged 18 years and older from all provinces of Cambodia. Results We found an association between the intensity of betel quid use and HIV/AIDS (odds ratio (OR) 2.06, 95% CI 1.09–3.89), dengue fever (OR 2.40, 95% CI 1.55–2.72), tuberculosis (OR 1.50, 95% CI 0.96–2.36), and typhoid (OR 1.48, 95% CI 0.95–2.30). These associations were even stronger in women – the primary users of betel quid in Cambodia. Multivariable analyses that controlled for age, gender, income, education, urban versus rural dwelling, receiving care from traditional medicine practitioners, and cigarette smoking did not alter the betel quid–infectious disease association. Conclusions Our findings raise the possibility of a role of betel quid use in the transmission of infectious disease through pathways such as immunosuppression, oral route of entry for a pathogen (i.e., through injury to the oral mucosa), and contamination (i.e., fecal–oral) of the betel quid ingredients. PMID:22296863

Carbon nanotubes as vaccine scaffolds

PubMed Central

Scheinberg, David A.; McDevitt, Michael R.; Dao, Tao; Mulvey, Justin J.; Feinberg, Evan; Alidori, Simone

2013-01-01

Carbon nanotubes display characteristics that are potentially useful in their development as scaffolds for vaccine compositions. These features include stability in vivo, lack of intrinsic immunogenicity, low toxicity, and the ability to be appended with multiple copies of antigens. In addition, the particulate nature of carbon nanotubes and their unusual properties of rapid entry into antigen-presenting cells, such as dendritic cells, make them especially useful as carriers of antigens. Early attempts demonstrating carbon nanotube-based vaccines can be used in both infectious disease settings and cancer are promising. PMID:23899863

Creative PDB`s (parts databases)

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

Cote, T.J.

1998-12-31

PDB component property entries and creative picklists can make the schematic entry process and downstream tools such as BOM generation more useful. This presentation will show how creative PDB`s can enhance the design process. Examples of PDB entries developed at Los Alamos National Laboratory will be discussed.

Childhood developmental vulnerabilities associated with early life exposure to infectious and noninfectious diseases and maternal mental illness.

PubMed

Green, Melissa J; Kariuki, Maina; Dean, Kimberlie; Laurens, Kristin R; Tzoumakis, Stacy; Harris, Felicity; Carr, Vaughan J

2017-12-26

Fetal exposure to infectious and noninfectious diseases may influence early childhood developmental functioning, on the path to later mental illness. Here, we investigated the effects of in utero exposure to maternal infection and noninfectious diseases during pregnancy on offspring developmental vulnerabilities at age 5 years, in the context of estimated effects for early childhood exposures to infectious and noninfectious diseases and maternal mental illness. We used population data for 66,045 children from an intergenerational record linkage study (the New South Wales Child Development Study), for whom a cross-sectional assessment of five developmental competencies (physical, social, emotional, cognitive, and communication) was obtained at school entry, using the Australian Early Development Census (AEDC). Child and maternal exposures to infectious or noninfectious diseases were determined from the NSW Ministry of Health Admitted Patients Data Collection (APDC) and maternal mental illness exposure was derived from both APDC and Mental Health Ambulatory Data collections. Multinomial logistic regression analyses were used to examine unadjusted and adjusted associations between these physical and mental health exposures and child developmental vulnerabilities at age 5 years. Among the physical disease exposures, maternal infectious diseases during pregnancy and early childhood infection conferred the largest associations with developmental vulnerabilities at age 5 years; maternal noninfectious illness during pregnancy also retained small but significant associations with developmental vulnerabilities even when adjusted for other physical and mental illness exposures and covariates known to be associated with early childhood development (e.g., child's sex, socioeconomic disadvantage, young maternal age, prenatal smoking). Among all exposures examined, maternal mental illness first diagnosed prior to childbirth conferred the greatest odds of developmental vulnerability at age 5 years. Prenatal exposure to infectious or noninfectious diseases appear to influence early childhood physical, social, emotional and cognitive developmental vulnerabilities that may represent intermediate phenotypes for subsequent mental disorders. © 2017 Association for Child and Adolescent Mental Health.

Distinct seasonal infectious agent profiles in life-history variants of juvenile Fraser River Chinook salmon: An application of high-throughput genomic screening.

PubMed

Tucker, Strahan; Li, Shaorong; Kaukinen, Karia H; Patterson, David A; Miller, Kristina M

2018-01-01

Disease-causing infectious agents are natural components of ecosystems and considered a major selective force driving the evolution of host species. However, knowledge of the presence and abundance of suites of infectious agents in wild populations has been constrained by our ability to easily screen for them. Using salmon as a model, we contrasted seasonal pathogenic infectious agents in life history variants of juvenile Chinook salmon from the Fraser River system (N = 655), British Columbia (BC), through the application of a novel high-throughput quantitative PCR monitoring platform. This included freshwater hatchery origin fish and samples taken at sea between ocean entry in spring and over-winter residence in coastal waters. These variants currently display opposite trends in productivity, with yearling stocks generally in decline and sub-yearling stocks doing comparatively well. We detected the presence of 32 agents, 21 of which were at >1% prevalence. Variants carried a different infectious agent profile in terms of (1) diversity, (2) origin or transmission environment of infectious agents, and (3) prevalence and abundance of individual agents. Differences in profiles tended to reflect differential timing and residence patterns through freshwater, estuarine and marine habitats. Over all seasons, individual salmon carried an average of 3.7 agents. Diversity changed significantly, increasing upon saltwater entrance, increasing through the fall and decreasing slightly in winter. Diversity varied between life history types with yearling individuals carrying 1.3-times more agents on average. Shifts in prevalence and load over time were examined to identify agents with the greatest potential for impact at the stock level; those displaying concurrent decrease in prevalence and load truncation with time. Of those six that had similar patterns in both variants, five reached higher prevalence in yearling fish while only one reached higher prevalence in sub-yearling fish; this pattern was present for an additional five agents in yearling fish only.

Distinct seasonal infectious agent profiles in life-history variants of juvenile Fraser River Chinook salmon: An application of high-throughput genomic screening

PubMed Central

Li, Shaorong; Kaukinen, Karia H.; Patterson, David A.; Miller, Kristina M.

2018-01-01

Disease-causing infectious agents are natural components of ecosystems and considered a major selective force driving the evolution of host species. However, knowledge of the presence and abundance of suites of infectious agents in wild populations has been constrained by our ability to easily screen for them. Using salmon as a model, we contrasted seasonal pathogenic infectious agents in life history variants of juvenile Chinook salmon from the Fraser River system (N = 655), British Columbia (BC), through the application of a novel high-throughput quantitative PCR monitoring platform. This included freshwater hatchery origin fish and samples taken at sea between ocean entry in spring and over-winter residence in coastal waters. These variants currently display opposite trends in productivity, with yearling stocks generally in decline and sub-yearling stocks doing comparatively well. We detected the presence of 32 agents, 21 of which were at >1% prevalence. Variants carried a different infectious agent profile in terms of (1) diversity, (2) origin or transmission environment of infectious agents, and (3) prevalence and abundance of individual agents. Differences in profiles tended to reflect differential timing and residence patterns through freshwater, estuarine and marine habitats. Over all seasons, individual salmon carried an average of 3.7 agents. Diversity changed significantly, increasing upon saltwater entrance, increasing through the fall and decreasing slightly in winter. Diversity varied between life history types with yearling individuals carrying 1.3-times more agents on average. Shifts in prevalence and load over time were examined to identify agents with the greatest potential for impact at the stock level; those displaying concurrent decrease in prevalence and load truncation with time. Of those six that had similar patterns in both variants, five reached higher prevalence in yearling fish while only one reached higher prevalence in sub-yearling fish; this pattern was present for an additional five agents in yearling fish only. PMID:29672620

A Library of Infectious Hepatitis C Viruses with Engineered Mutations in the E2 Gene Reveals Growth-Adaptive Mutations That Modulate Interactions with Scavenger Receptor Class B Type I.

PubMed

Zuiani, Adam; Chen, Kevin; Schwarz, Megan C; White, James P; Luca, Vincent C; Fremont, Daved H; Wang, David; Evans, Matthew J; Diamond, Michael S

2016-12-01

While natural hepatitis C virus (HCV) infection results in highly diverse quasispecies of related viruses over time, mutations accumulate more slowly in tissue culture, in part because of the inefficiency of replication in cells. To create a highly diverse population of HCV particles in cell culture and identify novel growth-enhancing mutations, we engineered a library of infectious HCV with all codons represented at most positions in the ectodomain of the E2 gene. We identified many putative growth-adaptive mutations and selected nine highly represented E2 mutants for further study: Q412R, T416R, S449P, T563V, A579R, L619T, V626S, K632T, and L644I. We evaluated these mutants for changes in particle-to-infectious-unit ratio, sensitivity to neutralizing antibody or CD81 large extracellular loop (CD81-LEL) inhibition, entry factor usage, and buoyant density profiles. Q412R, T416R, S449P, T563V, and L619T were neutralized more efficiently by anti-E2 antibodies and T416R, T563V, and L619T by CD81-LEL. Remarkably, all nine variants showed reduced dependence on scavenger receptor class B type I (SR-BI) for infection. This shift from SR-BI usage did not correlate with a change in the buoyant density profiles of the variants, suggesting an altered E2-SR-BI interaction rather than changes in the virus-associated lipoprotein-E2 interaction. Our results demonstrate that residues influencing SR-BI usage are distributed across E2 and support the development of large-scale mutagenesis studies to identify viral variants with unique functional properties. Characterizing variant viruses can reveal new information about the life cycle of HCV and the roles played by different viral genes. However, it is difficult to recapitulate high levels of diversity in the laboratory because of limitations in the HCV culture system. To overcome this limitation, we engineered a library of mutations into the E2 gene in the context of an infectious clone of the virus. We used this library of viruses to identify nine mutations that enhance the growth rate of HCV. These growth-enhancing mutations reduced the dependence on a key entry receptor, SR-BI. By generating a highly diverse library of infectious HCV, we mapped regions of the E2 protein that influence a key virus-host interaction and provide proof of principle for the generation of large-scale mutant libraries for the study of pathogens with great sequence variability. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Cytopathological process by multiple nucleopolyhedrovirus in the testis of Bombyx mori L., 1758 (Lepidoptera: Bombycidae).

PubMed

Pereira, Eliana Peliçon; Conte, Hélio; Ribeiro, Lucinéia de Fátima Chasko; Zanatta, Daniela Bertolini; Bravo, Juliana Pereira; Fernandez, Maria Aparecida; Brancalhão, Rose Meire Costa

2008-09-01

A cytopathological methodology was used to analyze infection by Bombyx mori multiple nucleopolyhedrovirus (BmMNPV), a geographic isolate of the family Baculoviridae, in the caterpillar testes of the B. mori. Japanese B. mori strain caterpillar, fifth instar, were inoculated with BmMNPV and their testes were collected and processed for light and transmission electronic microscopy. Epithelial coating cells and interfollicular septa in testes were susceptible to BmMNPV. The first evidence of infection was detected on the 6th day post-inoculation (p.i.) in the external epithelium, and on the 7th day p.i. in the internal epithelium and interfollicular septa. Cytopathological characteristics consisted of hypertrophied nuclei, the formation of virogenic stroma, and the occlusion of virions in polyhedron protein crystals in several stages of development. At the end of the infectious process, cell lysis and release of polyhedra into the extracellular medium occurred. Histopathology revealed early infection foci in the surrounding regions of tracheal insertions, thus underlining the role of the trachea as an infection-spreading organ in insects. This spreading occurs through penetration of the basal lamina, which facilitates entry of the budded virus into the testis. Additionally, an alignment of a partial sequence of the ORF 14 of the BmMNPV geographic isolate with other NPV certified the virus genera.

Adventures in Parallel Processing: Entry, Descent and Landing Simulation for the Genesis and Stardust Missions

NASA Technical Reports Server (NTRS)

Lyons, Daniel T.; Desai, Prasun N.

2005-01-01

This paper will describe the Entry, Descent and Landing simulation tradeoffs and techniques that were used to provide the Monte Carlo data required to approve entry during a critical period just before entry of the Genesis Sample Return Capsule. The same techniques will be used again when Stardust returns on January 15, 2006. Only one hour was available for the simulation which propagated 2000 dispersed entry states to the ground. Creative simulation tradeoffs combined with parallel processing were needed to provide the landing footprint statistics that were an essential part of the Go/NoGo decision that authorized release of the Sample Return Capsule a few hours before entry.

A push-pull system to reduce house entry of malaria mosquitoes

PubMed Central

2014-01-01

Background Mosquitoes are the dominant vectors of pathogens that cause infectious diseases such as malaria, dengue, yellow fever and filariasis. Current vector control strategies often rely on the use of pyrethroids against which mosquitoes are increasingly developing resistance. Here, a push-pull system is presented, that operates by the simultaneous use of repellent and attractive volatile odorants. Method/Results Experiments were carried out in a semi-field set-up: a traditional house which was constructed inside a screenhouse. The release of different repellent compounds, para-menthane-3,8-diol (PMD), catnip oil e.o. and delta-undecalactone, from the four corners of the house resulted in significant reductions of 45% to 81.5% in house entry of host-seeking malaria mosquitoes. The highest reductions in house entry (up to 95.5%), were achieved by simultaneously repelling mosquitoes from the house (push) and removing them from the experimental set-up using attractant-baited traps (pull). Conclusions The outcome of this study suggests that a push-pull system based on attractive and repellent volatiles may successfully be employed to target mosquito vectors of human disease. Reductions in house entry of malaria vectors, of the magnitude that was achieved in these experiments, would likely affect malaria transmission. The repellents used are non-toxic and can be used safely in a human environment. Delta-undecalactone is a novel repellent that showed higher effectiveness than the established repellent PMD. These results encourage further development of the system for practical implementation in the field. PMID:24674451

Intracellular modifications induced by poliovirus reduce the requirement for structural motifs in the 5' noncoding region of the genome involved in internal initiation of protein synthesis.

PubMed Central

Percy, N; Belsham, G J; Brangwyn, J K; Sullivan, M; Stone, D M; Almond, J W

1992-01-01

A series of genetic deletions based partly on two RNA secondary structure models (M. A. Skinner, V. R. Racaniello, G. Dunn, J. Cooper, P. D. Minor, and J. W. Almond, J. Mol. Biol. 207:379-392, 1989; E. V. Pilipenko, V. M. Blinov, L. I. Romanova, A. N. Sinyakov, S. V. Maslova, and V. I. Agol, Virology 168:201-209, 1989) was made in the cDNA encoding the 5' noncoding region (5' NCR) of the poliovirus genome in order to study the sequences that direct the internal entry of ribosomes. The modified cDNAs were placed between two open reading frames in a single transcriptional unit and used to transfect cells in culture. Internal entry of ribosomes was detected by measuring translation from the second open reading frame in the bicistronic mRNA. When assayed alone, a large proportion of the poliovirus 5' NCR superstructure including several well-defined stem-loops was required for ribosome entry and efficient translation. However, in cells cotransfected with a complete infectious poliovirus cDNA, the requirement for the stem-loops in this large superstructure was reduced. The results suggest that virus infection modifies the cellular translational machinery, so that shortened forms of the 5' NCR are sufficient for cap-independent translation, and that the internal entry of ribosomes occurs by two distinct modes during the virus replication cycle. Images PMID:1310772

The Role of Conserved N-Linked Glycans on Ebola Virus Glycoprotein 2.

PubMed

Lennemann, Nicholas J; Walkner, Madeline; Berkebile, Abigail R; Patel, Neil; Maury, Wendy

2015-10-01

N-linked glycosylation is a common posttranslational modification found on viral glycoproteins (GPs) and involved in promoting expression, cellular attachment, protection from proteases, and antibody evasion. The GP subunit GP2 of filoviruses contains 2 completely conserved N-linked glycosylation sites (NGSs) at N563 and N618, suggesting that they have been maintained through selective pressures. We assessed mutants lacking these glycans for expression and function to understand the role of these sites during Ebola virus entry. Elimination of either GP2 glycan individually had a modest effect on GP expression and no impact on antibody neutralization of vesicular stomatitis virus pseudotyped with Ebola virus GP. However, loss of the N563 glycan enhanced entry by 2-fold and eliminated GP detection by a well-characterized monoclonal antibody KZ52. Loss of both sites dramatically decreased GP expression and abolished entry. Surprisingly, a GP that retained a single NGS at N563, eliminating the remaining 16 NGSs from GP1 and GP2, had detectable expression, a modest increase in entry, and pronounced sensitivity to antibody neutralization. Our findings support the importance of the GP2 glycans in GP expression/structure, transduction efficiency, and antibody neutralization, particularly when N-linked glycans are also removed from GP1. © The Author 2015. 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.

Molecular determinants of dengue virus 2 envelope protein important for virus entry in FcγRIIA-mediated antibody-dependent enhancement of infection

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

Chotiwan, Nunya; Roehrig, John T.; Schlesinger, Jacob J.

Antibody-dependent enhancement (ADE) of infection may cause severe illness in patients suffering a secondary infection by a heterologous dengue virus (DENV) serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing antibodies form infectious virus-Ab complexes with the newly infecting serotype and enhance virus infection by binding to the Fcγ receptors (FcγR) on FcγR-bearing cells. In this study, we determined that molecular determinants of DENV2 envelope protein critical for virus entry during non-ADE infection are also required for ADE infection mediated by FcγRIIA, and binding of virus-Ab complexes with FcγRIIA alone is not sufficient for ADE of infection. The FcγRIIA mainlymore » plays an auxiliary role in concentrating the virus–Ab complex to the cell surface, and other primary cellular receptors are required for virus entry. Understanding the viral entry pathway in ADE of DENV infection will greatly facilitate rational designs of anti-viral therapeutics against severe dengue disease associated with ADE. - Highlights: • KKK305/307/310 in DENV2 E-DIII is critical for virus attachment in ADE and non-ADE infection. • Binding of DENV2–Ab complex with FcγRII alone is not sufficient for virus entry in ADE infection. • Other primary receptors were required for DENV2 internalization during FcγRII–mediated ADE. • G104 and L135 of DENV2 E are critical for virus-mediated membrane fusion. • DENV2 virus-mediated membrane fusion is required for both ADE and non-ADE infection.« less

The spread of zoonoses and other infectious diseases through the international trade of animals and animal products.

PubMed

Seimenis, Aristarhos M

2008-01-01

For trade purposes, ever increasing quantities of food animals and animal products that are transported more rapidly than ever before are contributing to the spread of zoonoses and are creating threats on a permanent basis. Most countries in south-eastern Europe, the Mediterranean and the Middle East are increasing imports of food animals and meat and products of animal origin. They can become potential sources of zoonotic and other infectious diseases if controls are not performed under the most effective conditions. Developing countries with their organisational weakness are particularly vulnerable to fraudulent international trade practices of animals and animal products. To prevent such risks, the World Trade Organization, the World Organisation for Animal Health and their member countries support the measures stipulated in the Sanitary and Phytosanitary Agreement which targets the liberalisation of trade in animals and animal products under specific conditions while protecting public health and national economies. Vigilance must be exercised and appropriate inspection made at points of entry by veterinary and other authorities to ensure the strict implementation of international and national regulations. National legislation, appropriate infrastructures and the respect of international regulations can become barriers to avoid animal trade, contributing to the spread of zoonotic and other infectious diseases.

Does attention speed up processing? Decreases and increases of processing rates in visual prior entry.

PubMed

Tünnermann, Jan; Petersen, Anders; Scharlau, Ingrid

2015-03-02

Selective visual attention improves performance in many tasks. Among others, it leads to "prior entry"--earlier perception of an attended compared to an unattended stimulus. Whether this phenomenon is purely based on an increase of the processing rate of the attended stimulus or if a decrease in the processing rate of the unattended stimulus also contributes to the effect is, up to now, unanswered. Here we describe a novel approach to this question based on Bundesen's Theory of Visual Attention, which we use to overcome the limitations of earlier prior-entry assessment with temporal order judgments (TOJs) that only allow relative statements regarding the processing speed of attended and unattended stimuli. Prevalent models of prior entry in TOJs either indirectly predict a pure acceleration or cannot model the difference between acceleration and deceleration. In a paradigm that combines a letter-identification task with TOJs, we show that indeed acceleration of the attended and deceleration of the unattended stimuli conjointly cause prior entry. © 2015 ARVO.

19 CFR 142.44 - Entry number range.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 2 2013-04-01 2013-04-01 false Entry number range. 142.44 Section 142.44 Customs... (CONTINUED) ENTRY PROCESS Line Release § 142.44 Entry number range. After an application for Line Release has received final approval, filers must provide the port director, in writing, with a range of entry numbers...

A Single Amino Acid Substitution in the Core Protein of West Nile Virus Increases Resistance to Acidotropic Compounds

PubMed Central

Martín-Acebes, Miguel A.; Blázquez, Ana-Belén; de Oya, Nereida Jiménez; Escribano-Romero, Estela; Shi, Pei-Yong; Saiz, Juan-Carlos

2013-01-01

West Nile virus (WNV) is a worldwide distributed mosquito-borne flavivirus that naturally cycles between birds and mosquitoes, although it can infect multiple vertebrate hosts including horses and humans. This virus is responsible for recurrent epidemics of febrile illness and encephalitis, and has recently become a global concern. WNV requires to transit through intracellular acidic compartments at two different steps to complete its infectious cycle. These include fusion between the viral envelope and the membrane of endosomes during viral entry, and virus maturation in the trans-Golgi network. In this study, we followed a genetic approach to study the connections between viral components and acidic pH. A WNV mutant with increased resistance to the acidotropic compound NH4Cl, which blocks organelle acidification and inhibits WNV infection, was selected. Nucleotide sequencing revealed that this mutant displayed a single amino acid substitution (Lys 3 to Glu) on the highly basic internal capsid or core (C) protein. The functional role of this replacement was confirmed by its introduction into a WNV infectious clone. This single amino acid substitution also increased resistance to other acidification inhibitor (concanamycin A) and induced a reduction of the neurovirulence in mice. Interestingly, a naturally occurring accompanying mutation found on prM protein abolished the resistant phenotype, supporting the idea of a genetic crosstalk between the internal C protein and the external glycoproteins of the virion. The findings here reported unveil a non-previously assessed connection between the C viral protein and the acidic pH necessary for entry and proper exit of flaviviruses. PMID:23874963

Study of RNA-A Initiation Translation of The Infectious Pancreatic Necrosis Virus.

PubMed

Rivas-Aravena, Andrea; Muñoz, Patricio; Jorquera, Patricia; Diaz, Alvaro; Reinoso, Claudia; González-Catrilelbún, Sebastián; Sandino, Ana María

2017-08-15

The infectious pancreatic necrosis virus (IPNV) is a salmonid pathogen that causes significant economic losses to the aquaculture industry. IPNV is a non-enveloped virus containing two uncapped and non-polyadenylated double strand RNA genomic segments, RNA-A and RNA-B. The viral protein Vpg is covalently attached to the 5' end of both segments. There is little knowledge about its viral cycle, particularly about the translation of the RNAs. Through experiments using mono and bicistronic reporters, in this work we show that the 120-nucleotide-long 5'-UTR of RNA-A contains an internal ribosome entry site (IRES) that functions efficiently both in vitro and in salmon cells. IRES activity is strongly dependent on temperature. Also, the IRES structure is confined to the 5'UTR and is not affected by the viral coding sequence. This is the first report of IRES activity in a fish virus and can give us tools to generate antivirals to attack the virus without affecting fish directly. Copyright © 2017. Published by Elsevier B.V.

Direct access inter-process shared memory

DOEpatents

Brightwell, Ronald B; Pedretti, Kevin; Hudson, Trammell B

2013-10-22

A technique for directly sharing physical memory between processes executing on processor cores is described. The technique includes loading a plurality of processes into the physical memory for execution on a corresponding plurality of processor cores sharing the physical memory. An address space is mapped to each of the processes by populating a first entry in a top level virtual address table for each of the processes. The address space of each of the processes is cross-mapped into each of the processes by populating one or more subsequent entries of the top level virtual address table with the first entry in the top level virtual address table from other processes.

The Polyomaviridae: Contributions of virus structure to our understanding of virus receptors and infectious entry

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

Neu, Ursula; Stehle, Thilo; Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232

This review summarizes the field's major findings related to the characterization of polyomavirus structures and to the characterization of virus receptors and mechanisms of host cell invasion. The four members of the family that have received the most attention in this regard are the mouse polyomavirus (mPyV), the monkey polyomavirus SV40, and the two human polyomaviruses, JCV and BKV. The structures of both the mPyV and SV40 alone and in complex with receptor fragments have been solved to high resolution. The majority of polyomaviruses recognize terminal sialic acid in either an {alpha}2,3 linkage or an {alpha}2,6 linkage to the underlyingmore » galactose. Studies on virus structure, receptor utilization and mechanisms of entry have led to new insights into how these viruses interact in an active way with cells to ensure the nuclear delivery and expression of their genomes. Critical work on virus entry has led to the discovery of a pH neutral endocytic compartment that accepts cargo from caveolae and to novel roles for endoplasmic reticulum (ER) associated factors in virus uncoating and penetration of ER membranes. This review will summarize the major findings and compare and contrast the mechanisms used by these viruses to infect cells.« less

Transient Receptor Potential Channel 1 Deficiency Impairs Host Defense and Proinflammatory Responses to Bacterial Infection by Regulating Protein Kinase Cα Signaling.

PubMed

Zhou, Xikun; Ye, Yan; Sun, Yuyang; Li, Xuefeng; Wang, Wenxue; Privratsky, Breanna; Tan, Shirui; Zhou, Zongguang; Huang, Canhua; Wei, Yu-Quan; Birnbaumer, Lutz; Singh, Brij B; Wu, Min

2015-08-01

Transient receptor potential channel 1 (TRPC1) is a nonselective cation channel that is required for Ca(2+) homeostasis necessary for cellular functions. However, whether TRPC1 is involved in infectious disease remains unknown. Here, we report a novel function for TRPC1 in host defense against Gram-negative bacteria. TRPC1(-/-) mice exhibited decreased survival, severe lung injury, and systemic bacterial dissemination upon infection. Furthermore, silencing of TRPC1 showed decreased Ca(2+) entry, reduced proinflammatory cytokines, and lowered bacterial clearance. Importantly, TRPC1 functioned as an endogenous Ca(2+) entry channel critical for proinflammatory cytokine production in both alveolar macrophages and epithelial cells. We further identified that bacterium-mediated activation of TRPC1 was dependent on Toll-like receptor 4 (TLR4), which induced endoplasmic reticulum (ER) store depletion. After activation of phospholipase Cγ (PLC-γ), TRPC1 mediated Ca(2+) entry and triggered protein kinase Cα (PKCα) activity to facilitate nuclear translocation of NF-κB/Jun N-terminal protein kinase (JNK) and augment the proinflammatory response, leading to tissue damage and eventually mortality. These findings reveal that TRPC1 is required for host defense against bacterial infections through the TLR4-TRPC1-PKCα signaling circuit. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Asthma risk and occupation as a respiratory therapist.

PubMed

Christiani, D C; Kern, D G

1993-09-01

In the modern hospital environment, many health care workers are exposed to hazardous substances. Among these hazards are respiratory sensitizers, irritants, and infectious agents. A previous cross-sectional study of Rhode Island respiratory therapists reported an excess risk of asthma after entry into that profession. Before the results of that study were published, we conducted a confirmatory mailed questionnaire survey of 2,086 Massachusetts respiratory therapists and 2,030 physical therapists and physical therapy assistants. Neither the survey questionnaire nor the accompanying cover letter revealed the focus of our investigation. A history of physician-diagnosed asthma was reported by 16% of respiratory therapists and 8% of control subjects. When analysis was restricted to those who developed asthma after entry into their profession, respiratory therapists still had a significant excess, 7.4 versus 2.8%. The odds ratio for respiratory therapy was 2.5 (95% Cl, 1.6 to 3.3) after adjustment for age, family history, atopic history, smoking, and gender. These results confirm the previous report of excess risk of asthma among respiratory therapists. This excess risk develops after entry into the profession and does not appear to be explained by bias or confounding. Efforts should be directed to identifying potential agents responsible for this form of occupational asthma.

Alanine substitution of conserved residues in the cytoplasmic tail of herpes simplex virus gB can enhance or abolish cell fusion activity and viral entry

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

Ruel, Nancy; Zago, Anna; Spear, Patricia G.

2006-03-01

Herpes simplex virus (HSV) glycoprotein B (gB) is one of the four viral glycoproteins required for viral entry and cell fusion and is highly conserved among herpesviruses. Mutants of HSV type 2 gB were generated by substituting conserved residues in the cytoplasmic tail with alanine or by deleting 41 amino acids from the C-terminus. Some of the mutations abolished cell fusion activity and also prevented transport of gB to the cell surface, identifying residues in the gB cytoplasmic tail that are critical for intracellular transport of this glycoprotein. These mutations also prevented production of infectious virus, possibly because the mutantmore » forms of gB were not transported to the site of envelopment. Other mutations, particularly the deletion, significantly enhanced cell fusion activity. These mutations, as well as others described previously, identify regions of the gB cytoplasmic domain that modulate cell fusion activity.« less

Infectious waste management in Japan: A revised regulation and a management process in medical institutions

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

Miyazaki, M.; Une, H.

In Japan, the waste management practice is carried out in accordance with the Waste Disposal Law of 1970. The first rule of infectious waste management was regulated in 1992, and infectious wastes are defined as the waste materials generated in medical institutions as a result of medical care or research which contain pathogens that have the potential to transmit infectious diseases. Revised criteria for infectious waste management were promulgated by the Ministry of Environment in 2004. Infectious waste materials are divided into three categories: the form of waste; the place of waste generation; the kind of infectious diseases. A reductionmore » of infectious waste is expected. We introduce a summary of the revised regulation of infectious waste management in this article.« less

[Revealing of tuberculosis in an infectious diseases hospital of a megalopolis].

PubMed

Malashenkov, E A; Ivanovskiĭ, V B

2007-01-01

The advisory work of the phthisiatrician in an infectious diseases hospital was analyzed; the analysis revealed that in 2005 tuberculose changes of various degrees of activity had been revealed in 42.5% of examined patients, and 32.1% of them were subjects in whom tuberculosis of diferent localizations had been revealed for the first time. In 43.2% of the latter subjects, the reasons for hospitalization were "clinical masks" of tuberculose process (influenza, acute respiratory viral disease), while 48.6% were hospitalized for gastrointestinal infections and viral hepatitis. In 20.7% of cases tuberculosis was combined with HIV infection. In the infectious diseases hospital, 16.2% of patients with active tuberculosis died. Among the patients treated in the infectious diseases hospital during one year, the proportion of patients with active tuberculosis was 1.44%, the proportion of those in whom the process was revealed for the first time, was 0.75%. In Botkin infectious diseases hospital, there were approximately 6% of patients in whom tuberculose process was revealed for the first time in Saint Petersburg. The peculiarities of this group of patients in an infectious diseases hospital require not only tuberculose alertness, but also reinforcement of phthisiatric, radiological, and laboratory services.

19 CFR 141.18 - Entry by nonresident corporation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry by nonresident corporation. 141.18 Section....18 Entry by nonresident corporation. A nonresident corporation (i.e., one which is not incorporated... entry is located who is authorized to accept service of process against that corporation or, in the case...

19 CFR 141.18 - Entry by nonresident corporation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 2 2011-04-01 2011-04-01 false Entry by nonresident corporation. 141.18 Section....18 Entry by nonresident corporation. A nonresident corporation (i.e., one which is not incorporated... entry is located who is authorized to accept service of process against that corporation or, in the case...

19 CFR 141.18 - Entry by nonresident corporation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 2 2013-04-01 2013-04-01 false Entry by nonresident corporation. 141.18 Section....18 Entry by nonresident corporation. A nonresident corporation (i.e., one which is not incorporated... entry is located who is authorized to accept service of process against that corporation or, in the case...

19 CFR 141.18 - Entry by nonresident corporation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 2 2012-04-01 2012-04-01 false Entry by nonresident corporation. 141.18 Section....18 Entry by nonresident corporation. A nonresident corporation (i.e., one which is not incorporated... entry is located who is authorized to accept service of process against that corporation or, in the case...

19 CFR 141.18 - Entry by nonresident corporation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 2 2014-04-01 2014-04-01 false Entry by nonresident corporation. 141.18 Section....18 Entry by nonresident corporation. A nonresident corporation (i.e., one which is not incorporated... entry is located who is authorized to accept service of process against that corporation or, in the case...

Stakeholder identification of advanced technology opportunities at international ports of entry

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

Parker, S.K.; Icerman, L.

As part of the Advanced Technologies for International and Intermodal Ports of Entry (ATIPE) Project, a diverse group of stakeholders was engaged to help identify problems experienced at inland international border crossings, particularly those at the US-Mexican border. The fundamental issue at international ports of entry is reducing transit time through the required documentation and inspection processes. Examples of other issues or problems, typically manifested as time delays at border crossings, repeatedly mentioned by stakeholders include: (1) lack of document standardization; (2) failure to standardize inspection processes; (3) inadequate information and communications systems; (4) manual fee and tariff collection; (5)more » inconsistency of processes and procedures; and (6) suboptimal cooperation among governmental agencies. Most of these issues can be addressed to some extent by the development of advanced technologies with the objective of allowing ports of entry to become more efficient while being more effective. Three categories of technologies were unambiguously of high priority to port of entry stakeholders: (1) automated documentation; (2) systems integration; and (3) vehicle and cargo tracking. Together, these technologies represent many of the technical components necessary for pre-clearance of freight approaching international ports of entry. Integration of vehicle and cargo tracking systems with port of entry information and communications systems, as well as existing industry legacy systems, should further enable border crossings to be accomplished consistently with optimal processing times.« less

Host Range Restriction of Insect-Specific Flaviviruses Occurs at Several Levels of the Viral Life Cycle.

PubMed

Junglen, Sandra; Korries, Marvin; Grasse, Wolfgang; Wieseler, Janett; Kopp, Anne; Hermanns, Kyra; León-Juárez, Moises; Drosten, Christian; Kümmerer, Beate Mareike

2017-01-01

The genus Flavivirus contains emerging arthropod-borne viruses (arboviruses) infecting vertebrates, as well as insect-specific viruses (ISVs) (i.e., viruses whose host range is restricted to insects). ISVs are evolutionary precursors to arboviruses. Knowledge of the nature of the ISV infection block in vertebrates could identify functions necessary for the expansion of the host range toward vertebrates. Mapping of host restrictions by complementation of ISV and arbovirus genome functions could generate knowledge critical to predicting arbovirus emergence. Here we isolated a novel flavivirus, termed Niénokoué virus (NIEV), from mosquitoes sampled in Côte d'Ivoire. NIEV groups with insect-specific flaviviruses (ISFs) in phylogeny and grows in insect cells but not in vertebrate cells. We generated an infectious NIEV cDNA clone and a NIEV reporter replicon to study growth restrictions of NIEV in comparison to yellow fever virus (YFV), for which the same tools are available. Efficient RNA replication of the NIEV reporter replicon was observed in insect cells but not in vertebrate cells. Initial translation of the input replicon RNA in vertebrate cells was functional, but RNA replication did not occur. Chimeric YFV carrying the envelope proteins of NIEV was recovered via electroporation in C6/36 insect cells but did not infect vertebrate cells, indicating a block at the level of entry. Since the YF/NIEV chimera readily produced infectious particles in insect cells but not in vertebrate cells despite efficient RNA replication, restriction is also determined at the level of assembly/release. Taking the results together, the ability of ISF to infect vertebrates is blocked at several levels, including attachment/entry and RNA replication as well as assembly/release. IMPORTANCE Most viruses of the genus Flavivirus , e.g., YFV and dengue virus, are mosquito borne and transmitted to vertebrates during blood feeding of mosquitoes. Within the last decade, an increasing number of viruses with a host range exclusively restricted to insects in close relationship to the vertebrate-pathogenic flaviviruses were discovered in mosquitoes. To identify barriers that could block the arboviral vertebrate tropism, we set out to identify the steps at which the ISF replication cycle fails in vertebrates. Our studies revealed blocks at several levels, suggesting that flavivirus host range expansion from insects to vertebrates was a complex process that involved overcoming multiple barriers.

Host Range Restriction of Insect-Specific Flaviviruses Occurs at Several Levels of the Viral Life Cycle

PubMed Central

Junglen, Sandra; Korries, Marvin; Grasse, Wolfgang; Wieseler, Janett; Kopp, Anne; Hermanns, Kyra; León-Juárez, Moises; Drosten, Christian

2017-01-01

ABSTRACT The genus Flavivirus contains emerging arthropod-borne viruses (arboviruses) infecting vertebrates, as well as insect-specific viruses (ISVs) (i.e., viruses whose host range is restricted to insects). ISVs are evolutionary precursors to arboviruses. Knowledge of the nature of the ISV infection block in vertebrates could identify functions necessary for the expansion of the host range toward vertebrates. Mapping of host restrictions by complementation of ISV and arbovirus genome functions could generate knowledge critical to predicting arbovirus emergence. Here we isolated a novel flavivirus, termed Niénokoué virus (NIEV), from mosquitoes sampled in Côte d’Ivoire. NIEV groups with insect-specific flaviviruses (ISFs) in phylogeny and grows in insect cells but not in vertebrate cells. We generated an infectious NIEV cDNA clone and a NIEV reporter replicon to study growth restrictions of NIEV in comparison to yellow fever virus (YFV), for which the same tools are available. Efficient RNA replication of the NIEV reporter replicon was observed in insect cells but not in vertebrate cells. Initial translation of the input replicon RNA in vertebrate cells was functional, but RNA replication did not occur. Chimeric YFV carrying the envelope proteins of NIEV was recovered via electroporation in C6/36 insect cells but did not infect vertebrate cells, indicating a block at the level of entry. Since the YF/NIEV chimera readily produced infectious particles in insect cells but not in vertebrate cells despite efficient RNA replication, restriction is also determined at the level of assembly/release. Taking the results together, the ability of ISF to infect vertebrates is blocked at several levels, including attachment/entry and RNA replication as well as assembly/release. IMPORTANCE Most viruses of the genus Flavivirus, e.g., YFV and dengue virus, are mosquito borne and transmitted to vertebrates during blood feeding of mosquitoes. Within the last decade, an increasing number of viruses with a host range exclusively restricted to insects in close relationship to the vertebrate-pathogenic flaviviruses were discovered in mosquitoes. To identify barriers that could block the arboviral vertebrate tropism, we set out to identify the steps at which the ISF replication cycle fails in vertebrates. Our studies revealed blocks at several levels, suggesting that flavivirus host range expansion from insects to vertebrates was a complex process that involved overcoming multiple barriers. PMID:28101536

Entry inhibitors in the treatment of HIV-1 infection.

PubMed

Tilton, John C; Doms, Robert W

2010-01-01

Infection of target cells by HIV is a complex, multi-stage process involving attachment to host cells and CD4 binding, coreceptor binding, and membrane fusion. Drugs that block HIV entry are collectively known as entry inhibitors, but comprise a complex group of drugs with multiple mechanisms of action depending on the stage of the entry process at which they act. Two entry inhibitors, maraviroc and enfuvirtide, have been approved for the treatment of HIV-1 infection, and a number of agents are in development. This review covers the entry inhibitors and their use in the management of HIV-1 infection. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010. Copyright 2009 Elsevier B.V. All rights reserved.

Clinical laboratory waste management in Shiraz, Iran.

PubMed

Askarian, Mehrdad; Motazedian, Nasrin; Palenik, Charles John

2012-06-01

Clinical laboratories are significant generators of infectious waste, including microbiological materials, contaminated sharps, and pathologic wastes such as blood specimens and blood products. Most waste produced in laboratories can be disposed of in the general solid waste stream. However, improper management of infectious waste, including mixing general wastes with infectious wastes and improper handling or storage, could lead to disease transmission. The aim of this study was to assess waste management processes used at clinical laboratories in Shiraz, Iran. One hundred and nine clinical laboratories participated In this cross sectional study, Data collection was by questionnaire and direct observation. Of the total amount of waste generated, 52% (by weight) was noninfectious domestic waste, 43% was non-sharps infectious waste and 5% consisted of sharps. There was no significant relationship between laboratory staff or manager education and the score for quality of waste collection and disposal at clinical laboratories. Improvements in infectious waste management processes should involve clearer, more uniformly accepted definitions of infectious waste and increased staff training.

Entry and Exit.

DTIC Science & Technology

1987-03-01

1. Introduction R Analyses of industrial competition have attained a new vigor with the application of game -theoretic methods. The process of... competition is represented in models that reflect genuine struggles for entry, market power, and continuing survival. Dynamics and informational effects are...presents a few of the models developed recently to study competitive processes that affect a firm’s entry into a market , and the decision to exit. The

40 CFR 63.3176 - What definitions apply to this subpart?

Code of Federal Regulations, 2012 CFR

2012-07-01

... facility which assembles automobiles or light-duty trucks, including coating facilities and processes. Bake oven air seal means an entry or entry vestibule to or an exit or exit vestibule from a bake oven which isolates the bake oven from the area immediately preceding (for an entry or entry vestibule) or immediately...

40 CFR 63.3176 - What definitions apply to this subpart?

Code of Federal Regulations, 2013 CFR

2013-07-01

... facility which assembles automobiles or light-duty trucks, including coating facilities and processes. Bake oven air seal means an entry or entry vestibule to or an exit or exit vestibule from a bake oven which isolates the bake oven from the area immediately preceding (for an entry or entry vestibule) or immediately...

40 CFR 63.3176 - What definitions apply to this subpart?

Code of Federal Regulations, 2014 CFR

2014-07-01

... facility which assembles automobiles or light-duty trucks, including coating facilities and processes. Bake oven air seal means an entry or entry vestibule to or an exit or exit vestibule from a bake oven which isolates the bake oven from the area immediately preceding (for an entry or entry vestibule) or immediately...

DESIGN: a program to create data entry programs

Treesearch

J. Michael Wuerth; David R. Weise

1994-01-01

Scientific data entry can be an exacting process. The specific information needs change from investigation to investigation. A computer program to design custom data screens is described. The program, DESIGN, generates the necessary C programming language source code to create a basic data entry program. Data entry screens can contain multiple nested screens. Users can...

Comparison of reporting phase III randomized controlled trials of antibiotic treatment for common bacterial infections in ClinicalTrials.gov and matched publications.

PubMed

Shepshelovich, D; Yelin, D; Gafter-Gvili, A; Goldman, S; Avni, T; Yahav, D

2018-02-15

Discrepancies between ClinicalTrials.gov entries and matching publications were previously described in general medicine. We aimed to evaluate the consistency of reporting in trials addressing systemic antibiotic therapy. We searched ClinicalTrials.gov for completed phase III trials comparing antibiotic regimens until May 2017. Matched publications were identified in PubMed. Two independent reviewers extracted data and identified inconsistencies. Reporting was assessed among studies started before and after 1 July 2005, when the International Committee of Medical Journal Editors (ICMJE) required mandatory registration as a prerequisite for considering a trial for publication. Matching publications were identified for 75 (70%) of 107 ClinicalTrials.gov entries. Median time from study completion to publication was 26 months (interquartile range 19-42). Primary outcome definition was inconsistent between ClinicalTrials.gov and publications in seven trials (7/72, 10%) and reporting of the primary outcome timeframe was inconsistent in 14 (14/71, 20%). Secondary outcomes definitions were inconsistent in 36 trials (36/66, 55%). Reporting of inclusion criteria and study timeline were inconsistent in 17% (13/65) and 3% (2/65), respectively. Trials started after July 2005 were significantly less likely to have reporting inconsistencies and were published in higher impact factor journals. We found a lower inconsistency rate of outcome reporting compared with other medical disciplines. Reporting completeness and consistency were significantly better after July 2005. The ICMJE requirement for mandatory registration was associated with significant improvement in reporting quality in infectious diseases trials. Prolonged time lag to publication and missing data from unpublished trials should raise a discussion on current reporting and publishing procedures. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Respective Roles of Culturable and Viable-but-Nonculturable Cells in the Heterogeneity of Salmonella enterica Serovar Typhimurium Invasiveness▿

PubMed Central

Passerat, Julien; Got, Patrice; Dukan, Sam; Monfort, Patrick

2009-01-01

The existence of Salmonella enterica serovar Typhimurium viable-but-nonculturable (VBNC) cells is a public health concern since they could constitute unrecognized sources of infection if they retain their pathogenicity. To date, many studies have addressed the ability of S. Typhimurium VBNC cells to remain infectious, but their conclusions are conflicting. An assumption could explain these conflicting results. It has been proposed that infectivity could be retained only temporarily after entry into the VBNC state and that most VBNC cells generated under intense stress could exceed the stage where they are still infectious. Using a Radioselectan density gradient centrifugation technique makes it possible to increase the VBNC-cell/culturable-cell ratio without increasing the exposure to stress and, consequently, to work with a larger proportion of newly VBNC cells. Here, we observed that (i) in the stationary phase, the S. Typhimurium population comprised three distinct subpopulations at 10, 24, or 48 h of culture; (ii) the VBNC cells were detected at 24 and 48 h; (iii) measurement of invasion gene (hilA, invF, and orgA) expression demonstrated that cells are highly heterogeneous within a culturable population; and (iv) invasion assays of HeLa cells showed that culturable cells from the different subpopulations do not display the same invasiveness. The results also suggest that newly formed VBNC cells are either weakly able or not able to successfully initiate epithelial cell invasion. Finally, we propose that at entry into the stationary phase, invasiveness may be one way for populations of S. Typhimurium to escape stochastic alteration leading to cell death. PMID:19525274

Causal Inference Regarding Infectious Aetiology of Chronic Conditions: A Systematic Review

PubMed Central

Orrskog, Sofia; Medin, Emma; Tsolova, Svetla; Semenza, Jan C.

2013-01-01

Background The global burden of disease has shifted from communicable diseases in children to chronic diseases in adults. This epidemiologic shift varies greatly by region, but in Europe, chronic conditions account for 86% of all deaths, 77% of the disease burden, and up to 80% of health care expenditures. A number of risk factors have been implicated in chronic diseases, such as exposure to infectious agents. A number of associations have been well established while others remain uncertain. Methods and Findings We assessed the body of evidence regarding the infectious aetiology of chronic diseases in the peer-reviewed literature over the last decade. Causality was assessed with three different criteria: First, the total number of associations documented in the literature between each infectious agent and chronic condition; second, the epidemiologic study design (quality of the study); third, evidence for the number of Hill's criteria and Koch's postulates that linked the pathogen with the chronic condition. We identified 3136 publications, of which 148 were included in the analysis. There were a total of 75 different infectious agents and 122 chronic conditions. The evidence was strong for five pathogens, based on study type, strength and number of associations; they accounted for 60% of the associations documented in the literature. They were human immunodeficiency virus, hepatitis C virus, Helicobacter pylori, hepatitis B virus, and Chlamydia pneumoniae and were collectively implicated in the aetiology of 37 different chronic conditions. Other pathogens examined were only associated with very few chronic conditions (≤3) and when applying the three different criteria of evidence the strength of the causality was weak. Conclusions Prevention and treatment of these five pathogens lend themselves as effective public health intervention entry points. By concentrating research efforts on these promising areas, the human, economic, and societal burden arising from chronic conditions can be reduced. PMID:23935899

Infectious diseases and securitization: WHO's dilemma.

PubMed

Jin, Jiyong; Karackattu, Joe Thomas

2011-06-01

The threat posed by infectious diseases has been increasingly framed as a security issue. The UN Security Council's Resolution 1308, which designated HIV/AIDS as a threat to international security, evidenced the securitization process. Using securitization theory as a theoretical tool, this article explores the securitization of infectious diseases in the World Health Organization (WHO). While WHO has tended to securitize infectious diseases since 2000, it has encountered a dilemma in the process because of the inherent asymmetry of interest between developed and developing countries. The act of securitization in WHO currently remains mostly a rhetorical device, since WHO's norms emblematic of securitization have not been backed by operational measures for verification or enforcement due to these asymmetric interests.

Injection safety practices in a main referral hospital in Northeastern Nigeria.

PubMed

Gadzama, G B; Bawa, S B; Ajinoma, Z; Saidu, M M; Umar, A S

2014-01-01

No adherence of safe injection policies remains a major challenge, and, worldwide, annually, it leads to 21 million new hepatitis B cases and 260,000 HIV infection cases. This descriptive observational survey was conducted to determine the level of adherence to universal precaution for safe injection practices in the hospital. The study units were selected using a simple random sampling of injection services provider/phlebotomist in 27 units/wards of the hospital. The study instruments were observation checklist and interviewer administered questionnaires. EPI info (version 3.5.2) software was used for data entry and generation of descriptive statistics was done with units of analysis (units/wards) on injection safety practices of health workers, availability of logistics and supplies, and disposal methods. Only 33.3% of the units (95% CI, 16-54) had non-sharps infectious healthcare waste of any type inside containers specific for non-sharps infectious waste and 17 (77.3%) of the observed therapeutic injections were prepared on a clean, dedicated table or tray, where contamination of the equipment with blood, body fluids, or dirty swabs was unlikely. Absence of recapping of needles was observed in 11 (50.0%) units giving therapeutic injections. Only 7.4% of units surveyed had separate waste containers for infectious non-sharps. This study depicts poor knowledge and a practice of injection safety, inadequate injection safety supplies, and non-compliance to injection safety policy and guidelines.

Capacity building in pediatric transplant infectious diseases: an international perspective.

PubMed

Danziger-Isakov, Lara; Evans, Helen M; Green, Michael; McCulloch, Mignon; Michaels, Marian G; Posfay-Barbe, Klara M; Verma, Anita; Allen, Upton

2014-12-01

Transplant infectious diseases is a rapidly emerging subspecialty within pediatric infectious diseases reflecting the increasing volumes and complexity of this patient population. Incorporating transplant infectious diseases into the transplant process would provide an opportunity to improve clinical outcome and advocacy as well as expand research. The relationship between transplant physicians and infectious diseases (ID) specialists is one of partnership, collaboration, and mutual continuing professional education. The ID CARE Committee of the International Pediatric Transplant Association (IPTA) views the development and integration of transplant infectious diseases into pediatric transplant care as an international priority. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mad dogs, vampires, and zombie ants: a multidisciplinary approach to teaching neuroscience, behavior, and microbiology.

PubMed

Esteban, David J; Holloway, Kevin S

2015-01-01

Viruses, parasites, and some bacteria use host organisms to complete their lifecycle. These infectious agents are able to hijack host processes to replicate and transmit to the next host. While we tend to think of infections as just making us sick, they are also capable of changing host behavior. In fact, many infectious agents are able to mediate host behavior in ways that can enhance transmission of the disease. In this course we explore the process of host behavior mediation by infectious agents, combining aspects of multiple fields including neurobiology, animal behavior, infectious disease microbiology, and epidemiology. The goals for this course are: 1) To explore the neurological and behavioral effects of infectious organisms on their hosts, in particular pathogen mediation of host behavior to the benefit of the pathogen, 2) to introduce students to primary literature in a multidisciplinary field, and 3) when applicable, to address cultural/historical/mythological perspectives that might alter societal norms and pressures and influence the impact of the biological processes of behavior modification by infections.

Mad Dogs, Vampires, and Zombie Ants: A Multidisciplinary Approach to Teaching Neuroscience, Behavior, and Microbiology

PubMed Central

Esteban, David J.; Holloway, Kevin S.

2015-01-01

Viruses, parasites, and some bacteria use host organisms to complete their lifecycle. These infectious agents are able to hijack host processes to replicate and transmit to the next host. While we tend to think of infections as just making us sick, they are also capable of changing host behavior. In fact, many infectious agents are able to mediate host behavior in ways that can enhance transmission of the disease. In this course we explore the process of host behavior mediation by infectious agents, combining aspects of multiple fields including neurobiology, animal behavior, infectious disease microbiology, and epidemiology. The goals for this course are: 1) To explore the neurological and behavioral effects of infectious organisms on their hosts, in particular pathogen mediation of host behavior to the benefit of the pathogen, 2) to introduce students to primary literature in a multidisciplinary field, and 3) when applicable, to address cultural/historical/mythological perspectives that might alter societal norms and pressures and influence the impact of the biological processes of behavior modification by infections. PMID:25838806

The Design Process of Physical Security as Applied to a U.S. Border Point of Entry

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

Wagner, G.G.

1998-10-26

This paper describes the design process of physical security as applied to a U.S. Border Port of Entry (PoE). Included in this paper are descriptions of the elements that compose U.S. border security. The physical security design will describe the various elements that make up the process as well as the considerations that must be taken into account when dealing with system integration of those elements. The distinctions between preventing unlawful entry and exit of illegal contraband will be emphasized.

Disease in the Society: Infectious Cadavers Result in Collapse of Ant Sub-Colonies.

PubMed

Loreto, Raquel G; Hughes, David P

2016-01-01

Despite the growing number of experimental studies on mechanisms of social immunity in ant societies, little is known about how social behavior relates to disease progression within the nests of ants. In fact, when empirically studying disease in ant societies, it is common to remove dead ants from experiments to confirm infection by the studied parasite. This unfortunately does not allow disease to progress within the nest as it may be assumed would happen under natural conditions. Therefore, the approach taken so far has resulted in a limited knowledge of diseases dynamics within the nest environment. Here we introduced a single infectious cadaver killed by the fungus Beauveria bassiana into small nests of the ant Camponotus castaneus. We then observed the natural progression of the disease by not removing the corpses of the ants that died following the first entry of the disease. Because some behaviors such as social isolation of sick individuals or the removal of cadavers by nestmates are considered social immune functions and thus adaptations at the colony level that reduce disease spread, we also experimentally confined some sub-colonies to one or two chamber nests to prevent the expression of such behaviors. Based on 51 small nests and survival studies in 1,003 ants we found that a single introduced infectious cadaver was able to transmit within the nest, and social immunity did not prevent the collapse of the small sub-colonies here tested. This was true whether ants did or did not have the option to remove the infectious cadaver. Therefore, we found no evidence that the typically studied social immunity behaviors can reduce disease spread in the conditions here tested.

Disease in the Society: Infectious Cadavers Result in Collapse of Ant Sub-Colonies

PubMed Central

Loreto, Raquel G.; Hughes, David P.

2016-01-01

Despite the growing number of experimental studies on mechanisms of social immunity in ant societies, little is known about how social behavior relates to disease progression within the nests of ants. In fact, when empirically studying disease in ant societies, it is common to remove dead ants from experiments to confirm infection by the studied parasite. This unfortunately does not allow disease to progress within the nest as it may be assumed would happen under natural conditions. Therefore, the approach taken so far has resulted in a limited knowledge of diseases dynamics within the nest environment. Here we introduced a single infectious cadaver killed by the fungus Beauveria bassiana into small nests of the ant Camponotus castaneus. We then observed the natural progression of the disease by not removing the corpses of the ants that died following the first entry of the disease. Because some behaviors such as social isolation of sick individuals or the removal of cadavers by nestmates are considered social immune functions and thus adaptations at the colony level that reduce disease spread, we also experimentally confined some sub-colonies to one or two chamber nests to prevent the expression of such behaviors. Based on 51 small nests and survival studies in 1,003 ants we found that a single introduced infectious cadaver was able to transmit within the nest, and social immunity did not prevent the collapse of the small sub-colonies here tested. This was true whether ants did or did not have the option to remove the infectious cadaver. Therefore, we found no evidence that the typically studied social immunity behaviors can reduce disease spread in the conditions here tested. PMID:27529548

Impact of Active Metabolism on Chlamydia trachomatis Elementary Body Transcript Profile and Infectivity.

PubMed

Grieshaber, Scott; Grieshaber, Nicole; Yang, Hong; Baxter, Briana; Hackstadt, Ted; Omsland, Anders

2018-07-15

Bacteria of the genus Chlamydia include the significant human pathogens Chlamydia trachomatis and C. pneumoniae All chlamydiae are obligate intracellular parasites that depend on infection of a host cell and transition through a biphasic developmental cycle. Following host cell invasion by the infectious elementary body (EB), the pathogen transitions to the replicative but noninfectious reticulate body (RB). Differentiation of the RB back to the EB is essential to generate infectious progeny. While the EB form has historically been regarded as metabolically inert, maintenance of infectivity during incubation with specific nutrients has revealed active maintenance of the infectious phenotype. Using transcriptome sequencing, we show that the transcriptome of extracellular EBs incubated under metabolically stimulating conditions does not cluster with germinating EBs but rather with the transcriptome of EBs isolated directly from infected cells. In addition, the transcriptional profile of the extracellular metabolizing EBs more closely resembled that of EB production than germination. Maintenance of infectivity of extracellular EBs was achieved by metabolizing chemically diverse compounds, including glucose 6-phosphate, ATP, and amino acids, all of which can be found in extracellular environments, including mucosal secretions. We further show that the EB cell type actively maintains infectivity in the inclusion after terminal differentiation. Overall, these findings contribute to the emerging understanding that the EB cell form is actively maintained through metabolic processes after terminal differentiation to facilitate prolonged infectivity within the inclusion and under host cell free conditions, for example, following deposition at mucosal surfaces. IMPORTANCE Chlamydiae are obligate intracellular Gram-negative bacteria that are responsible for a wide range of diseases in both animal and human hosts. According to the Centers for Disease Control and Prevention, C. trachomatis is the most frequently reported sexually transmitted infection in the United States, costing the American health care system nearly $2.4 billion annually. Every year, there are over 4 million new cases of Chlamydia infections in the United States and an estimated 100 million cases worldwide. To cause disease, Chlamydia must successfully complete its complex biphasic developmental cycle, alternating between an infectious cell form (EB) specialized for initiating entry into target cells and a replicative form (RB) specialized for creating and maintaining the intracellular replication niche. The EB cell form has historically been considered metabolically quiescent, a passive entity simply waiting for contact with a host cell to initiate the next round of infection. Recent studies and data presented here demonstrate that the EB maintains its infectious phenotype by actively metabolizing a variety of nutrients. Therefore, the EB appears to have an active role in chlamydial biology, possibly within multiple environments, such as mucosal surfaces, fomites, and inside the host cell after formation. Copyright © 2018 American Society for Microbiology.

Cellular Antiviral Factors that Target Particle Infectivity of HIV-1.

PubMed

Goffinet, Christine

2016-01-01

In the past decade, the identification and characterization of antiviral genes with the ability to interfere with virus replication has established cell-intrinsic innate immunity as a third line of antiviral defense in addition to adaptive and classical innate immunity. Understanding how cellular factors have evolved to inhibit HIV-1 reveals particularly vulnerable points of the viral replication cycle. Many, but not all, antiviral proteins share type I interferon-upregulated expression and sensitivity to viral counteraction or evasion measures. Whereas well-established restriction factors interfere with early post-entry steps and release of HIV-1, recent research has revealed a diverse set of proteins that reduce the infectious quality of released particles using individual, to date poorly understood modes of action. These include induction of paucity of mature glycoproteins in nascent virions or self-incorporation into the virus particle, resulting in poor infectiousness of the virion and impaired spread of the infection. A better understanding of these newly discovered antiviral factors may open new avenues towards the design of drugs that repress the spread of viruses whose genomes have already integrated.

Standard work for room entry: Linking lean, hand hygiene, and patient-centeredness.

PubMed

O'Reilly, Kristin; Ruokis, Samantha; Russell, Kristin; Teves, Tim; DiLibero, Justin; Yassa, David; Berry, Hannah; Howell, Michael D

2016-03-01

Healthcare-associated infections are costly and fatal. Substantial front-line, administrative, regulatory, and research efforts have focused on improving hand hygiene. While broad agreement exists that hand hygiene is the most important single approach to infection prevention, compliance with hand hygiene is typically only about 40%(1). Our aim was to develop a standard process for room entry in the intensive care unit that improved compliance with hand hygiene and allowed for maximum efficiency. We recognized that hand hygiene is a single step in a substantially more complicated process of room entry. We applied Lean engineering techniques to develop a standard process that included both physical steps and also standard communication elements from provider to patients and families and created a physical environment to support this. We observed meaningful improvement in the performance of the new standard as well as time savings for clinical providers with each room entry. We also observed an increase in room entries that included verbal communication and an explanation of what the clinician was entering the room to do. The design and implementation of a standardized room entry process and the creation of an environment that supports that new process has resulted in measurable positive outcomes on the medical intensive care unit, including quality, patient experience, efficiency, and staff satisfaction. Designing a process, rather than viewing tasks that need to happen in close proximity in time (either serially or in parallel) as unrelated, simplifies work for staff and results in higher compliance to individual tasks. Copyright © 2015 Elsevier Inc. All rights reserved.

19 CFR 142.45 - Use of bar code by entry filer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Use of bar code by entry filer. 142.45 Section 142... THE TREASURY (CONTINUED) ENTRY PROCESS Line Release § 142.45 Use of bar code by entry filer. (a... with instructions from the port director, shall preprint invoices with the C-4 Code in bar code and...

[The life cycle of Rubella Virus].

PubMed

Sakata, Masafumi; Mori, Yoshio

2014-01-01

Rubella virus (RV), an infectious agent of rubella, is the sole member of the genus Rubivirus in the family of Togaviridae. RV has a positive-stranded sense RNA as a genome. A natural host of RV is limited to human, and rubella is considered to be a childhood disease in general. When woman is infected with RV during early pregnancy, her fetus may develop severe birth defects known as congenital rubella syndrome. In this review, the RV life cycle from the virus entry to budding is illustrated in comparison with those of member viruses of the genus alphavirus in the same family. The multiple functions of the RV capsid protein are also introduced.

EDGE 2017 R&D 100 Entry with Appendix

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

Chain, Patrick Sam Guy; Davenport, Karen Walston; Li, Po-E

Diabetes, infertility, cancer, and Alzheimer’s disease—the key to one day preventing or even curing such afflictions and diseases (both infectious and genetically driven) may be locked in our own genetic code and the code of microorganisms that inhabit our bodies. The study of this code, known as genomics, has recently become much more promising as a result of two things: (1) vast improvements in high-throughput, nextgeneration sequencing (NSG), and (2) an exponential decrease in the cost of such sequencing. For example, it originally cost approximately $3 billion to sequence the human genome; today, this genome could be resequenced for lessmore » than $1,000.« less

Mars Entry Atmospheric Data System Trajectory Reconstruction Algorithms and Flight Results

NASA Technical Reports Server (NTRS)

Karlgaard, Christopher D.; Kutty, Prasad; Schoenenberger, Mark; Shidner, Jeremy; Munk, Michelle

2013-01-01

The Mars Entry Atmospheric Data System is a part of the Mars Science Laboratory, Entry, Descent, and Landing Instrumentation project. These sensors are a system of seven pressure transducers linked to ports on the entry vehicle forebody to record the pressure distribution during atmospheric entry. These measured surface pressures are used to generate estimates of atmospheric quantities based on modeled surface pressure distributions. Specifically, angle of attack, angle of sideslip, dynamic pressure, Mach number, and freestream atmospheric properties are reconstructed from the measured pressures. Such data allows for the aerodynamics to become decoupled from the assumed atmospheric properties, allowing for enhanced trajectory reconstruction and performance analysis as well as an aerodynamic reconstruction, which has not been possible in past Mars entry reconstructions. This paper provides details of the data processing algorithms that are utilized for this purpose. The data processing algorithms include two approaches that have commonly been utilized in past planetary entry trajectory reconstruction, and a new approach for this application that makes use of the pressure measurements. The paper describes assessments of data quality and preprocessing, and results of the flight data reduction from atmospheric entry, which occurred on August 5th, 2012.

Numerical and experimental study of the thermal degradation process during the atmospheric re-entry of a TiAl6V4 tank

NASA Astrophysics Data System (ADS)

Prévereaud, Y.; Vérant, J.-L.; Balat-Pichelin, M.; Moschetta, J.-M.

2016-05-01

To answer the question of space debris survivability during atmospheric entry ONERA uses its software named MUSIC/FAST. So, the first part of this paper is dedicated to the presentation of the ONERA tool and its validation by comparison with flight data and CFD computations. However, the influence of oxidation on the thermal degradation process and material properties in atmospheric entry conditions is still unknown. A second step is then devoted to the presentation of an experimental campaign investigating TA6V oxidation in atmospheric entry conditions, as the most of the debris found on ground are made of this material. Experiments have been realized using the MESOX facility implemented at the 6 kW solar furnace in PROMES-CNRS laboratory. Finally, an application of MUSIC/FAST is proposed on the atmospheric re-entry of a generic TA6V tank. Aiming at degradation assessment, a sensitive study to initial conditions is conducted. To complete computational analysis regarding degradation process by melting, a numerical analysis of the influence of oxidation on the thermal wall degradation during the tank atmospheric re-entry is presented as well.

CD4+ T Cells Coexpressing CD134 (OX40) Harbor Significantly Increased Levels of Human Herpesvirus 6B DNA Following Umbilical Cord Blood Transplantation.

PubMed

Pritchett, Joshua C; Green, Jaime S; Thomm, Angela M; Knox, Konstance K; Verneris, Michael R; Lund, Troy C

2016-12-15

Human herpesvirus 6B (HHV-6B) commonly reactivates after umbilical cord blood transplantation (UCBT) and is associated with delayed engraftment, fever, rash, and central nervous system dysfunction. Recently, CD134 (OX40) has been implicated as a potential viral entry receptor. We evaluated CD4 + CD134 + / neg-lo and CD8 + CD134 + / neg-lo cells at day 28 after UCBT in 20 subjects with previously documented HHV-6 reactivation and persistent viremia. Analysis of CD4 + CD134 + cells as compared to CD4 + CD134 neg-lo cells showed 0.308 versus 0.129 copies of HHV-6B/cell (P = .0002). CD8 + CD134 +/neg-lo cells contained little to no HHV-6B copies. Following UCBT, CD4 + CD134 + cells harbor significantly increased levels of HHV-6B, suggesting that CD134 (OX40) may facilitate viral entry. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

The neutralizing antibody response to the vaccinia virus A28 protein is specifically enhanced by its association with the H2 protein

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

Shinoda, Kaori; Wyatt, Linda S.; Moss, Bernard, E-mail: bmoss@niaid.nih.go

2010-09-15

The vaccinia virus (VACV) entry-fusion complex (EFC) is composed of at least nine membrane proteins. Immunization of mice with individual EFC genes induced corresponding protein-binding antibody but failed to protect against VACV intranasal challenge and only DNA encoding A28 elicited low neutralizing antibody. Because the A28 and H2 proteins interact, we determined the effect of immunizing with both genes simultaneously. This procedure greatly enhanced the amount of antibody that bound intact virions, neutralized infectivity, and provided partial protection against respiratory challenge. Neither injection of A28 and H2 plasmids at different sites or mixing A28 and H2 sera enhanced neutralizing antibody.more » The neutralizing antibody could be completely removed by binding to the A28 protein alone and the epitope was located in the C-terminal segment. These data suggest that the interaction of H2 with A28 stabilizes the immunogenic form of A28, mimicking an exposed region of the entry-fusion complex on infectious virions.« less

21 CFR 1270.31 - Written procedures.

Code of Federal Regulations, 2011 CFR

2011-04-01

... procedures prepared and followed for all significant steps in the infectious disease testing process under... procedures prepared, validated, and followed for prevention of infectious disease contamination or cross...

21 CFR 1270.31 - Written procedures.

Code of Federal Regulations, 2012 CFR

2012-04-01

... procedures prepared and followed for all significant steps in the infectious disease testing process under... procedures prepared, validated, and followed for prevention of infectious disease contamination or cross...

21 CFR 1270.31 - Written procedures.

Code of Federal Regulations, 2014 CFR

2014-04-01

... procedures prepared and followed for all significant steps in the infectious disease testing process under... procedures prepared, validated, and followed for prevention of infectious disease contamination or cross...

21 CFR 1270.31 - Written procedures.

Code of Federal Regulations, 2013 CFR

2013-04-01

... procedures prepared and followed for all significant steps in the infectious disease testing process under... procedures prepared, validated, and followed for prevention of infectious disease contamination or cross...

Small molecule inhibitors of the annexin A2 heterotetramer prevent human papillomavirus type 16 infection.

PubMed

Woodham, Andrew W; Taylor, Julia R; Jimenez, Andrew I; Skeate, Joseph G; Schmidt, Thomas; Brand, Heike E; Da Silva, Diane M; Kast, W Martin

2015-01-01

High-risk human papillomavirus (HPV) infection leads to the development of several human cancers that cause significant morbidity and mortality worldwide. HPV type 16 (HPV16) is the most common of the cancer-causing genotypes and gains entry to the basal cells of the epithelium through a non-canonical endocytic pathway that involves the annexin A2/S100A10 heterotetramer (A2t). A2t is composed of two annexin A2 monomers bound to an S100A10 dimer and this interaction is a potential target to block HPV16 infection. Here, recently identified small molecule inhibitors of A2t (A2ti) were investigated for their ability to prevent HPV16 infection in vitro. A2ti were added to HeLa cells in increasing concentrations prior to the addition of HPV16. Cytotoxicity was evaluated via trypan blue exclusion. HPV16 pseudovirion infection and fluorescently labelled HPV16 capsid internalization was measured with flow cytometry. A2ti blocked HPV16 infection by 100% without substantial cellular toxicity or reduction in cell growth. Furthermore, A2ti blocked HPV16 entry into epithelial cells by 65%, indicating that the observed inhibition of HPV16 infection is in part due to a block in entry and that non-infectious entry may occur in the absence of A2t binding. These results demonstrate that targeting A2t may be an effective strategy to prevent HPV16 infection. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Electronic Chemotherapy Order Entry: A Major Cancer Center's Implementation

PubMed Central

Sklarin, Nancy T.; Granovsky, Svetlana; O'Reilly, Eileen M.; Zelenetz, Andrew D.

2011-01-01

Implementation of a computerized provider order entry system for complex chemotherapy regimens at a large cancer center required intense effort from a multidisciplinary team of clinical and systems experts with experience in all facets of the chemotherapy process. The online tools had to resemble the paper forms used at the time and parallel the successful established process as well as add new functionality. Close collaboration between the institution and the vendor was necessary. This article summarizes the institutional efforts, challenges, and collaborative processes that facilitated universal chemotherapy computerized electronic order entry across multiple sites during a period of several years. PMID:22043182

Electronic Chemotherapy Order Entry: A Major Cancer Center's Implementation.

PubMed

Sklarin, Nancy T; Granovsky, Svetlana; O'Reilly, Eileen M; Zelenetz, Andrew D

2011-07-01

Implementation of a computerized provider order entry system for complex chemotherapy regimens at a large cancer center required intense effort from a multidisciplinary team of clinical and systems experts with experience in all facets of the chemotherapy process. The online tools had to resemble the paper forms used at the time and parallel the successful established process as well as add new functionality. Close collaboration between the institution and the vendor was necessary. This article summarizes the institutional efforts, challenges, and collaborative processes that facilitated universal chemotherapy computerized electronic order entry across multiple sites during a period of several years.

Variations in the quality of inpatient rehabilitation care to facilitate school re-entry and cognitive and communication function for children with TBI.

PubMed

Ennis, Stephanie K; Rivara, Frederick P; Mangione-Smith, Rita; Konodi, Mark A; Mackenzie, Ellen J; Jaffe, Kenneth M

2013-01-01

To examine variations in processes of paediatric inpatient rehabilitation care related to school re-entry and management of cognitive and communication impairments after traumatic brain injury. Retrospective cohort study. Adherence to care processes recommended for children (aged 0-17) with moderate-to-severe traumatic brain injury and admitted for inpatient rehabilitation was assessed. Quality-of-care indicators for processes supporting school re-entry and cognitive and communication rehabilitation were applied to measure variations in care delivered to 174 children across nine facilities using medical record review. Adherence rates (the number of times recommended care was delivered or attempted divided by the number of times care was indicated) were calculated, revealing substantial variations in care within and between facilities. Overall, children received 51.3% (95% CI = 31.9-70.7) and 72.3% (95% CI = 61.1-83.5), of the care recommended for school re-entry and cognitive and communication rehabilitation, respectively. Substantial variations exist in the delivery of paediatric inpatient rehabilitation care processes for managing school re-entry and cognitive and communication impairments after traumatic brain injury. Measures of association of these care processes with patient outcomes are necessary. Reduction in this variation is essential to improving quality of care.

Semi-Formal Description of KVM/370 Trusted Processes

DTIC Science & Technology

1977-12-09

OF KVM/370 TRUSTED PROCESSES 9I OTICD. H. THOMPSON SELECTEU JAN 5 IM8 , 9 DECEMBER 1977 D CLEARED FOR OPEN...Record Process TM-6062/111/00 OP15a: Start (Re der) given: Raddr: DeviceAddress NewClasses: set of Class entry: for some (R:ReaderEmtry) In Readers...Corporatio PRPU1: Process request for output spooling device assignment given: Process : ProcessName RequestedClassest set of Class entry: true error on for

The Design Process of Physical Security as Applied to a U.S. Border Port of Entry

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

Wagner, G.G.

1999-02-22

This paper details the application of a standard physical security system design process to a US Border Port of Entry (PoE) for vehicle entry/exit. The physical security design methodology is described as well as the physical security similarities to facilities currently at a US Border PoE for vehicles. The physical security design process description includes the various elements that make up the methodologies well as the considerations that must be taken into account when dealing with system integration of those elements. The distinctions between preventing unlawful entry/exit of illegal contraband and personnel are described. The potential to enhance the functionsmore » of drug/contraband detection in the Pre-Primary Inspection area through the application of emerging technologies are also addressed.« less

Analyzing structural changes in SNOMED CT's Bacterial infectious diseases using a visual semantic delta.

PubMed

Ochs, Christopher; Case, James T; Perl, Yehoshua

2017-03-01

Thousands of changes are applied to SNOMED CT's concepts during each release cycle. These changes are the result of efforts to improve or expand the coverage of health domains in the terminology. Understanding which concepts changed, how they changed, and the overall impact of a set of changes is important for editors and end users. Each SNOMED CT release comes with delta files, which identify all of the individual additions and removals of concepts and relationships. These files typically contain tens of thousands of individual entries, overwhelming users. They also do not identify the editorial processes that were applied to individual concepts and they do not capture the overall impact of a set of changes on a subhierarchy of concepts. In this paper we introduce a methodology and accompanying software tool called a SNOMED CT Visual Semantic Delta ("semantic delta" for short) to enable a comprehensive review of changes in SNOMED CT. The semantic delta displays a graphical list of editing operations that provides semantics and context to the additions and removals in the delta files. However, there may still be thousands of editing operations applied to a set of concepts. To address this issue, a semantic delta includes a visual summary of changes that affected sets of structurally and semantically similar concepts. The software tool for creating semantic deltas offers views of various granularities, allowing a user to control how much change information they view. In this tool a user can select a set of structurally and semantically similar concepts and review the editing operations that affected their modeling. The semantic delta methodology is demonstrated on SNOMED CT's Bacterial infectious disease subhierarchy, which has undergone a significant remodeling effort over the last two years. Copyright © 2017 Elsevier Inc. All rights reserved.

Analyzing Structural Changes in SNOMED CT’s Bacterial Infectious Diseases Using a Visual Semantic Delta

PubMed Central

Ochs, Christopher; Case, James T.; Perl, Yehoshua

2017-01-01

Thousands of changes are applied to SNOMED CT’s concepts during each release cycle. These changes are the result of efforts to improve or expand the coverage of health domains in the terminology. Understanding which concepts changed, how they changed, and the overall impact of a set of changes is important for editors and end users. Each SNOMED CT release comes with delta files, which identify all of the individual additions and removals of concepts and relationships. These files typically contain tens of thousands of individual entries, overwhelming users. They also do not identify the editorial processes that were applied to individual concepts and they do not capture the overall impact of a set of changes on a subhierarchy of concepts. In this paper we introduce a methodology and accompanying software tool called a SNOMED CT Visual Semantic Delta (“semantic delta” for short) to enable a comprehensive review of changes in SNOMED CT. The semantic delta displays a graphical list of editing operations that provides semantics and context to the additions and removals in the delta files. However, there may still be thousands of editing operations applied to a set of concepts. To address this issue, a semantic delta includes a visual summary of changes that affected sets of structurally and semantically similar concepts. The software tool for creating semantic deltas offers views of various granularities, allowing a user to control how much change information they view. In this tool a user can select a set of structurally and semantically similar concepts and review the editing operations that affected their modeling. The semantic delta methodology is demonstrated on SNOMED CT’s Bacterial infectious disease subhierarchy, which has undergone a significant remodeling effort over the last two years. PMID:28215561

Waste Water Management and Infectious Disease. Part II: Impact of Waste Water Treatment

ERIC Educational Resources Information Center

Cooper, Robert C.

1975-01-01

The ability of various treatment processes, such as oxidation ponds, chemical coagulation and filtration, and the soil mantle, to remove the agents of infectious disease found in waste water is discussed. The literature concerning the efficiency of removal of these organisms by various treatment processes is reviewed. (BT)

Mitigation strategies to reduce the generation and transmission of airborne highly pathogenic avian influenza virus particles during processing of infected poultry.

PubMed

Bertran, Kateri; Clark, Andrew; Swayne, David E

2018-06-08

Airborne transmission of H5N1 highly pathogenic avian influenza (HPAI) viruses has occurred among poultry and from poultry to humans during home or live-poultry market slaughter of infected poultry, and such transmission has been experimentally reproduced. In this study, we investigated simple, practical changes in the processing of H5N1 virus-infected chickens to reduce infectious airborne particles and their transmission. Our findings suggest that containing the birds during the killing and bleeding first step by using a disposable plastic bag, a commonly available cooking pot widely used in Egypt (halla), or a bucket significantly reduces generation of infectious airborne particles and transmission to ferrets. Similarly, lack of infectious airborne particles was observed when processing vaccinated chickens that had been challenged with HPAI virus. Moreover, the use of a mechanical defeatherer significantly increased total number of particles in the air compared to manual defeathering. This study confirms that simple changes in poultry processing can efficiently mitigate generation of infectious airborne particles and their transmission to humans. Published by Elsevier GmbH.

Implementation of a pharmacist-led antimicrobial management team in a community teaching hospital: use of pharmacy residents and pharmacy students in a prospective audit and feedback approach.

PubMed

Laible, Brad R; Nazir, Jawad; Assimacopoulos, Aris P; Schut, Jennifer

2010-12-01

Antimicrobial stewardship is an important process proven to combat antimicrobial resistance, improve patient outcomes, and reduce costs. The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) have provided guidelines for the provision of antimicrobial stewardship. According to these recommendations, antimicrobial stewardship teams should be multidisciplinary in nature, with core members consisting of an infectious disease physician and an infectious disease-trained clinical pharmacist. Due to limited resources, our institution chose to implement a pharmacist-led antimicrobial stewardship service on 1 medical/surgical ward, with the existing clinical pharmacist and 3 infectious disease physicians as core members. This clinical pharmacist was not trained in infectious disease specialty, and stewardship activities were only one part of his daily activities. Pharmacy residents and students were extensively utilized to assist in the stewardship process. Approximately two thirds of stewardship recommendations were accepted using primarily a prospective audit and feedback approach.

An approach to and web-based tool for infectious disease outbreak intervention analysis

NASA Astrophysics Data System (ADS)

Daughton, Ashlynn R.; Generous, Nicholas; Priedhorsky, Reid; Deshpande, Alina

2017-04-01

Infectious diseases are a leading cause of death globally. Decisions surrounding how to control an infectious disease outbreak currently rely on a subjective process involving surveillance and expert opinion. However, there are many situations where neither may be available. Modeling can fill gaps in the decision making process by using available data to provide quantitative estimates of outbreak trajectories. Effective reduction of the spread of infectious diseases can be achieved through collaboration between the modeling community and public health policy community. However, such collaboration is rare, resulting in a lack of models that meet the needs of the public health community. Here we show a Susceptible-Infectious-Recovered (SIR) model modified to include control measures that allows parameter ranges, rather than parameter point estimates, and includes a web user interface for broad adoption. We apply the model to three diseases, measles, norovirus and influenza, to show the feasibility of its use and describe a research agenda to further promote interactions between decision makers and the modeling community.

What systems participants know about access and service entry and why managers should listen.

PubMed

Duncombe, Rohena

2017-08-01

Objective The present study looked at the views of people directly involved in the entry process for community health counselling using the frame of the health access literature. The concurrence of system participants' views with the access literature highlights access issues, particularly for people who are vulnerable or disadvantaged. The paper privileges the voices of the system participants, inviting local health services to consider using participatory design to improve access at the entry point. Methods People involved in the entry process for community health counselling explored the question, 'What, for you, are the features of a good intake system?' They also commented on themes identified during pilot interviews. These were thematically analysed for each participant group by the researcher to develop a voice for each stakeholder group. Results People accessing the service could be vulnerable and the entry process failed to take that into account. People directly involved in the counselling service entry system, system participants, consisted of: professionals referring in, people seeking services and reception staff taking first enquiries. They shared substantially the same concerns as each other. The responses from these system participants are consistent with the international literature on access and entry into health services. Conclusion Participatory service design could improve primary healthcare service entry at the local level. Canvassing the experiences of system participants is important for delivering services to those who have the least access and, in that way, could contribute to health equity. What is known about the topic? People with the highest health needs receive the fewest services. Health inequality is increasing. What does this paper add? System participants can provide advice consistent with the academic research literature that is useful for improving service entry at the local level. What are the implications for practitioners? Participatory design can inform policy makers and service providers. Entry systems could acknowledge the potential vulnerability or disadvantage of people approaching the service.

Incoming human papillomavirus 16 genome is lost in PML protein-deficient HaCaT keratinocytes.

PubMed

Bienkowska-Haba, Malgorzata; Luszczek, Wioleta; Keiffer, Timothy R; Guion, Lucile G M; DiGiuseppe, Stephen; Scott, Rona S; Sapp, Martin

2017-05-01

Human papillomaviruses (HPVs) target promyelocytic leukemia (PML) nuclear bodies (NBs) during infectious entry and PML protein is important for efficient transcription of incoming viral genome. However, the transcriptional down regulation was shown to be promoter-independent in that heterologous promoters delivered by papillomavirus particles were also affected. To further investigate the role of PML protein in HPV entry, we used small hairpin RNA to knockdown PML protein in HaCaT keratinocytes. Confirming previous findings, PML knockdown in HaCaT cells reduced HPV16 transcript levels significantly following infectious entry without impairing binding and trafficking. However, when we quantified steady-state levels of pseudogenomes in interphase cells, we found strongly reduced genome levels compared with parental HaCaT cells. Because nuclear delivery was comparable in both cell lines, we conclude that viral pseudogenome must be removed after successful nuclear delivery. Transcriptome analysis by gene array revealed that PML knockdown in clonal HaCaT cells was associated with a constitutive interferon response. Abrogation of JAK1/2 signaling prevented genome loss, however, did not restore viral transcription. In contrast, knockdown of PML protein in HeLa cells did not affect HPV genome delivery and transcription. HeLa cells are transformed by HPV18 oncogenes E6 and E7, which have been shown to interfere with the JAK/Stat signaling pathway. Our data imply that PML NBs protect incoming HPV genomes. Furthermore, they provide evidence that PML NBs are key regulators of the innate immune response in keratinocytes. Promyelocytic leukemia nuclear bodies (PML NBs) are important for antiviral defense. Many DNA viruses target these subnuclear structures and reorganize them. Reorganization of PML NBs by viral proteins is important for establishment of infection. In contrast, HPVs require the presence of PML protein for efficient transcription of incoming viral genome. Our finding that PML protein prevents the loss of HPV genome following infection implies that the host cell may be able to recognize chromatinized HPV genome or the associated capsid proteins. A constitutively active interferon response in absence of PML protein suggests that PML NBs are key regulators of the innate immune response in keratinocytes. © 2016 John Wiley & Sons Ltd.

Sealife: a semantic grid browser for the life sciences applied to the study of infectious diseases.

PubMed

Schroeder, Michael; Burger, Albert; Kostkova, Patty; Stevens, Robert; Habermann, Bianca; Dieng-Kuntz, Rose

2006-01-01

The objective of Sealife is the conception and realisation of a semantic Grid browser for the life sciences, which will link the existing Web to the currently emerging eScience infrastructure. The SeaLife Browser will allow users to automatically link a host of Web servers and Web/Grid services to the Web content he/she is visiting. This will be accomplished using eScience's growing number of Web/Grid Services and its XML-based standards and ontologies. The browser will identify terms in the pages being browsed through the background knowledge held in ontologies. Through the use of Semantic Hyperlinks, which link identified ontology terms to servers and services, the SeaLife Browser will offer a new dimension of context-based information integration. In this paper, we give an overview over the different components of the browser and their interplay. This SeaLife Browser will be demonstrated within three application scenarios in evidence-based medicine, literature & patent mining, and molecular biology, all relating to the study of infectious diseases. The three applications vertically integrate the molecule/cell, the tissue/organ and the patient/population level by covering the analysis of high-throughput screening data for endocytosis (the molecular entry pathway into the cell), the expression of proteins in the spatial context of tissue and organs, and a high-level library on infectious diseases designed for clinicians and their patients. For more information see http://www.biote.ctu-dresden.de/sealife.

Re-Entry: Managing Cross-Cultural Transitions.

ERIC Educational Resources Information Center

Adler, Nancy J.

1981-01-01

Studied the re-entry process of corporate and governmental employees (N=200) returning to Canada after working overseas. Research found re-entry into the original culture was a more difficult transition than moving to the foreign culture. Home-country managers tended to exhibit xenophobia in assessing the potential and actual effectiveness of…

Flavivirus infection from mosquitoes in vitro reveals cell entry at the plasma membrane

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

Vancini, Ricardo; Kramer, Laura D.; Ribeiro, Mariana

2013-01-20

Dengue and West Nile viruses are enveloped RNA viruses that belong to genus Flavivirus (family Flaviviridae) and are considered important mosquito-borne viral pathogenic agents worldwide. A potential target for intervention strategies is the virus cell entry mechanism. Previous studies of flavivirus entry have focused on the effects of biochemical and molecular inhibitors on viral entry leading to controversial conclusions suggesting that the process is dependent upon endocytosis and low pH mediated membrane fusion. In this study we analyzed the early events in the infection process by means of electron microscopy and immuno-gold labeling of viral particles during cell entry, andmore » used as a new approach for infecting cells with viruses obtained directly from mosquitoes. The results show that Dengue and West Nile viruses may infect cells by a mechanism that involves direct penetration of the host cell plasma membrane as proposed for alphaviruses.« less

Mechanism of lymphocytic choriomeningitis virus entry into cells.

PubMed

Borrow, P; Oldstone, M B

1994-01-01

The path that the arenavirus lymphocytic choriomeningitis virus (LCMV) uses to enter rodent fibroblastic cell lines was dissected by infectivity and inhibition studies and immunoelectron microscopy. Lysosomotropic weak bases (chloroquine and ammonium chloride) and carboxylic ionophores (monensin and nigericin) inhibited virus entry, assessed as virus nucleoprotein expression at early times post-infection, indicating that the entry process involved a pH-dependent fusion step in intracellular vesicles. That entry occurred in vesicles rather than by direct fusion of virions with the plasma membrane was confirmed by immunoelectron microscopy. The vesicles involved were large (150-300 nm diameter), smooth-walled, and not associated with clathrin. Unlike classical phagocytosis, virus uptake in these vesicles was a microfilament-independent process, as it was not blocked by cytochalasins. LCMV entry into rodent fibroblast cell lines thus involves viropexis in large smooth-walled vesicles, followed by a pH-dependent fusion event inside the cell.

Becoming Counselors through Growth and Learning: The Entry Transition Process

ERIC Educational Resources Information Center

Wagner, Holly H.; Hill, Nicole R.

2015-01-01

This article explored counselor development within the entry transition into counselor education programs using 4 interviews and interpretive dialogues with 8 beginning counselors. Six categories resulted from the authors' grounded theory analysis: Anticipation, Evolving Identity, Growth and Learning, Coping, Choosing to Trust the Process, and…

Metastatic infectious disease and clinical outcome in Staphylococcus aureus and Streptococcus species bacteremia.

PubMed

Vos, Fidel J; Kullberg, Bart Jan; Sturm, Patrick D; Krabbe, Paul F M; van Dijk, Arie P J; Wanten, Geert J A; Oyen, Wim J G; Bleeker-Rovers, Chantal P

2012-03-01

Early detection of metastatic infection in patients with Gram-positive bacteremia is important as morbidity and mortality are higher in the presence of these foci, probably due to incomplete eradication of clinically silent foci during initial treatment. We performed a prospective study in 115 patients with Staphylococcus aureus or Streptococcus species bacteremia with at least 1 risk factor for the development of metastatic foci, such as community acquisition, treatment delay, persistently positive blood cultures for >48 hours, and persistent fever >72 hours after initiation of treatment. An intensive search for metastatic infectious foci was performed including ¹⁸F-fluorodeoxyglucose-positron emission tomography in combination with low-dose computed tomography scanning for optimizing anatomical correlation (FDG-PET/CT) and echocardiography in the first 2 weeks of admission. Metastatic infectious foci were detected in 84 of 115 (73%) patients. Endocarditis (22 cases), endovascular infections (19 cases), pulmonary abscesses (16 cases), and spondylodiscitis (11 cases) were diagnosed most frequently. The incidence of metastatic infection was similar in patients with Streptococcus species and patients with S. aureus bacteremia. Signs and symptoms guiding the attending physician in the diagnostic workup were present in only a minority of cases (41%). An unknown portal of entry, treatment delay >48 hours, and the presence of foreign body material were significant risk factors for developing metastatic foci. Mean C-reactive protein levels on admission were significantly higher in patients with metastatic infectious foci (74 vs. 160 mg/L). FDG-PET/CT was the first technique to localize metastatic infectious foci in 35 of 115 (30%) patients. As only a minority of foci were accompanied by guiding signs or symptoms, the number of foci revealed by symptom-guided CT, ultrasound, and magnetic resonance imaging remained low. Mortality tended to be lower in patients without complicated infection compared to those with metastatic foci (16% vs. 25%, respectively). Five of 31 patients (16%) without proven metastatic foci died. In retrospect, 3 of these 5 patients likely had metastatic foci that could not be diagnosed while alive. In patients with Gram-positive bacteremia and a high risk of developing complicated infection, a structured protocol including echocardiography and FDG-PET/CT aimed at detecting metastatic infectious foci can contribute to improved outcome.

Mutagenesis Studies of the H5 Influenza Hemagglutinin Stem Loop Region*

PubMed Central

Antanasijevic, Aleksandar; Basu, Arnab; Bowlin, Terry L.; Mishra, Rama K.; Rong, Lijun; Caffrey, Michael

2014-01-01

Influenza outbreaks, particularly the pandemic 1918 H1 and avian H5 strains, are of high concern to public health. The hemagglutinin envelope protein of influenza plays a critical role in viral entry and thus is an attractive target for inhibition of virus entry. The highly conserved stem loop region of hemagglutinin has been shown to undergo critically important conformational changes during the entry process and, moreover, to be a site for inhibition of virus entry by antibodies, small proteins, and small drug-like molecules. In this work we probe the structure-function properties of the H5 hemagglutinin stem loop region by site-directed mutagenesis. We find that most mutations do not disrupt expression, proteolytic processing, incorporation into virus, or receptor binding; however, many of the mutations disrupt the entry process. We further assess the effects of mutations on inhibition of entry by a neutralizing monoclonal antibody (C179) and find examples of increased and decreased sensitivity to the antibody, consistent with the antibody binding site observed by x-ray crystallography. In addition, we tested the sensitivity of the mutants to MBX2329, a small molecule inhibitor of influenza entry. Interestingly, the mutants exhibit increased and decreased sensitivities to MBX2329, which gives further insight into the binding site of the compound on HA and potential mechanisms of escape. Finally, we have modeled the binding site of MBX2329 using molecular dynamics and find that the resulting structure is in good agreement with the mutagenesis results. Together these studies underscore the importance of the stem loop region to HA function and suggest potential sites for therapeutic intervention of influenza entry. PMID:24947513

Mutagenesis studies of the H5 influenza hemagglutinin stem loop region.

PubMed

Antanasijevic, Aleksandar; Basu, Arnab; Bowlin, Terry L; Mishra, Rama K; Rong, Lijun; Caffrey, Michael

2014-08-08

Influenza outbreaks, particularly the pandemic 1918 H1 and avian H5 strains, are of high concern to public health. The hemagglutinin envelope protein of influenza plays a critical role in viral entry and thus is an attractive target for inhibition of virus entry. The highly conserved stem loop region of hemagglutinin has been shown to undergo critically important conformational changes during the entry process and, moreover, to be a site for inhibition of virus entry by antibodies, small proteins, and small drug-like molecules. In this work we probe the structure-function properties of the H5 hemagglutinin stem loop region by site-directed mutagenesis. We find that most mutations do not disrupt expression, proteolytic processing, incorporation into virus, or receptor binding; however, many of the mutations disrupt the entry process. We further assess the effects of mutations on inhibition of entry by a neutralizing monoclonal antibody (C179) and find examples of increased and decreased sensitivity to the antibody, consistent with the antibody binding site observed by x-ray crystallography. In addition, we tested the sensitivity of the mutants to MBX2329, a small molecule inhibitor of influenza entry. Interestingly, the mutants exhibit increased and decreased sensitivities to MBX2329, which gives further insight into the binding site of the compound on HA and potential mechanisms of escape. Finally, we have modeled the binding site of MBX2329 using molecular dynamics and find that the resulting structure is in good agreement with the mutagenesis results. Together these studies underscore the importance of the stem loop region to HA function and suggest potential sites for therapeutic intervention of influenza entry. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

76 FR 13703 - New Origin Entry Separation & Containerization Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-14

... requirements for mailings and the number of pieces required per presort level will remain the same. Except as... for Periodicals piece processing based on the origin entry point. Prepare container (pallet) placards... for a reduction of sack handling and the expedited processing of individual pieces, and will result in...

Permeability Changes of Integrin-Containing Multivesicular Structures Triggered by Picornavirus Entry

PubMed Central

Soonsawad, Pan; Weerachatyanukul, Wattana; Rintanen, Nina; Espinoza, Juan; McNerney, Gregory; Marjomäki, Varpu; Cheng, R. Holland

2014-01-01

Cellular uptake of clustered α2β1-integrin induces the formation of membrane compartments that subsequently mature into a multivesicular body (MVB). Enhanced internalization mediated by clustered integrins was observed upon infection by the picornavirus echovirus 1 (EVI). We elucidated the structural features of virus-induced MVBs (vMVBs) in comparison to antibody-induced control MVBs (mock infection) by means of high-pressure cryo fixation of cells followed by immuno electron tomography during early entry of the virus. Three-dimensional tomograms revealed a marked increase in the size and complexity of these vMVBs and the intraluminal vesicles (ILVs) at 2 and 3.5 hours post infection (p.i.), in contrast to the control MVBs without virus. Breakages in the membranes of vMVBs were detected from tomograms after 2 and especially after 3.5 h suggesting that these breakages could facilitate the genome release to the cytoplasm. The in situ neutral-red labeling of viral genome showed that virus uncoating starts as early as 30 min p.i., while an increase of permeability was detected in the vMVBs between 1 and 3 hours p.i., based on a confocal microscopy assay. Altogether, the data show marked morphological changes in size and permeability of the endosomes in the infectious entry pathway of this non-enveloped enterovirus and suggest that the formed breakages facilitate the transfer of the genome to the cytoplasm for replication. PMID:25299706

Using a Scripted Data Entry Process to Transfer Legacy Immunization Data While Transitioning Between Electronic Medical Record Systems

PubMed Central

Michel, J.; Hsiao, A.; Fenick, A.

2014-01-01

Summary Background Transitioning between Electronic Medical Records (EMR) can result in patient data being stranded in legacy systems with subsequent failure to provide appropriate patient care. Manual chart abstraction is labor intensive, error-prone, and difficult to institute for immunizations on a systems level in a timely fashion. Objectives We sought to transfer immunization data from two of our health system’s soon to be replaced EMRs to the future EMR using a single process instead of separate interfaces for each facility. Methods We used scripted data entry, a process where a computer automates manual data entry, to insert data into the future EMR. Using the Center for Disease Control’s CVX immunization codes we developed a bridge between immunization identifiers within our system’s EMRs. We performed a two-step process evaluation of the data transfer using automated data comparison and manual chart review. Results We completed the data migration from two facilities in 16.8 hours with no data loss or corruption. We successfully populated the future EMR with 99.16% of our legacy immunization data – 500,906 records – just prior to our EMR transition date. A subset of immunizations, first recognized during clinical care, had not originally been extracted from the legacy systems. Once identified, this data – 1,695 records – was migrated using the same process with minimal additional effort. Conclusions Scripted data entry for immunizations is more accurate than published estimates for manual data entry and we completed our data transfer in 1.2% of the total time we predicted for manual data entry. Performing this process before EMR conversion helped identify obstacles to data migration. Drawing upon this work, we will reuse this process for other healthcare facilities in our health system as they transition to the future EMR. PMID:24734139

Emerging arboviruses and public health challenges in Brazil

PubMed Central

Lima-Camara, Tamara Nunes

2016-01-01

ABSTRACT Environmental modification by anthropogenic actions, disordered urban growth, globalization of international exchange and climate change are some factors that help the emergence and dissemination of human infectious diseases transmitted by vectors. This review discusses the recent entry of three arboviruses in Brazil: Chikungunya, West Nile, and Zika virus, focusing on the challenges for the Country’s public health. The Brazilian population is exposed to infections caused by these three arboviruses widely distributed on the national territory and associated with humans. Without effective vaccine and specific treatment, the maintainance and integration of a continuos entomological and epidemiological surveillance are important so we can set methods to control and prevent these arboviruses in the Country. PMID:27355468

Infections in cancer patients on a protected environment-prophylactic antibiotic program.

PubMed

Bodey, G P; Rodriguez, V

1975-10-01

A total of 102 studies were conducted on 89 patients receiving cancer chemotherapy while on a protected environment-prophylactic antibiotic program. Major infections occurred during 22 studies. The majority of both minor and major infections originated during the first five weeks after the patients entered the protected environment units. The frequency of infectious complications was inversely related to the circulating neutrophil count. The majority of infections were cases of cellulitis, pharyngitis, pneumonia and septicemia. Most of the infections were caused by gram-negative bacilli. The majority of organisms causing infection had persisted in the patients after their entry into the protected environment units despite the use of prophylactic antibiotics.

NTCP and Beyond: Opening the Door to Unveil Hepatitis B Virus Entry

PubMed Central

Watashi, Koichi; Urban, Stephan; Li, Wenhui; Wakita, Takaji

2014-01-01

Chronic hepatitis B virus (HBV) infection, affecting approximately 240 million people worldwide, is a major public health problem that elevates the risk of developing liver cirrhosis and hepatocellular carcinoma. Given that current anti-HBV drugs are limited to interferon-based regimens and nucleos(t)ide analogs, the development of new anti-HBV agents is urgently needed. The viral entry process is generally an attractive target implicated in antiviral strategies. Using primary cells from humans and Tupaia belangeri, as well as HepaRG cells, important determinants of viral entry have been achieved. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was identified as an HBV entry receptor and enabled the establishment of a susceptible cell line that can efficiently support HBV infection. This finding will allow a deeper understanding of the requirements for efficient HBV infection, including the elucidation of the molecular entry mechanism. In addition, pharmacological studies suggest that NTCP is able to serve as a therapeutic target. This article summarizes our current knowledge on the mechanisms of HBV entry and the role of NTCP in this process. PMID:24557582

NTCP and beyond: opening the door to unveil hepatitis B virus entry.

PubMed

Watashi, Koichi; Urban, Stephan; Li, Wenhui; Wakita, Takaji

2014-02-19

Chronic hepatitis B virus (HBV) infection, affecting approximately 240 million people worldwide, is a major public health problem that elevates the risk of developing liver cirrhosis and hepatocellular carcinoma. Given that current anti-HBV drugs are limited to interferon-based regimens and nucleos(t)ide analogs, the development of new anti-HBV agents is urgently needed. The viral entry process is generally an attractive target implicated in antiviral strategies. Using primary cells from humans and Tupaia belangeri, as well as HepaRG cells, important determinants of viral entry have been achieved. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was identified as an HBV entry receptor and enabled the establishment of a susceptible cell line that can efficiently support HBV infection. This finding will allow a deeper understanding of the requirements for efficient HBV infection, including the elucidation of the molecular entry mechanism. In addition, pharmacological studies suggest that NTCP is able to serve as a therapeutic target. This article summarizes our current knowledge on the mechanisms of HBV entry and the role of NTCP in this process.

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

Bose, Sayantan, E-mail: sayantan_bose@hms.harvard.edu; Jardetzky, Theodore S.; Lamb, Robert A., E-mail: ralamb@northwestern.edu

The Paramyxoviridae include some of the great and ubiquitous disease-causing viruses of humans and animals. In most paramyxoviruses, two viral membrane glycoproteins, fusion protein (F) and receptor binding protein (HN, H or G) mediate a concerted process of recognition of host cell surface molecules followed by fusion of viral and cellular membranes, resulting in viral nucleocapsid entry into the cytoplasm. The interactions between the F and HN, H or G viral glycoproteins and host molecules are critical in determining host range, virulence and spread of these viruses. Recently, atomic structures, together with biochemical and biophysical studies, have provided major insightsmore » into how these two viral glycoproteins successfully interact with host receptors on cellular membranes and initiate the membrane fusion process to gain entry into cells. These studies highlight the conserved core mechanisms of paramyxovirus entry that provide the fundamental basis for rational anti-viral drug design and vaccine development. - Highlights: • New structural and functional insights into paramyxovirus entry mechanisms. • Current data on paramyxovirus glycoproteins suggest a core conserved entry mechanism. • Diverse mechanisms preventing premature fusion activation exist in these viruses. • Precise spacio-temporal interplay between paramyxovirus glycoproteins initiate entry.« less

Meteor Entry and Breakup Based on Evolution of NASAs Entry Capsule Design Tools

NASA Technical Reports Server (NTRS)

Prabku, Dinesh K.; Saunders, D.; Stern, E.; Chen, Y.-K.; Allen, G.; Agrawal, P.; Jaffe, R.; White, S.; Tauber, M.; Bauschlicher, C.;

Single-Particle Detection of Transcription following Rotavirus Entry

PubMed Central

Salgado, Eric N.; Upadhyayula, Srigokul

2017-01-01

ABSTRACT Infectious rotavirus particles are triple-layered, icosahedral assemblies. The outer layer proteins, VP4 (cleaved to VP8* and VP5*) and VP7, surround a transcriptionally competent, double-layer particle (DLP), which they deliver into the cytosol. During entry of rhesus rotavirus, VP8* interacts with cell surface gangliosides, allowing engulfment into a membrane vesicle by a clathrin-independent process. Escape into the cytosol and outer-layer shedding depend on interaction of a hydrophobic surface on VP5* with the membrane bilayer and on a large-scale conformational change. We report here experiments that detect the fate of released DLPs and their efficiency in initiating RNA synthesis. By replacing the outer layer with fluorescently tagged, recombinant proteins and also tagging the DLP, we distinguished particles that have lost their outer layer and entered the cytosol (uncoated) from those still within membrane vesicles. We used fluorescent in situ hybridization with probes for nascent transcripts to determine how soon after uncoating transcription began and what fraction of the uncoated particles were active in initiating RNA synthesis. We detected RNA synthesis by uncoated particles as early as 15 min after adding virus. The uncoating efficiency was 20 to 50%; of the uncoated particles, about 10 to 15% synthesized detectable RNA. In the format of our experiments, about 10% of the added particles attached to the cell surface, giving an overall ratio of added particles to RNA-synthesizing particles of between 250:1 and 500:1, in good agreement with the ratio of particles to focus-forming units determined by infectivity assays. Thus, RNA synthesis by even a single, uncoated particle can initiate infection in a cell. IMPORTANCE The pathways by which a virus enters a cell transform its packaged genome into an active one. Contemporary fluorescence microscopy can detect individual virus particles as they enter cells, allowing us to map their multistep entry pathways. Rotaviruses, like most viruses that lack membranes of their own, disrupt or perforate the intracellular, membrane-enclosed compartment into which they become engulfed following attachment to a cell surface, in order to gain access to the cell interior. The properties of rotavirus particles make it possible to determine molecular mechanisms for these entry steps. In the work described here, we have asked the following question: what fraction of the rotavirus particles that penetrate into the cell make new viral RNA? We find that of the cell-attached particles, between 20 and 50% ultimately penetrate, and of these, about 10% make RNA. RNA synthesis by even a single virus particle can initiate a productive infection. PMID:28701394

Circulating microRNAs as Potential Biomarkers of Infectious Disease

PubMed Central

Correia, Carolina N.; Nalpas, Nicolas C.; McLoughlin, Kirsten E.; Browne, John A.; Gordon, Stephen V.; MacHugh, David E.; Shaughnessy, Ronan G.

2017-01-01

microRNAs (miRNAs) are a class of small non-coding endogenous RNA molecules that regulate a wide range of biological processes by post-transcriptionally regulating gene expression. Thousands of these molecules have been discovered to date, and multiple miRNAs have been shown to coordinately fine-tune cellular processes key to organismal development, homeostasis, neurobiology, immunobiology, and control of infection. The fundamental regulatory role of miRNAs in a variety of biological processes suggests that differential expression of these transcripts may be exploited as a novel source of molecular biomarkers for many different disease pathologies or abnormalities. This has been emphasized by the recent discovery of remarkably stable miRNAs in mammalian biofluids, which may originate from intracellular processes elsewhere in the body. The potential of circulating miRNAs as biomarkers of disease has mainly been demonstrated for various types of cancer. More recently, however, attention has focused on the use of circulating miRNAs as diagnostic/prognostic biomarkers of infectious disease; for example, human tuberculosis caused by infection with Mycobacterium tuberculosis, sepsis caused by multiple infectious agents, and viral hepatitis. Here, we review these developments and discuss prospects and challenges for translating circulating miRNA into novel diagnostics for infectious disease. PMID:28261201

An approach to and web-based tool for infectious disease outbreak intervention analysis

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

Daughton, Ashlynn R.; Generous, Nicholas; Priedhorsky, Reid

Infectious diseases are a leading cause of death globally. Decisions surrounding how to control an infectious disease outbreak currently rely on a subjective process involving surveillance and expert opinion. However, there are many situations where neither may be available. Modeling can fill gaps in the decision making process by using available data to provide quantitative estimates of outbreak trajectories. Effective reduction of the spread of infectious diseases can be achieved through collaboration between the modeling community and public health policy community. However, such collaboration is rare, resulting in a lack of models that meet the needs of the public healthmore » community. Here we show a Susceptible-Infectious-Recovered (SIR) model modified to include control measures that allows parameter ranges, rather than parameter point estimates, and includes a web user interface for broad adoption. We apply the model to three diseases, measles, norovirus and influenza, to show the feasibility of its use and describe a research agenda to further promote interactions between decision makers and the modeling community.« less

An approach to and web-based tool for infectious disease outbreak intervention analysis

DOE PAGES

Daughton, Ashlynn R.; Generous, Nicholas; Priedhorsky, Reid; ...

2017-04-18

Infectious diseases are a leading cause of death globally. Decisions surrounding how to control an infectious disease outbreak currently rely on a subjective process involving surveillance and expert opinion. However, there are many situations where neither may be available. Modeling can fill gaps in the decision making process by using available data to provide quantitative estimates of outbreak trajectories. Effective reduction of the spread of infectious diseases can be achieved through collaboration between the modeling community and public health policy community. However, such collaboration is rare, resulting in a lack of models that meet the needs of the public healthmore » community. Here we show a Susceptible-Infectious-Recovered (SIR) model modified to include control measures that allows parameter ranges, rather than parameter point estimates, and includes a web user interface for broad adoption. We apply the model to three diseases, measles, norovirus and influenza, to show the feasibility of its use and describe a research agenda to further promote interactions between decision makers and the modeling community.« less

The Large Marseillevirus Explores Different Entry Pathways by Forming Giant Infectious Vesicles.

PubMed

Arantes, Thalita Souza; Rodrigues, Rodrigo Araújo Lima; Dos Santos Silva, Ludmila Karen; Oliveira, Graziele Pereira; de Souza, Helton Luís; Khalil, Jacques Y B; de Oliveira, Danilo Bretas; Torres, Alice Abreu; da Silva, Luis Lamberti; Colson, Philippe; Kroon, Erna Geessien; da Fonseca, Flávio Guimarães; Bonjardim, Cláudio Antônio; La Scola, Bernard; Abrahão, Jônatas Santos

2016-06-01

Triggering the amoebal phagocytosis process is a sine qua non condition for most giant viruses to initiate their replication cycle and consequently to promote their progeny formation. It is well known that the amoebal phagocytosis process requires the recognition of particles of >500 nm, and most amoebal giant viruses meet this requirement, such as mimivirus, pandoravirus, pithovirus, and mollivirus. However, in the context of the discovery of amoebal giant viruses in the last decade, Marseillevirus marseillevirus (MsV) has drawn our attention, because despite its ability to successfully replicate in Acanthamoeba, remarkably it does not fulfill the >500-nm condition, since it presents an ∼250-nm icosahedrally shaped capsid. We deeply investigated the MsV cycle by using a set of methods, including virological, molecular, and microscopic (immunofluorescence, scanning electron microscopy, and transmission electron microscopy) assays. Our results revealed that MsV is able to form giant vesicles containing dozens to thousands of viral particles wrapped by membranes derived from amoebal endoplasmic reticulum. Remarkably, our results strongly suggested that these giant vesicles are able to stimulate amoebal phagocytosis and to trigger the MsV replication cycle by an acidification-independent process. Also, we observed that MsV entry may occur by the phagocytosis of grouped particles (without surrounding membranes) and by an endosome-stimulated pathway triggered by single particles. Taken together, not only do our data deeply describe the main features of MsV replication cycle, but this is the first time, to our knowledge, that the formation of giant infective vesicles related to a DNA virus has been described. Triggering the amoebal phagocytosis process is a sine qua non condition required by most giant viruses to initiate their replication cycle. This process requires the recognition of particles of >500 nm, and many giant viruses meet this requirement. However, MsV is unusual, as despite having particles of ∼250 nm it is able to replicate in Acanthamoeba Our results revealed that MsV is able to form giant vesicles, containing dozens to thousands of viral particles, wrapped in membranes derived from amoebal endoplasmic reticulum. Remarkably, our results strongly suggest that these giant vesicles are able to stimulate phagocytosis using an acidification-independent process. Our work not only describes the main features of the MsV replication cycle but also describes, for the first time to our knowledge, the formation of huge infective vesicles in a large DNA viruses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Translocation of an 89-kDa periplasmic protein is associated with Holospora infection

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

Iwatani, Koichi; Dohra, Hideo; Lang, B. Franz

2005-12-02

The symbiotic bacterium Holospora obtusa infects the macronucleus of the ciliate Paramecium caudatum. After ingestion by its host, an infectious form of Holospora with an electron-translucent tip passes through the host digestive vacuole and penetrates the macronuclear envelope with this tip. To investigate the underlying molecular mechanism of this process, we raised a monoclonal antibody against the tip-specific 89-kDa protein, sequenced this partially, and identified the corresponding complete gene. The deduced protein sequence carries two actin-binding motifs. Indirect immunofluorescence microscopy shows that during escape from the host digestive vacuole, the 89-kDa proteins translocates from the inside to the outside ofmore » the tip. When the bacterium invades the macronucleus, the 89-kDa protein is left behind at the entry point of the nuclear envelope. Transmission electron microscopy shows the formation of fine fibrous structures that co-localize with the antibody-labeled regions of the bacterium. Our findings suggest that the 89-kDa protein plays a role in Holospora's escape from the host digestive vacuole, the migration through the host cytoplasm, and the invasion into the macronucleus.« less

Man Versus Machine: Comparing Double Data Entry and Optical Mark Recognition for Processing CAHPS Survey Data.

PubMed

Fifolt, Matthew; Blackburn, Justin; Rhodes, David J; Gillespie, Shemeka; Bennett, Aleena; Wolff, Paul; Rucks, Andrew

Historically, double data entry (DDE) has been considered the criterion standard for minimizing data entry errors. However, previous studies considered data entry alternatives through the limited lens of data accuracy. This study supplies information regarding data accuracy, operational efficiency, and cost for DDE and Optical Mark Recognition (OMR) for processing the Consumer Assessment of Healthcare Providers and Systems 5.0 survey. To assess data accuracy, we compared error rates for DDE and OMR by dividing the number of surveys that were arbitrated by the total number of surveys processed for each method. To assess operational efficiency, we tallied the cost of data entry for DDE and OMR after survey receipt. Costs were calculated on the basis of personnel, depreciation for capital equipment, and costs of noncapital equipment. The cost savings attributed to this method were negated by the operational efficiency of OMR. There was a statistical significance between rates of arbitration between DDE and OMR; however, this statistical significance did not create a practical significance. The potential benefits of DDE in terms of data accuracy did not outweigh the operational efficiency and thereby financial savings of OMR.

Orbiter Entry Aerothermodynamics Practical Engineering and Applied Research

NASA Technical Reports Server (NTRS)

Campbell, Charles H.

2009-01-01

The contents include: 1) Organization of the Orbiter Entry Aeroheating Working Group; 2) Overview of the Principal RTF Aeroheating Tools Utilized for Tile Damage Assessment; 3) Description of the Integrated Tile Damage Assessment Team Analyses Process; 4) Space Shuttle Flight Support Process; and 5) JSC Applied Aerosciences and CFD Branch Applied Research Interests.

Integrated Design System (IDS) Tools for the Spacecraft Aeroassist/Entry Vehicle Design Process

NASA Technical Reports Server (NTRS)

Olynick, David; Braun, Robert; Langhoff, Steven R. (Technical Monitor)

1997-01-01

The definition of the Integrated Design System technology focus area as presented in the NASA Information Technology center of excellence strategic plan is described. The need for IDS tools in the aeroassist/entry vehicle design process is illustrated. Initial and future plans for spacecraft IDS tool development are discussed.

Amotivation and Indecision in the Decision-Making Processes Associated with University Entry

ERIC Educational Resources Information Center

Jung, Jae Yup

2013-01-01

This study developed and tested two models that examined the decision-making processes of adolescents relating to entry into university, in terms of the extent to which they may be amotivated and undecided. The models incorporated variables derived from self-determination theory, expectancy-value theory, and research on occupational indecision. A…

Mechanisms of Virus-Induced Neural Cell Death

DTIC Science & Technology

2005-03-01

Y, et al. Brief CMV, with isolates being resistant to acy- report: severe infectious mononucleosis -like clovir, famciclovir, and valacyclovir, and...protease depen- by 24 h post-infection. The completion of the one-step dent process. Conversion to infectious subvirion particles growth curve precedes...apoptosis increases progres- cell attachment protein o-1 (56). sively at 24-48 h post-infection (92). ISVPs are infectious and can be formed either intra

Optimal evaluation of infectious medical waste disposal companies using the fuzzy analytic hierarchy process

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

Ho, Chao Chung, E-mail: ho919@pchome.com.tw

Ever since Taiwan's National Health Insurance implemented the diagnosis-related groups payment system in January 2010, hospital income has declined. Therefore, to meet their medical waste disposal needs, hospitals seek suppliers that provide high-quality services at a low cost. The enactment of the Waste Disposal Act in 1974 had facilitated some improvement in the management of waste disposal. However, since the implementation of the National Health Insurance program, the amount of medical waste from disposable medical products has been increasing. Further, of all the hazardous waste types, the amount of infectious medical waste has increased at the fastest rate. This ismore » because of the increase in the number of items considered as infectious waste by the Environmental Protection Administration. The present study used two important findings from previous studies to determine the critical evaluation criteria for selecting infectious medical waste disposal firms. It employed the fuzzy analytic hierarchy process to set the objective weights of the evaluation criteria and select the optimal infectious medical waste disposal firm through calculation and sorting. The aim was to propose a method of evaluation with which medical and health care institutions could objectively and systematically choose appropriate infectious medical waste disposal firms.« less

Optimal evaluation of infectious medical waste disposal companies using the fuzzy analytic hierarchy process.

PubMed

Ho, Chao Chung

2011-07-01

Ever since Taiwan's National Health Insurance implemented the diagnosis-related groups payment system in January 2010, hospital income has declined. Therefore, to meet their medical waste disposal needs, hospitals seek suppliers that provide high-quality services at a low cost. The enactment of the Waste Disposal Act in 1974 had facilitated some improvement in the management of waste disposal. However, since the implementation of the National Health Insurance program, the amount of medical waste from disposable medical products has been increasing. Further, of all the hazardous waste types, the amount of infectious medical waste has increased at the fastest rate. This is because of the increase in the number of items considered as infectious waste by the Environmental Protection Administration. The present study used two important findings from previous studies to determine the critical evaluation criteria for selecting infectious medical waste disposal firms. It employed the fuzzy analytic hierarchy process to set the objective weights of the evaluation criteria and select the optimal infectious medical waste disposal firm through calculation and sorting. The aim was to propose a method of evaluation with which medical and health care institutions could objectively and systematically choose appropriate infectious medical waste disposal firms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Resistance and Protective Immunity in Redfish Lake Sockeye Salmon Exposed to M Type Infectious Hematopoietic Necrosis Virus (IHNV)

USGS Publications Warehouse

Kurath, Gael; Garver, Kyle; Purcell, Maureen K.; LaPatra, Scott E.

2010-01-01

Differential virulence of infectious hematopoietic necrosis virus (IHNV) isolates from the U and M phylogenetic subgroups is clearly evident in the Redfish Lake (RFL) strain of sockeye salmon Oncorhynchus nerka. In these fish, experimental immersion challenges with U isolates cause extremely high mortality and M isolates cause low or no mortality. When survivors of M virus immersion challenges were exposed to a secondary challenge with virulent U type virus they experienced high mortality, indicating that the primary M challenge did not elicit protective immunity. Delivery of a moderate dose (2 × 104 plaque-forming units [PFU]/fish) of virus by intraperitoneal injection challenge did not overcome RFL sockeye salmon resistance to M type IHNV. Injection challenge with a high dose (5 × 106 PFU/fish) of M type virus caused 10% mortality, and in this case survivors did develop protective immunity against a secondary U type virus challenge. Thus, although it is possible for M type IHNV to elicit cross-protective immunity in this disease model, it does not develop after immersion challenge despite entry, transient replication of M virus to low levels, stimulation of innate immune genes, and development of neutralizing antibodies in some fish.

The zebrafish galectins Drgal1-L2 and Drgal3-L1 bind in vitro to the infectious hematopoietic necrosis virus (IHNV) glycoprotein and reduce viral adhesion to fish epithelial cells*

PubMed Central

Feng, Chiguang; González-Montalbán, Núria; Ravindran, Chinnarajan; Jackson, Shawn; de las Heras-Sánchez, Ana; Giomarelli, Barbara; Ahmed, Hafiz; Haslam, Stuart M.; Wu, Gang; Dell, Anne; Ammayappan, Arun; Vakharia, Vikram N.; Vasta, Gerardo R.

2015-01-01

The infectious hematopoietic necrosis virus (IHNV; Rhabdoviridae, Novirhabdovirus) infects teleost fish, such as salmon and trout, and is responsible for significant losses in the aquaculture industry and in wild fish populations. Although IHNV enters the host through the skin at the base of the fins, the viral adhesion and entry mechanisms are not fully understood. In recent years, evidence has accumulated in support of the key roles played by protein-carbohydrate interactions between host lectins secreted to the extracellular space and virion envelope glycoproteins in modulating viral adhesion and infectivity. In this study, we assessed in vitro the potential role(s) of zebrafish (Danio rerio) proto type galectin-1 (Drgal1-L2) and a chimera galectin-3 (Drgal3-L1) in IHNV adhesion to epithelial cells. Our results suggest that the extracellular Drgal1-L2 and Drgal3-L1 interact directly and in a carbohydrate-dependent manner with the IHNV glycosylated envelope and glycans on the epithelial cell surface, significantly reducing viral adhesion. PMID:26429411

Pediatric epstein-barr virus carriers with or without tonsillar enlargement may substantially contribute to spreading of the virus.

PubMed

Hug, Martina; Dorner, Marcus; Fröhlich, Franziska Zucol; Gysin, Claudine; Neuhaus, Diego; Nadal, David; Berger, Christoph

2010-10-15

Human-to-human transmission of the persistent infection establishing Epstein-Barr virus (EBV) occurs via saliva. Tonsils act as important portal of entry and exit of EBV. The contagiousness of pediatric EBV carriers and the role played by tonsillar enlargement (TE) are not known. We compared EBV shedding in mouthwash samples from pediatric EBV carriers with or without TE to that in mouthwash samples from pediatric patients with infectious mononucleosis (IM), the symptomatic form of primary infection if delayed after the age of 5 years. EBV DNA was quantified by polymerase chain reaction, and contagiousness was assessed using the cord lymphocyte transformation assay. EBV carriers with TE shed EBV DNA at an almost similar frequency (although in lower amounts) as pediatric patients with acute IM but more frequently (P <.001) and in higher amounts (P = .038) than EBV carriers without TE. EBV DNA levels in mouthwash samples from EBV carriers with TE mirrored levels in tonsils and gradually declined after tonsillectomy. Almost half of the mouthwash samples from pediatric EBV carriers contained infectious EBV. Pediatric EBV carriers--in particular, those with TE-may considerably contribute to the spreading of EBV in industrialized countries.

The Apollo Structured Vocabulary: an OWL2 ontology of phenomena in infectious disease epidemiology and population biology for use in epidemic simulation.

PubMed

Hogan, William R; Wagner, Michael M; Brochhausen, Mathias; Levander, John; Brown, Shawn T; Millett, Nicholas; DePasse, Jay; Hanna, Josh

2016-08-18

We developed the Apollo Structured Vocabulary (Apollo-SV)-an OWL2 ontology of phenomena in infectious disease epidemiology and population biology-as part of a project whose goal is to increase the use of epidemic simulators in public health practice. Apollo-SV defines a terminology for use in simulator configuration. Apollo-SV is the product of an ontological analysis of the domain of infectious disease epidemiology, with particular attention to the inputs and outputs of nine simulators. Apollo-SV contains 802 classes for representing the inputs and outputs of simulators, of which approximately half are new and half are imported from existing ontologies. The most important Apollo-SV class for users of simulators is infectious disease scenario, which is a representation of an ecosystem at simulator time zero that has at least one infection process (a class) affecting at least one population (also a class). Other important classes represent ecosystem elements (e.g., households), ecosystem processes (e.g., infection acquisition and infectious disease), censuses of ecosystem elements (e.g., censuses of populations), and infectious disease control measures. In the larger project, which created an end-user application that can send the same infectious disease scenario to multiple simulators, Apollo-SV serves as the controlled terminology and strongly influences the design of the message syntax used to represent an infectious disease scenario. As we added simulators for different pathogens (e.g., malaria and dengue), the core classes of Apollo-SV have remained stable, suggesting that our conceptualization of the information required by simulators is sound. Despite adhering to the OBO Foundry principle of orthogonality, we could not reuse Infectious Disease Ontology classes as the basis for infectious disease scenarios. We thus defined new classes in Apollo-SV for host, pathogen, infection, infectious disease, colonization, and infection acquisition. Unlike IDO, our ontological analysis extended to existing mathematical models of key biological phenomena studied by infectious disease epidemiology and population biology. Our ontological analysis as expressed in Apollo-SV was instrumental in developing a simulator-independent representation of infectious disease scenarios that can be run on multiple epidemic simulators. Our experience suggests the importance of extending ontological analysis of a domain to include existing mathematical models of the phenomena studied by the domain. Apollo-SV is freely available at: http://purl.obolibrary.org/obo/apollo_sv.owl .

78 FR 69434 - Post-Summary Corrections to Entry Summaries Filed in ACE Pursuant to the ESAR IV Test...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-19

...'s) Entry Summary, Accounts and Revenue (ESAR IV) test program concerning the processing of post... DEPARTMENT OF HOMELAND SECURITY U.S. Customs and Border Protection Post-Summary Corrections to Entry Summaries Filed in ACE Pursuant to the ESAR IV Test: Modifications and Clarifications AGENCY: U.S...

49 CFR 611.7 - Relation to planning and project development processes.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Preliminary Engineering. Consistent with 49 USC 5309(e)(6) and 5328(a)(2), FTA will approve/disapprove entry... rating of “recommended” to be approved for entry into preliminary engineering. (4) This part does not in... 5328(a)(3), FTA will approve/disapprove entry of a proposed project into final design within 120 days...

From Higher Education to Work Patterns of Labor Market Entry in Germany and the US

ERIC Educational Resources Information Center

Jacob, Marita; Weiss, Felix

2010-01-01

Comparative studies describing the transition from higher education to work have often simplified the complex transition processes involved. In this paper we extend previous research by taking into account several steps that comprise labor market entry, e.g., recurrent education leading to more than one instance of labor market entry. By comparing…

Return on Investment Point of Service Computerized Provider Charge Entry

PubMed Central

Kiepek, Wendy; FitzHenry, Fern; Shultz, Edward K

2003-01-01

Provider charge entry systems offer many benefits to users and organizations. At Vanderbilt University Medical Center, a web-based provider charge entry system promises to deliver benefits in reducing days in accounts receivable, reducing labor required for claims and edit processing, and implementing business rules that deliver both strategic and financial benefits. PMID:14728396

Online Adaptation for Mobile Device Text Input Personalization

ERIC Educational Resources Information Center

Baldwin, Tyler

2012-01-01

As mobile devices have become more common, the need for efficient methods of mobile device text entry has grown. With this growth comes new challenges, as the constraints imposed by the size, processing power, and design of mobile devices impairs traditional text entry mechanisms in ways not seen in previous text entry tasks. To combat this,…

Lymph nodes fine needle cytology in the diagnosis of infectious diseases: clinical settings.

PubMed

Natella, Valentina; Cozzolino, Immacolata; Sosa Fernandez, Laura Virginia; Vigliar, Elena

2012-01-01

Lymph node reactive hyperplasia, caused by specific infectious etiologic factors, represents the most frequent cause of enlarged peripheral lymph nodes. The main infectious agents are viruses, pyogenic bacteria, mycobacteria, fungi and protozoa that may determine unspecific or specific pathological entities, such as cat-scratch disease, toxoplasmosis or infectious mononucleosis. Lymph node fine needle cytology (FNC) is a safe, simple, cost-effective and efficient technique that quickly provides information about the cell population and the nature of the process. FNC can also provide suitable material for ancillary techniques, such as flow cytometry, immunocytochemistry, molecular biology and microbiological examinations. This study focuses on the cytological features of benign lymphadenopathy of infectious origin and their possible contribution to the clinical setting definition of corresponding patients.

Identifying climate drivers of infectious disease dynamics: recent advances and challenges ahead

PubMed Central

Walter, Katharine S.; Wesolowski, Amy; Buckee, Caroline O.; Shevliakova, Elena; Tatem, Andrew J.; Boos, William R.; Weinberger, Daniel M.; Pitzer, Virginia E.

2017-01-01

Climate change is likely to profoundly modulate the burden of infectious diseases. However, attributing health impacts to a changing climate requires being able to associate changes in infectious disease incidence with the potentially complex influences of climate. This aim is further complicated by nonlinear feedbacks inherent in the dynamics of many infections, driven by the processes of immunity and transmission. Here, we detail the mechanisms by which climate drivers can shape infectious disease incidence, from direct effects on vector life history to indirect effects on human susceptibility, and detail the scope of variation available with which to probe these mechanisms. We review approaches used to evaluate and quantify associations between climate and infectious disease incidence, discuss the array of data available to tackle this question, and detail remaining challenges in understanding the implications of climate change for infectious disease incidence. We point to areas where synthesis between approaches used in climate science and infectious disease biology provide potential for progress. PMID:28814655

Identifying climate drivers of infectious disease dynamics: recent advances and challenges ahead.

PubMed

Metcalf, C Jessica E; Walter, Katharine S; Wesolowski, Amy; Buckee, Caroline O; Shevliakova, Elena; Tatem, Andrew J; Boos, William R; Weinberger, Daniel M; Pitzer, Virginia E

2017-08-16

Climate change is likely to profoundly modulate the burden of infectious diseases. However, attributing health impacts to a changing climate requires being able to associate changes in infectious disease incidence with the potentially complex influences of climate. This aim is further complicated by nonlinear feedbacks inherent in the dynamics of many infections, driven by the processes of immunity and transmission. Here, we detail the mechanisms by which climate drivers can shape infectious disease incidence, from direct effects on vector life history to indirect effects on human susceptibility, and detail the scope of variation available with which to probe these mechanisms. We review approaches used to evaluate and quantify associations between climate and infectious disease incidence, discuss the array of data available to tackle this question, and detail remaining challenges in understanding the implications of climate change for infectious disease incidence. We point to areas where synthesis between approaches used in climate science and infectious disease biology provide potential for progress. © 2017 The Authors.

Auditing an Online Self-reported Interventional Radiology Adverse Event Database for Compliance and Accuracy.

PubMed

Burch, Ezra A; Shyn, Paul B; Chick, Jeffrey F; Chauhan, Nikunj R

2017-04-01

The purpose of this study was to determine whether auditing an online self-reported interventional radiology quality assurance database improves compliance with record entry or improves the accuracy of adverse event (AE) reporting and grading. Physicians were trained in using the database before the study began. An audit of all database entries for the first 3 months, or the first quarter, was performed, at which point physicians were informed of the audit process; entries for the subsequent 3 months, or the second quarter, were again audited. Results between quarters were compared. Compliance with record entry improved from the first to second quarter, but reminders were necessary to ensure 100% compliance with record entry. Knowledge of the audit process did not significantly improve self-reporting of AE or accuracy of AE grading. However, auditing significantly changed the final AE reporting rates and grades. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Immunosuppression-Induced Susceptibility of Inbred Hamsters (Mesocricetus auratus) to Lethal-Disease by Lymphocytic Choriomeningitis Virus Infection

DTIC Science & Technology

1987-01-01

Genovesi* and C. J. Peters L..’ Army Medical Research Institute in Infectious Diseases. -- f) Department of Viral Pathogenesis and Inmunology. Disease...implied that immunopathogenetic mechanisms underlie the clinical outcome of these infections [1.7.8. 15. 23, 29]. By this process. infectious - virus...elimination by an anti-viral immune response would occur with dispase and death- the absence of this immune response should favor ), infectious -virus

Adolescent Decision-Making Processes regarding University Entry: A Model Incorporating Cultural Orientation, Motivation and Occupational Variables

ERIC Educational Resources Information Center

Jung, Jae Yup

2013-01-01

This study tested a newly developed model of the cognitive decision-making processes of senior high school students related to university entry. The model incorporated variables derived from motivation theory (i.e. expectancy-value theory and the theory of reasoned action), literature on cultural orientation and occupational considerations. A…

The use of failure mode and effects analysis to construct an effective disposal and prevention mechanism for infectious hospital waste

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

Ho, Chao Chung, E-mail: ho919@pchome.com.tw; Liao, Ching-Jong

Highlights: > This study is based on a real case in a regional teaching hospital in Taiwan. > We use Failure mode and effects analysis (FMEA) as the evaluation method. > We successfully identify the risk factors of infectious waste disposal. > We propose plans for the detection of exceptional cases of infectious waste. - Abstract: In recent times, the quality of medical care has been continuously improving in medical institutions wherein patient-centred care has been emphasized. Failure mode and effects analysis (FMEA) has also been promoted as a method of basic risk management and as part of total qualitymore » management (TQM) for improving the quality of medical care and preventing mistakes. Therefore, a study was conducted using FMEA to evaluate the potential risk causes in the process of infectious medical waste disposal, devise standard procedures concerning the waste, and propose feasible plans for facilitating the detection of exceptional cases of infectious waste. The analysis revealed the following results regarding medical institutions: (a) FMEA can be used to identify the risk factors of infectious waste disposal. (b) During the infectious waste disposal process, six items were scored over 100 in the assessment of uncontrolled risks: erroneous discarding of infectious waste by patients and their families, erroneous discarding by nursing staff, erroneous discarding by medical staff, cleaning drivers pierced by sharp articles, cleaning staff pierced by sharp articles, and unmarked output units. Therefore, the study concluded that it was necessary to (1) provide education and training about waste classification to the medical staff, patients and their families, nursing staff, and cleaning staff; (2) clarify the signs of caution; and (3) evaluate the failure mode and strengthen the effects.« less

Removal of virus from boar semen spiked with porcine circovirus type 2.

PubMed

Blomqvist, Gunilla; Persson, Maria; Wallgren, Margareta; Wallgren, Per; Morrell, Jane M

2011-06-01

The virus porcine circovirus type 2 (PCV2) is associated with different disease entities, including reproductive failure. The objective of this study was to investigate the use of a semen processing technique for the elimination of infectious PCV2 in semen. PCV2 was chosen as a model virus because of its small size, high resistance to inactivation and as a known risk factor for boar semen contamination. Aliquots of ejaculates were spiked with PCV2 and processed by a double processing technique, consisting of Single Layer Centrifugation on Androcoll™-P followed by a "swim-up" procedure. Samples were collected from the resulting fractions during the selection process and analyzed for the presence of infectious PCV2. Virus titres were determined by performing a 50% tissue culture infective dose assay (TCID(50)) by end point dilution and with the use of an indirect peroxidise monolayer assay technique. With an initial infectious virus titre of 3.25-3.82 (TCID(50))/50μL the two-step sperm selection method eliminated 2.92±0.23 logs of infectious PCV2, corresponding to more than 99% reduction. Sperm quality was not affected by the selection procedure. Copyright © 2011 Elsevier B.V. All rights reserved.

Deburring: an annotated bibliography. Volume V

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

Gillespie, L.K.

1978-01-01

An annotated summary of 204 articles and publications on burrs, burr prevention and deburring is presented. Thirty-seven deburring processes are listed. Entries cited include English, Russian, French, Japanese and German language articles. Entries are indexed by deburring processes, author, and language. Indexes also indicate which references discuss equipment and tooling, how to use a process, economics, burr properties, and how to design to minimize burr problems. Research studies are identified as are the materials deburred.

HSV-1 infection of human corneal epithelial cells: receptor-mediated entry and trends of re-infection.

PubMed

Shah, Arpeet; Farooq, Asim V; Tiwari, Vaibhav; Kim, Min-Jung; Shukla, Deepak

2010-11-20

The human cornea is a primary target for herpes simplex virus-1 (HSV-1) infection. The goals of the study were to determine the cellular modalities of HSV-1 entry into human corneal epithelial (HCE) cells. Specific features of the study included identifying major entry receptors, assessing pH dependency, and determining trends of re-infection. A recombinant HSV-1 virus expressing beta-galactosidase was used to ascertain HSV-1 entry into HCE cells. Viral replication within cells was confirmed using a time point plaque assay. Lysosomotropic agents were used to test for pH dependency of entry. Flow cytometry and immunocytochemistry were used to determine expression of three cellular receptors--nectin-1, herpesvirus entry mediator (HVEM), and paired immunoglobulin-like 2 receptor alpha (PILR-a). The necessity of these receptors for viral entry was tested using antibody-blocking. Finally, trends of re-infection were investigated using viral entry assay and flow cytometry post-primary infection. Cultured HCE cells showed high susceptibility to HSV-1 entry and replication. Entry was demonstrated to be pH dependent as blocking vesicular acidification decreased entry. Entry receptors expressed on the cell membrane include nectin-1, HVEM, and PILR-α. Receptor-specific antibodies blocked entry receptors, reduced viral entry and indicated nectin-1 as the primary receptor used for entry. Cells re-infected with HSV-1 showed a decrease in entry, which was correlated to decreased levels of nectin-1 as demonstrated by flow cytometry. HSV-1 is capable of developing an infection in HCE cells using a pH dependent entry process that involves primarily nectin-1 but also the HVEM and PILR-α receptors. Re-infected cells show decreased levels of entry, correlated with a decreased level of nectin-1 receptor expression.

A Genetic Interaction between the Core and NS3 Proteins of Hepatitis C Virus Is Essential for Production of Infectious Virus▿†

PubMed Central

Jones, Daniel M.; Atoom, Ali M.; Zhang, Xiaozhen; Kottilil, Shyamasundaran; Russell, Rodney S.

2011-01-01

By analogy to other members of the Flaviviridae family, the hepatitis C virus (HCV) core protein is presumed to oligomerize to form the viral nucleocapsid, which encloses the single-stranded RNA genome. Core protein is directed to lipid droplets (LDs) by domain 2 (D2) of the protein, and this process is critical for virus production. Domain 1 (D1) of core is also important for infectious particle morphogenesis, although its precise contribution to this process is poorly understood. In this study, we mutated amino acids 64 to 75 within D1 of core and examined the ability of these mutants to produce infectious virus. We found that residues 64 to 66 are critical for generation of infectious progeny, whereas 67 to 75 were dispensable for this process. Further investigation of the defective 64 to 66 mutant (termed JFH1T-64–66) revealed it to be incapable of producing infectious intracellular virions, suggesting a fault during HCV assembly. Furthermore, isopycnic gradient analyses revealed that JFH1T-64–66 assembled dense intracellular species of core, presumably representing nucleocapsids. Thus, amino acids 64 to 66 are seemingly not involved in core oligomerization/nucleocapsid assembly. Passaging of JFH1T-64–66 led to the emergence of a single compensatory mutation (K1302R) within the helicase domain of NS3 that completely rescued its ability to produce infectious virus. Importantly, the same NS3 mutation abrogated virus production in the context of wild-type core protein. Together, our results suggest that residues 64 to 66 of core D1 form a highly specific interaction with the NS3 helicase that is essential for the generation of infectious HCV particles at a stage downstream of nucleocapsid assembly. PMID:21957313

Genesis Sample Return Capsule Overview

NASA Technical Reports Server (NTRS)

Willcockson, Bill

2005-01-01

I. Simple Entry Capsule Concept: a) Spin-Stabilized/No Active Control Systems; b) Ballistic Entry for 11.04 km/sec Velocity; c) No Heatshield Separation During Entry; d) Parachute Deploy via g-Switch + Timer. II. Stardust Design Inheritance a) Forebody Shape; b) Seal Concepts; c) Parachute Deploy Control; d) Utah Landing Site (UTTR). III. TPS Systems a) Heatshield - Carbon-Carbon - First Planetary Entry; b) Backshell - SLA-561V - Flight Heritage from Pathfinder, MER; d) Forebody Structural Penetrations Aerothermal and TPS Design Process has the Same Methodology as Used for Pathfinder, MER Flight Vehicles.

Systems thinking in combating infectious diseases.

PubMed

Xia, Shang; Zhou, Xiao-Nong; Liu, Jiming

2017-09-11

The transmission of infectious diseases is a dynamic process determined by multiple factors originating from disease pathogens and/or parasites, vector species, and human populations. These factors interact with each other and demonstrate the intrinsic mechanisms of the disease transmission temporally, spatially, and socially. In this article, we provide a comprehensive perspective, named as systems thinking, for investigating disease dynamics and associated impact factors, by means of emphasizing the entirety of a system's components and the complexity of their interrelated behaviors. We further develop the general steps for performing systems approach to tackling infectious diseases in the real-world settings, so as to expand our abilities to understand, predict, and mitigate infectious diseases.

Biosafety considerations for attenuated measles virus vectors used in virotherapy and vaccination.

PubMed

Baldo, Aline; Galanis, Evanthia; Tangy, Frédéric; Herman, Philippe

2016-05-03

Attenuated measles virus (MV) is one of the most effective and safe vaccines available, making it attractive candidate vector to prevent infectious diseases. Attenuated MV have acquired the ability to use the complement regulator CD46 as a major receptor to mediate virus entry and intercellular fusion. Therefore, attenuated MV strains preferentially infect and destroy a wide variety of cancer cells making them also attractive oncolytic vectors. The use of recombinant MV vector has to comply with various regulatory requirements, particularly relating to the assessment of potential risks for human health and the environment. The present article highlights the main characteristics of MV and recombinant MV vectors used for vaccination and virotherapy and discusses these features from a biosafety point of view.

Influenza A Virus Encoding Secreted Gaussia Luciferase as Useful Tool to Analyze Viral Replication and Its Inhibition by Antiviral Compounds and Cellular Proteins

PubMed Central

Palanisamy, Navaneethan; Goedecke, Ulrike; Jäger, Nils; Pöhlmann, Stefan; Winkler, Michael

2014-01-01

Reporter genes inserted into viral genomes enable the easy and rapid quantification of virus replication, which is instrumental to efficient in vitro screening of antiviral compounds or in vivo analysis of viral spread and pathogenesis. Based on a published design, we have generated several replication competent influenza A viruses carrying either fluorescent proteins or Gaussia luciferase. Reporter activity could be readily quantified in infected cultures, but the virus encoding Gaussia luciferase was more stable than viruses bearing fluorescent proteins and was therefore analyzed in detail. Quantification of Gaussia luciferase activity in the supernatants of infected culture allowed the convenient and highly sensitive detection of viral spread, and enzymatic activity correlated with the number of infectious particles released from infected cells. Furthermore, the Gaussia luciferase encoding virus allowed the sensitive quantification of the antiviral activity of the neuraminidase inhibitor (NAI) zanamivir and the host cell interferon-inducible transmembrane (IFITM) proteins 1–3, which are known to inhibit influenza virus entry. Finally, the virus was used to demonstrate that influenza A virus infection is sensitive to a modulator of endosomal cholesterol, in keeping with the concept that IFITMs inhibit viral entry by altering cholesterol levels in the endosomal membrane. In sum, we report the characterization of a novel influenza A reporter virus, which allows fast and sensitive detection of viral spread and its inhibition, and we show that influenza A virus entry is sensitive to alterations of endosomal cholesterol levels. PMID:24842154

Stepwise Priming by Acidic pH and a High K+ Concentration Is Required for Efficient Uncoating of Influenza A Virus Cores after Penetration

PubMed Central

Feng, Yuehan; Nebioglu, Firat; Heilig, Rosalie; Picotti, Paola

2014-01-01

ABSTRACT Influenza A virus (IAV) uses the low pH in late endocytic vacuoles as a cue for penetration by membrane fusion. Here, we analyzed the prefusion reactions that prepare the core for uncoating after it has been delivered to the cytosol. We found that this priming process occurs in two steps that are mediated by the envelope-embedded M2 ion channel. The first weakens the interactions between the matrix protein, M1, and the viral ribonucleoprotein bundle. It involves a conformational change in a linker sequence and the C-terminal domain of M1 after exposure to a pH below 6.5. The second step is triggered by a pH of <6.0 and by the influx of K+ ions. It causes additional changes in M1 as well as a loss of stability in the viral ribonucleoprotein bundle. Our results indicate that both the switch from Na+ to K+ in maturing endosomes and the decreasing pH are needed to prime IAV cores for efficient uncoating and infection of the host cell. IMPORTANCE The entry of IAV involves several steps, including endocytosis and fusion at late endosomes. Entry also includes disassembly of the viral core, which is composed of the viral ribonucleoproteins and the RNA genome. We have found that the uncoating process of IAV is initiated long before the core is delivered into the cytosol. M2, an ion channel in the viral membrane, is activated when the virus passes through early endosomes. Here, we show that protons entering the virus through M2 cause a conformational change in the matrix protein, M1. This weakens interactions between M1 and the viral ribonucleoproteins. A second change was found to occur when the virus enters late endosomes. The preacidified core is then exposed to a high concentration of K+, which affects the interactions between the ribonucleoproteins. Thus, when cores are finally delivered to the cytosol, they are already partially destabilized and, therefore, uncoating competent and infectious. PMID:25165113

Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology

PubMed Central

Michael, Benedict D.; Griffiths, Michael J.; Granerod, Julia; Brown, David; Davies, Nicholas W. S.; Borrow, Ray; Solomon, Tom

2016-01-01

Background Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15–60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause. Methods We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology. Results Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001). Conclusions Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation. PMID:26808276

Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology.

PubMed

Michael, Benedict D; Griffiths, Michael J; Granerod, Julia; Brown, David; Davies, Nicholas W S; Borrow, Ray; Solomon, Tom

2016-01-01

Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause. We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology. Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001). Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.

Creating a process for incorporating epidemiological modelling into outbreak management decisions.

PubMed

Akselrod, Hana; Mercon, Monica; Kirkeby Risoe, Petter; Schlegelmilch, Jeffrey; McGovern, Joanne; Bogucki, Sandy

2012-01-01

Modern computational models of infectious diseases greatly enhance our ability to understand new infectious threats and assess the effects of different interventions. The recently-released CDC Framework for Preventing Infectious Diseases calls for increased use of predictive modelling of epidemic emergence for public health preparedness. Currently, the utility of these technologies in preparedness and response to outbreaks is limited by gaps between modelling output and information requirements for incident management. The authors propose an operational structure that will facilitate integration of modelling capabilities into action planning for outbreak management, using the Incident Command System (ICS) and Synchronization Matrix framework. It is designed to be adaptable and scalable for use by state and local planners under the National Response Framework (NRF) and Emergency Support Function #8 (ESF-8). Specific epidemiological modelling requirements are described, and integrated with the core processes for public health emergency decision support. These methods can be used in checklist format to align prospective or real-time modelling output with anticipated decision points, and guide strategic situational assessments at the community level. It is anticipated that formalising these processes will facilitate translation of the CDC's policy guidance from theory to practice during public health emergencies involving infectious outbreaks.

The evolutions of medical building network structure for emerging infectious disease protection and control.

PubMed

Liu, Nan; Zhang, Hongzhe; Zhang, Shanshan

2014-12-01

Emerging infectious disease is one of the most minatory threats in modern society. A perfect medical building network system need to be established to protect and control emerging infectious disease. Although in China a preliminary medical building network is already set up with disease control center, the infectious disease hospital, infectious diseases department in general hospital and basic medical institutions, there are still many defects in this system, such as simple structural model, weak interoperability among subsystems, and poor capability of the medical building to adapt to outbreaks of infectious disease. Based on the characteristics of infectious diseases, the whole process of its prevention and control and the comprehensive influence factors, three-dimensional medical architecture network system is proposed as an inevitable trend. In this conception of medical architecture network structure, the evolutions are mentioned, such as from simple network system to multilayer space network system, from static network to dynamic network, and from mechanical network to sustainable network. Ultimately, a more adaptable and corresponsive medical building network system will be established and argued in this paper.

Framework for Infectious Disease Analysis: A comprehensive and integrative multi-modeling approach to disease prediction and management.

PubMed

Erraguntla, Madhav; Zapletal, Josef; Lawley, Mark

2017-12-01

The impact of infectious disease on human populations is a function of many factors including environmental conditions, vector dynamics, transmission mechanics, social and cultural behaviors, and public policy. A comprehensive framework for disease management must fully connect the complete disease lifecycle, including emergence from reservoir populations, zoonotic vector transmission, and impact on human societies. The Framework for Infectious Disease Analysis is a software environment and conceptual architecture for data integration, situational awareness, visualization, prediction, and intervention assessment. Framework for Infectious Disease Analysis automatically collects biosurveillance data using natural language processing, integrates structured and unstructured data from multiple sources, applies advanced machine learning, and uses multi-modeling for analyzing disease dynamics and testing interventions in complex, heterogeneous populations. In the illustrative case studies, natural language processing from social media, news feeds, and websites was used for information extraction, biosurveillance, and situation awareness. Classification machine learning algorithms (support vector machines, random forests, and boosting) were used for disease predictions.

Thermophysics Issues Relevant to High-Speed Earth Entry of Large Asteroids

NASA Technical Reports Server (NTRS)

Prabhu, D.; Saunders, D.; Agrawal, P.; Allen, G.; Bauschlicher, C.; Brandis, A.; Chen, Y.-K.; Jaffe, R.; Schulz, J.; Stern, E.;

Timing is everything: Fine-tuned molecular machines orchestrate paramyxovirus entry

PubMed Central

Bose, Sayantan; Jardetzky, Theodore S.; Lamb, Robert A.

2015-01-01

The Paramyxoviridae include some of the great and ubiquitous disease-causing viruses of humans and animals. In most paramyxoviruses, two viral membrane glycoproteins, fusion protein (F) and receptor binding protein (HN, H or G) mediate a concerted process of recognition of host cell surface molecules followed by fusion of viral and cellular membranes, resulting in viral nucleocapsid entry into the cytoplasm. The interactions between the F and HN, H or G viral glycoproteins and host molecules are critical in determining host range, virulence and spread of these viruses. Recently, atomic structures, together with biochemical and biophysical studies, have provided major insights into how these two viral glycoproteins successfully interact with host receptors on cellular membranes and initiate the membrane fusion process to gain entry into cells. These studies highlight the conserved core mechanisms of paramyxovirus entry that provide the fundamental basis for rational anti-viral drug design and vaccine development. PMID:25771804

Paramyxovirus fusion and entry: multiple paths to a common end.

PubMed

Chang, Andres; Dutch, Rebecca E

2012-04-01

The paramyxovirus family contains many common human pathogenic viruses, including measles, mumps, the parainfluenza viruses, respiratory syncytial virus, human metapneumovirus, and the zoonotic henipaviruses, Hendra and Nipah. While the expression of a type 1 fusion protein and a type 2 attachment protein is common to all paramyxoviruses, there is considerable variation in viral attachment, the activation and triggering of the fusion protein, and the process of viral entry. In this review, we discuss recent advances in the understanding of paramyxovirus F protein-mediated membrane fusion, an essential process in viral infectivity. We also review the role of the other surface glycoproteins in receptor binding and viral entry, and the implications for viral infection. Throughout, we concentrate on the commonalities and differences in fusion triggering and viral entry among the members of the family. Finally, we highlight key unanswered questions and how further studies can identify novel targets for the development of therapeutic treatments against these human pathogens.

An Analysis of United States Marine Corps Enlisted Entry-Level Training Using Supply Chain and Operations Management

DTIC Science & Technology

2010-12-01

An Analysis of United States Marine Corps Enlisted Entry-Level Training Using Supply Chain and Operations Management ______________________________________ By...Report 4. TITLE AND SUBTITLE: An Analysis of United States Marine Corps Enlisted Entry-Level Training Using Supply Chain and Operations Management 6...Level Training; United States Marine Corps; Operations Management ; Supply Chain Management; Process Analysis 16. PRICE CODE 17. SECURITY

A multi-criteria assessment of scenarios on thermal processing of infectious hospital wastes: A case study for Central Macedonia

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

Karagiannidis, A.; Papageorgiou, A., E-mail: apapa@auth.g; Perkoulidis, G.

In Greece more than 14,000 tonnes of infectious hospital waste are produced yearly; a significant part of it is still mismanaged. Only one off-site licensed incineration facility for hospital wastes is in operation, with the remaining of the market covered by various hydroclave and autoclave units, whereas numerous problems are still generally encountered regarding waste segregation, collection, transportation and management, as well as often excessive entailed costs. Everyday practices still include dumping the majority of solid hospital waste into household disposal sites and landfills after sterilization, still largely without any preceding recycling and separation steps. Discussed in the present papermore » are the implemented and future treatment practices of infectious hospital wastes in Central Macedonia; produced quantities are reviewed, actual treatment costs are addressed critically, whereas the overall situation in Greece is discussed. Moreover, thermal treatment processes that could be applied for the treatment of infectious hospital wastes in the region are assessed via the multi-criteria decision method Analytic Hierarchy Process. Furthermore, a sensitivity analysis was performed and the analysis demonstrated that a centralized autoclave or hydroclave plant near Thessaloniki is the best performing option, depending however on the selection and weighing of criteria of the multi-criteria process. Moreover the study found that a common treatment option for the treatment of all infectious hospital wastes produced in the Region of Central Macedonia, could offer cost and environmental benefits. In general the multi-criteria decision method, as well as the conclusions and remarks of this study can be used as a basis for future planning and anticipation of the needs for investments in the area of medical waste management.« less

Design and Development of a Prototype Organizational Effectiveness Information System

DTIC Science & Technology

1984-11-01

information from a large number of people. The existing survey support process for the GOQ is not satisfac- * tory. Most OESOs elect not to use it, because...reporting process uses screen queries and menus to simplify data entry, it is estimated that only 4-6 hours of data entry time would be required for ...description for the file named EVEDIR. The Resource System allows users of the Event Directory to select from the following processing options. o Add a new

The ubiquitin-proteasome system is essential for the productive entry of Japanese encephalitis virus.

PubMed

Wang, Shaobo; Liu, Haibin; Zu, Xiangyang; Liu, Yang; Chen, Liman; Zhu, Xueqin; Zhang, Leike; Zhou, Zheng; Xiao, Gengfu; Wang, Wei

2016-11-01

The host-virus interaction during the cellular entry of Japanese encephalitis virus (JEV) is poorly characterized. The ubiquitin-proteasome system (UPS), the major intracellular proteolytic pathway, mediates diverse cellular processes, including endocytosis and signal transduction, which may be involved in the entry of virus. Here, we showed that the proteasome inhibitors, MG132 and lactacystin, impaired the productive entry of JEV by effectively interfering with viral intracellular trafficking at the stage between crossing cell membrane and the initial translation of the viral genome after uncoating. Using confocal microscopy, it was demonstrated that a proportion of the internalized virions were misdirected to lysosomes following treatment with MG132, resulting in non-productive entry. In addition, using specific siRNAs targeting ubiquitin, we verified that protein ubiquitination was involved in the entry of JEV. Overall, our study demonstrated the UPS is essential for the productive entry of JEV and might represent a potential antiviral target for JEV infection. Copyright © 2016 Elsevier Inc. All rights reserved.

Questions and Answers Regarding the 2009 New Source Performance Standards (NSPS) Emissions Guidelines, and State Plan Process for Hospital, Medical, and Infectious Waste Incinerators (HMIWI)

EPA Pesticide Factsheets

This July 2011 document contains questions and answers on the Hospital/Medical/Infectious Waste Incinerators (HMIWI) regulations. The questions cover topics such as state plan requirements, compliance, applicability, operator training, and more.

"Our commonality is our past:" a qualitative analysis of re-entry community health workers' meaningful experiences.

PubMed

Bedell, Precious; Wilson, John L; White, Ann Marie; Morse, Diane S

Re-entry community health workers (CHWs) are individuals who connect diverse community residents at risk for chronic health issues such as Hepatitis C virus and cardiovascular disease with post-prison healthcare and re-entry services. While the utilization of CHWs has been documented in other marginalized populations, there is little knowledge surrounding the work of re-entry CHWs with individuals released from incarceration. Specifically, CHWs' experiences and perceptions of the uniqueness of their efforts to link individuals to healthcare have not been documented systematically. This study explored what is meaningful to formerly incarcerated CHWs as they work with released individuals. The authors conducted a qualitative thematic analysis of twelve meaningful experiences written by re-entry CHWs employed by the Transitions Clinic Network who attended a CHW training program during a conference in San Francisco, CA. Study participants were encouraged to recount meaningful CHW experiences and motivations for working with re-entry populations in a manner consistent with journal-based qualitative analysis techniques. Narratives were coded using an iterative process and subsequently organized according to themes in ATLAS.ti. Study personnel came to consensus with coding and major themes. The narratives highlighted thought processes and meaning related to re-entry CHWs' work helping patients navigate complex social services for successful re-integration. Six major themes emerged from the analysis: advocacy and support, empathy relating to a personal history of incarceration, giving back, professional satisfaction and responsibilities, resiliency and educational advancement, and experiences of social inequities related to race. Re-entry CHWs described former incarceration, employment, and social justice as sources of meaning for assisting justice-involved individuals receive effective, efficient, and high-quality healthcare. Health clinics for individuals released from incarceration provide a unique setting that links high risk patients to needed care and professionalizes career opportunities for formerly incarcerated re-entry CHWs. The commonality of past correctional involvement is a strong indicator of the meaning and perceived effectiveness re-entry CHWs find in working with individuals leaving prison. Expansion of reimbursable visits with re-entry CHWs in transitions clinics designed for re-entering individuals is worthy of further consideration.

Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses.

PubMed

Tay, Matthew Zirui; Liu, Pinghuang; Williams, LaTonya D; McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T; Dennison, S Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S Munir; Moody, M Anthony; Hope, Thomas J; Haynes, Barton F; Tomaras, Georgia D

2016-08-01

Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine-induced antibodies and therapeutic antibodies will enable a better understanding of their capacity to prevent and/or control HIV-1 infection in vivo.

Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses

PubMed Central

McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T.; Dennison, S. Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S. Munir; Haynes, Barton F.; Tomaras, Georgia D.

2016-01-01

Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine-induced antibodies and therapeutic antibodies will enable a better understanding of their capacity to prevent and/or control HIV-1 infection in vivo. PMID:27579713

TIM1 (HAVCR1) Is Not Essential for Cellular Entry of Either Quasi-enveloped or Naked Hepatitis A Virions.

PubMed

Das, Anshuman; Hirai-Yuki, Asuka; González-López, Olga; Rhein, Bethany; Moller-Tank, Sven; Brouillette, Rachel; Hensley, Lucinda; Misumi, Ichiro; Lovell, William; Cullen, John M; Whitmire, Jason K; Maury, Wendy; Lemon, Stanley M

2017-09-05

Receptor molecules play key roles in the cellular entry of picornaviruses, and TIM1 (HAVCR1) is widely accepted to be the receptor for hepatitis A virus (HAV), an unusual, hepatotropic human picornavirus. However, its identification as the hepatovirus receptor predated the discovery that hepatoviruses undergo nonlytic release from infected cells as membrane-cloaked, quasi-enveloped HAV (eHAV) virions that enter cells via a pathway distinct from naked, nonenveloped virions. We thus revisited the role of TIM1 in hepatovirus entry, examining both adherence and infection/replication in cells with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-engineered TIM1 knockout. Cell culture-derived, gradient-purified eHAV bound Huh-7.5 human hepatoma cells less efficiently than naked HAV at 4°C, but eliminating TIM1 expression caused no difference in adherence of either form of HAV, nor any impact on infection and replication in these cells. In contrast, TIM1-deficient Vero cells showed a modest reduction in quasi-enveloped eHAV (but not naked HAV) attachment and replication. Thus, TIM1 facilitates quasi-enveloped eHAV entry in Vero cells, most likely by binding phosphatidylserine (PtdSer) residues on the eHAV membrane. Both Tim1 -/- Ifnar1 -/- and Tim4 -/- Ifnar1 -/- double-knockout mice were susceptible to infection upon intravenous challenge with infected liver homogenate, with fecal HAV shedding and serum alanine aminotransferase (ALT) elevations similar to those in Ifnar1 -/- mice. However, intrahepatic HAV RNA and ALT elevations were modestly reduced in Tim1 -/- Ifnar1 -/- mice compared to Ifnar1 -/- mice challenged with a lower titer of gradient-purified HAV or eHAV. We conclude that TIM1 is not an essential hepatovirus entry factor, although its PtdSer-binding activity may contribute to the spread of quasi-enveloped virus and liver injury in mice. IMPORTANCE T cell immunoglobulin and mucin-containing domain protein 1 (TIM1) was reported more than 2 decades ago to be an essential cellular receptor for hepatitis A virus (HAV), a picornavirus in the Hepatovirus genus, resulting in its designation as "hepatitis A virus cellular receptor 1" (HAVCR1) by the Human Genome Organization Gene Nomenclature Committee. However, recent studies have shown that HAV exists in nature as both naked, nonenveloped (HAV) virions and membrane-cloaked, quasi-enveloped infectious virus (eHAV), prompting us to revisit the role of TIM1 in viral entry. We show here that TIM1 (HAVCR1) is not an essential cellular receptor for HAV entry into cultured cells or required for viral replication and pathogenesis in permissive strains of mice, although it may facilitate early stages of infection by binding phosphatidylserine on the eHAV surface. This work thus corrects the published record and sets the stage for future efforts to identify specific hepatovirus entry factors. Copyright © 2017 Das et al.

Infectious Hepatitis C Virus Pseudo-particles Containing Functional E1–E2 Envelope Protein Complexes

PubMed Central

Bartosch, Birke; Dubuisson, Jean; Cosset, François-Loïc

2003-01-01

The study of hepatitis C virus (HCV), a major cause of chronic liver disease, has been hampered by the lack of a cell culture system supporting its replication. Here, we have successfully generated infectious pseudo-particles that were assembled by displaying unmodified and functional HCV glycoproteins onto retroviral and lentiviral core particles. The presence of a green fluorescent protein marker gene packaged within these HCV pseudo-particles allowed reliable and fast determination of infectivity mediated by the HCV glycoproteins. Primary hepatocytes as well as hepato-carcinoma cells were found to be the major targets of infection in vitro. High infectivity of the pseudo-particles required both E1 and E2 HCV glycoproteins, and was neutralized by sera from HCV-infected patients and by some anti-E2 monoclonal antibodies. In addition, these pseudo-particles allowed investigation of the role of putative HCV receptors. Although our results tend to confirm their involvement, they provide evidence that neither LDLr nor CD81 is sufficient to mediate HCV cell entry. Altogether, these studies indicate that these pseudo-particles may mimic the early infection steps of parental HCV and will be suitable for the development of much needed new antiviral therapies. PMID:12615904

Epidemiology of tetanus in the Marches Region of Italy, 1992-95.

PubMed Central

Prospero, E.; Appignanesi, R.; D'Errico, M. M.; Carle, F.

1998-01-01

Reported is the incidence of tetanus in the Marches Region of Italy for the period 1992-95. Data were obtained from both the regional public health committee's notification forms for infectious diseases and from hospital clinical records. A total of 36 cases were examined, comprising 7 males (19.4%) and 29 females. The raw annual incidence was 6.3 per million population; the standardized incidence for females was four times greater than that for males (9.2 and 2.4 per million population annually, respectively). The patients' ages varied from 31 years to 88 years (median, 73.5 years). The incidence among subjects older than 65 years was approximately ten times greater than that among younger individuals. Chronic wounds, such as trophic lesions, represented the site of tetanus infection in 14.3% of cases whose infection entry point was identified. Treatment of the 36 cases required a total of 1239 hospital days, of which 58.7% were in intensive care and 29.6% were in infectious diseases departments. The raw annual mortality rate for the period considered was 0.7 per million population; the case-fatality ratio was 11%. The results of our study confirm the limits of the current Italian immunization programmes, which exclude a large portion of the population from antitetanus protection. PMID:9615496

Activation of B Cells by a Dendritic Cell-Targeted Oral Vaccine

PubMed Central

Sahay, Bikash; Owen, Jennifer L.; Yang, Tao; Zadeh, Mojgan; Lightfoot, Yaíma L.; Ge, Jun-Wei; Mohamadzadeh, Mansour

2015-01-01

Production of long-lived, high affinity humoral immunity is an essential characteristic of successful vaccination and requires cognate interactions between T and B cells in germinal centers. Within germinal centers, specialized T follicular helper cells assist B cells and regulate the antibody response by mediating the differentiation of B cells into memory or plasma cells after exposure to T cell-dependent antigens. It is now appreciated that local immune responses are also essential for protection against infectious diseases that gain entry to the host by the mucosal route; therefore, targeting the mucosal compartments is the optimum strategy to induce protective immunity. However, because the gastrointestinal mucosae are exposed to large amounts of environmental and dietary antigens on a daily basis, immune regulatory mechanisms exist to favor tolerance and discourage autoimmunity at these sites. Thus, mucosal vaccination strategies must ensure that the immunogen is efficiently taken up by the antigen presenting cells, and that the vaccine is capable of activating humoral and cellular immunity, while avoiding the induction of tolerance. Despite significant progress in mucosal vaccination, this potent platform for immunotherapy and disease prevention must be further explored and refined. Here we discuss recent progress in the understanding of the role of different phenotypes of B cells in the development of an efficacious mucosal vaccine against infectious disease. PMID:24372255

Emerging infectious diseases in southeast Asia: regional challenges to control.

PubMed

Coker, Richard J; Hunter, Benjamin M; Rudge, James W; Liverani, Marco; Hanvoravongchai, Piya

2011-02-12

Southeast Asia is a hotspot for emerging infectious diseases, including those with pandemic potential. Emerging infectious diseases have exacted heavy public health and economic tolls. Severe acute respiratory syndrome rapidly decimated the region's tourist industry. Influenza A H5N1 has had a profound effect on the poultry industry. The reasons why southeast Asia is at risk from emerging infectious diseases are complex. The region is home to dynamic systems in which biological, social, ecological, and technological processes interconnect in ways that enable microbes to exploit new ecological niches. These processes include population growth and movement, urbanisation, changes in food production, agriculture and land use, water and sanitation, and the effect of health systems through generation of drug resistance. Southeast Asia is home to about 600 million people residing in countries as diverse as Singapore, a city state with a gross domestic product (GDP) of US$37,500 per head, and Laos, until recently an overwhelmingly rural economy, with a GDP of US$890 per head. The regional challenges in control of emerging infectious diseases are formidable and range from influencing the factors that drive disease emergence, to making surveillance systems fit for purpose, and ensuring that regional governance mechanisms work effectively to improve control interventions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Label-Free Quantitative Proteomic Analysis of Harmless and Pathogenic Strains of Infectious Microalgae, Prototheca spp.

PubMed Central

Murugaiyan, Jayaseelan; Eravci, Murat; Weise, Christoph; Roesler, Uwe

2016-01-01

Microalgae of the genus Prototheca (P.) spp are associated with rare algal infections of invertebrates termed protothecosis. Among the seven generally accepted species, P. zopfii genotype 2 (GT2) is associated with a severe form of bovine mastitis while P. blaschkeae causes the mild and sub-clinical form of mastitis. The reason behind the infectious nature of P. zopfii GT2, while genotype 1 (GT1) remains non-infectious, is not known. Therefore, in the present study we investigated the protein expression level difference between the genotypes of P. zopfii and P. blaschkeae. Cells were cultured to the mid-exponential phase, harvested, and processed for LC-MS analysis. Peptide data was acquired on an LTQ Orbitrap Velos, raw spectra were quantitatively analyzed with MaxQuant software and matching with the reference database of Chlorella variabilis and Auxenochlorella protothecoides resulted in the identification of 226 proteins. Comparison of an environmental strain with infectious strains resulted in the identification of 51 differentially expressed proteins related to carbohydrate metabolism, energy production and protein translation. The expression level of Hsp70 proteins and their role in the infectious process is worth further investigation. All mass spectrometry data are available via ProteomeXchange with identifier PXD005305. PMID:28036087

Training, Retention, and Transfer of Data Entry Perceptual and Motoric Processes Over Long Retention Intervals

NASA Technical Reports Server (NTRS)

Kole, James A.; Schneider, Vivian I.; Healy, Alice F.; Barshi, Immanuel

2017-01-01

Subjects trained in a standard data entry task, which involved typing numbers (e.g., 5421) using their right hands. At test (6 months post-training), subjects completed the standard task, followed by a left-hand variant (typing with their left hands) that involved the same perceptual, but different motoric, processes as the standard task. At a second test (8 months post-training), subjects completed the standard task, followed by a code variant (translating letters into digits, then typing the digits with their right hands) that involved different perceptual, but the same motoric, processes as the standard task. For each of the three tasks, half the trials were trained numbers (old) and half were new. Repetition priming (faster response times to old than new numbers) was found for each task. Repetition priming for the standard task reflects retention of trained numbers; for the left-hand variant reflects transfer of perceptual processes; and for the code variant reflects transfer of motoric processes. There was thus evidence for both specificity and generalizability of training data entry perceptual and motoric processes over very long retention intervals.

The Correlates and Consequences of Welfare Exit and Entry: Evidence from the Three-City Study. Working Paper.

ERIC Educational Resources Information Center

Moffitt, Robert; Winder, Katie

The dramatic decline in Temporary Assistance for Needy Families (TANF) caseloads in the 1990s has focused attention on the process of exit from, and, to a lesser extent, entry into, the welfare system. This paper charts the process of turnover in the TANF program in three major U.S. cities over an 18-month, post-PWORA period and documents its…

Structural, functional, and evolutionary aspects of galectins in aquatic mollusks: From a sweet tooth to the Trojan horse

PubMed Central

Vasta, GR; Feng, C; Bianchet, MA; Bachvaroff, TR; Tasumi, S

2015-01-01

Galectins constitute a conserved and widely distributed lectin family characterized by their binding affinity for β-galactosides and a unique binding site sequence motif in the carbohydrate recognition domain (CRD). In spite of their structural conservation, galectins display a remarkable functional diversity, by participating in developmental processes, cell adhesion and motility, regulation of immune homeostasis, and recognition of glycans on the surface of viruses, bacteria and protozoan parasites. In contrast with mammals, and other vertebrate and invertebrate taxa, the identification and characterization of bona fide galectins in aquatic mollusks has been relatively recent. Most of the studies have focused on the identification and domain organization of galectin-like transcripts or proteins in diverse tissues and cell types, including hemocytes, and their expression upon environmental or infectious challenge. Lectins from the eastern oyster Crassostrea virginica, however, have been characterized in their molecular, structural and functional aspects and some notable features have become apparent in the galectin repertoire of aquatic mollusks. These including less diversified galectin repertoires and different domain organizations relative to those observed in vertebrates, carbohydrate specificity for blood group oligosaccharides, and up regulation of galectin expression by infectious challenge, a feature that supports their proposed role(s) in innate immune responses. Although galectins from some aquatic mollusks have been shown to recognize microbial pathogens and parasites and promote their phagocytosis, they can also selectively bind to phytoplankton components, suggesting that they also participate in uptake and intracellular digestion of microalgae. In addition, the experimental evidence suggests that the protozoan parasite Perkinsus marinus has co-evolved with the oyster host to be selectively recognized by the oyster hemocyte galectins over algal food or bacterial pathogens, thereby subverting the oyster’s innate immune/feeding recognition mechanisms to gain entry into the host cells. PMID:25982395

Challenges to the implementation of International Health Regulations (2005) on Preventing Infectious Diseases: experience from Julius Nyerere International Airport, Tanzania

PubMed Central

Bakari, Edith; Frumence, Gasto

2013-01-01

Background The International Health Regulations (IHR) (2005) is a legal instrument binding all World Health Organization (WHO) member States. It aims to prevent and control public health emergencies of international concern. Country points of entry (POEs) have been identified as potential areas for effective interventions to prevent the transmission of infectious diseases across borders. The agreement postulates that member states will strengthen core capacities detailed in the IHR (2005), including those specified for the POE. This study intended to assess the challenges faced in implementing the IHR (2005) requirements at Julius Nyerere International Airport (JNIA), Dar es Salaam. Design A cross-sectional, descriptive study, employing qualitative methods, was conducted at the Ministry of Health and Social Welfare (MoHSW), WHO, and JNIA. In-depth interviews, focus group discussions (FGDs) and documentary reviews were used to obtain relevant information. Respondents were purposively enrolled into the study. Thematic analysis was used to generate study findings. Results Several challenges that hamper implementation of the IHR (2005) were identified: (1) none of the 42 Tanzanian POEs have been specifically designated to implement IHR (2005). (2) Implementation of the IHR (2005) at the POE was complicated as it falls under various uncoordinated government departments. Although there were clear communication channels at JNIA that enhanced reliable risk communication, the airport lacked isolated rooms specific for emergence preparedness and response to public health events. Conclusions JNIA is yet to develop adequate core capacities required for implementation of the IHR (2005). There is a need for policy managers to designate JNIA to implement IHR (2005) and ensure that public health policies, legislations, guidelines, and practice at POE are harmonized to improve international travel and trade. Policy makers and implementers should also ensure that implementation of the IHR (2005) follow the policy implementation framework, particularly the contextual interaction theory which calls for the availability of adequate resources (inputs) and well-organized process for the successful implementation of the policy. PMID:23958240

The small envelope protein of porcine reproductive and respiratory syndrome virus possesses ion channel protein-like properties

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

Lee, Changhee; Yoo, Dongwan

The small envelope (E) protein of porcine reproductive and respiratory syndrome virus (PRRSV) is a hydrophobic 73 amino acid protein encoded in the internal open reading frame (ORF) of the bicistronic mRNA2. As a first step towards understanding the biological role of E protein during PRRSV replication, E gene expression was blocked in a full-length infectious clone by mutating the ATG translational initiation to GTG, such that the full-length mutant genomic clone was unable to synthesize the E protein. DNA transfection of PRRSV-susceptible cells with the E gene knocked-out genomic clone showed the absence of virus infectivity. P129-{delta}E-transfected cells howevermore » produced virion particles in the culture supernatant, and these particles contained viral genomic RNA, demonstrating that the E protein is essential for PRRSV infection but dispensable for virion assembly. Electron microscopy suggests that the P129-{delta}E virions assembled in the absence of E had a similar appearance to the wild-type particles. Strand-specific RT-PCR demonstrated that the E protein-negative, non-infectious P129-{delta}E virus particles were able to enter cells but further steps of replication were interrupted. The entry of PRRSV has been suggested to be via receptor-mediated endocytosis, and lysomotropic basic compounds and known ion-channel blocking agents both inhibited PRRSV replication effectively during the uncoating process. The expression of E protein in Escherichia coli-mediated cell growth arrests and increased the membrane permeability. Cross-linking experiments in cells infected with PRRSV or transfected with E gene showed that the E protein was able to form homo-oligomers. Taken together, our data suggest that the PRRSV E protein is likely an ion-channel protein embedded in the viral envelope and facilitates uncoating of virus and release of the genome in the cytoplasm.« less

Challenges to the implementation of International Health Regulations (2005) on preventing infectious diseases: experience from Julius Nyerere International Airport, Tanzania.

PubMed

Bakari, Edith; Frumence, Gasto

2013-08-16

The International Health Regulations (IHR) (2005) is a legal instrument binding all World Health Organization (WHO) member States. It aims to prevent and control public health emergencies of international concern. Country points of entry (POEs) have been identified as potential areas for effective interventions to prevent the transmission of infectious diseases across borders. The agreement postulates that member states will strengthen core capacities detailed in the IHR (2005), including those specified for the POE. This study intended to assess the challenges faced in implementing the IHR (2005) requirements at Julius Nyerere International Airport (JNIA), Dar es Salaam. A cross-sectional, descriptive study, employing qualitative methods, was conducted at the Ministry of Health and Social Welfare (MoHSW), WHO, and JNIA. In-depth interviews, focus group discussions (FGDs) and documentary reviews were used to obtain relevant information. Respondents were purposively enrolled into the study. Thematic analysis was used to generate study findings. Several challenges that hamper implementation of the IHR (2005) were identified: (1) none of the 42 Tanzanian POEs have been specifically designated to implement IHR (2005). (2) Implementation of the IHR (2005) at the POE was complicated as it falls under various uncoordinated government departments. Although there were clear communication channels at JNIA that enhanced reliable risk communication, the airport lacked isolated rooms specific for emergence preparedness and response to public health events. JNIA is yet to develop adequate core capacities required for implementation of the IHR (2005). There is a need for policy managers to designate JNIA to implement IHR (2005) and ensure that public health policies, legislations, guidelines, and practice at POE are harmonized to improve international travel and trade. Policy makers and implementers should also ensure that implementation of the IHR (2005) follow the policy implementation framework, particularly the contextual interaction theory which calls for the availability of adequate resources (inputs) and well-organized process for the successful implementation of the policy.

Antiviral Activity of Glycyrrhizin against Hepatitis C Virus In Vitro

PubMed Central

Matsumoto, Yoshihiro; Matsuura, Tomokazu; Aoyagi, Haruyo; Matsuda, Mami; Hmwe, Su Su; Date, Tomoko; Watanabe, Noriyuki; Watashi, Koichi; Suzuki, Ryosuke; Ichinose, Shizuko; Wake, Kenjiro; Suzuki, Tetsuro; Miyamura, Tatsuo; Wakita, Takaji; Aizaki, Hideki

2013-01-01

Glycyrrhizin (GL) has been used in Japan to treat patients with chronic viral hepatitis, as an anti-inflammatory drug to reduce serum alanine aminotransferase levels. GL is also known to exhibit various biological activities, including anti-viral effects, but the anti-hepatitis C virus (HCV) effect of GL remains to be clarified. In this study, we demonstrated that GL treatment of HCV-infected Huh7 cells caused a reduction of infectious HCV production using cell culture-produced HCV (HCVcc). To determine the target step in the HCV lifecycle of GL, we used HCV pseudoparticles (HCVpp), replicon, and HCVcc systems. Significant suppressions of viral entry and replication steps were not observed. Interestingly, extracellular infectivity was decreased, and intracellular infectivity was increased. By immunofluorescence and electron microscopic analysis of GL treated cells, HCV core antigens and electron-dense particles had accumulated on endoplasmic reticulum attached to lipid droplet (LD), respectively, which is thought to act as platforms for HCV assembly. Furthermore, the amount of HCV core antigen in LD fraction increased. Taken together, these results suggest that GL inhibits release of infectious HCV particles. GL is known to have an inhibitory effect on phospholipase A2 (PLA2). We found that group 1B PLA2 (PLA2G1B) inhibitor also decreased HCV release, suggesting that suppression of virus release by GL treatment may be due to its inhibitory effect on PLA2G1B. Finally, we demonstrated that combination treatment with GL augmented IFN-induced reduction of virus in the HCVcc system. GL is identified as a novel anti-HCV agent that targets infectious virus particle release. PMID:23874843

Reservoir host competence and the role of domestic and commensal hosts in the transmission of Trypanosoma cruzi.

PubMed

Gürtler, Ricardo E; Cardinal, M V

2015-11-01

We review the epidemiological role of domestic and commensal hosts of Trypanosoma cruzi using a quantitative approach, and compiled >400 reports on their natural infection. We link the theory underlying simple mathematical models of vector-borne parasite transmission to the types of evidence used for reservoir host identification: mean duration of infectious life; host infection and infectiousness; and host-vector contact. The infectiousness of dogs or cats most frequently exceeded that of humans. The host-feeding patterns of major vectors showed wide variability among and within triatomine species related to their opportunistic behavior and variable ecological, biological and social contexts. The evidence shows that dogs, cats, commensal rodents and domesticated guinea pigs are able to maintain T. cruzi in the absence of any other host species. They play key roles as amplifying hosts and sources of T. cruzi in many (peri)domestic transmission cycles covering a broad diversity of ecoregions, ecotopes and triatomine species: no other domestic animal plays that role. Dogs comply with the desirable attributes of natural sentinels and sometimes were a point of entry of sylvatic parasite strains. The controversies on the role of cats and other hosts illustrate the issues that hamper assessing the relative importance of reservoir hosts on the basis of fragmentary evidence. We provide various study cases of how eco-epidemiological and genetic-marker evidence helped to unravel transmission cycles and identify the implicated hosts. Keeping dogs, cats and rodents out of human sleeping quarters and reducing their exposure to triatomine bugs are predicted to strongly reduce transmission risks. Copyright © 2015. Published by Elsevier B.V.

Apolipoprotein B100 is required for hepatitis C infectivity and Mipomersen inhibits hepatitis C.

PubMed

Schaefer, Esperance A K; Meixiong, James; Mark, Christina; Deik, Amy; Motola, Daniel L; Fusco, Dahlene; Yang, Andrew; Brisac, Cynthia; Salloum, Shadi; Lin, Wenyu; Clish, Clary B; Peng, Lee F; Chung, Raymond T

2016-12-07

To characterize the role of apolipoprotein B100 (apoB100) in hepatitis C viral (HCV) infection. In this study, we utilize a gene editing tool, transcription activator-like effector nucleases (TALENs), to generate human hepatoma cells with a stable genetic deletion of APOB to assess of apoB in HCV. Using infectious cell culture-competent HCV, viral pseudoparticles, replicon models, and lipidomic analysis we determined the contribution of apoB to each step of the viral lifecycle. We further studied the effect of mipomersen, an FDA-approved antisense inhibitor of apoB100, on HCV using in vitro cell-culture competent HCV and determined its impact on viral infectivity with the TCID50 method. We found that apoB100 is indispensable for HCV infection. Using the JFH-1 fully infectious cell-culture competent virus in Huh 7 hepatoma cells with TALEN-mediated gene deletion of apoB ( APOB KO ), we found a significant reduction in HCV RNA and protein levels following infection. Pseudoparticle and replicon models demonstrated that apoB did not play a role in HCV entry or replication. However, the virus produced by APOB KO cells had significantly diminished infectivity as measured by the TCID-50 method compared to wild-type virus. Lipidomic analysis demonstrated that these virions have a fundamentally altered lipidome, with complete depletion of cholesterol esters. We further demonstrate that inhibition of apoB using mipomersen, an FDA-approved anti-sense oligonucleotide, results in a potent anti-HCV effect and significantly reduces the infectivity of the virus. ApoB is required for the generation of fully infectious HCV virions, and inhibition of apoB with mipomersen blocks HCV. Targeting lipid metabolic pathways to impair viral infectivity represents a novel host targeted strategy to inhibit HCV.

Dysfunction of Bovine Endogenous Retrovirus K2 Envelope Glycoprotein Is Related to Unsuccessful Intracellular Trafficking

PubMed Central

2014-01-01

ABSTRACT Endogenous retroviruses (ERVs) are the remnants of retroviral infection of ancestral germ cells. Mutations introduced into ERVs halt the production of infectious agents, but their effects on the function of retroviral proteins are not fully understood. Retroviral envelope glycoproteins (Envs) are utilized in membrane fusion during viral entry, and we recently identified intact coding sequences for bovine endogenous retrovirus K1 (BERV-K1) and BERV-K2 Envs. Amino acid sequences of BERV-K1 Env (also called Fematrin-1) and BERV-K2 Env are similar, and both viruses are classified in the genus Betaretrovirus. While Fematrin-1 plays an important role in cell-to-cell fusion in bovine placenta, the BERV-K2 envelope gene is marginally expressed in vivo, and its recombinant Env protein is defective in membrane fusion due to inefficient cleavage of surface (SU) and transmembrane subunits. Here, we conducted chimeric analyses of Fematrin-1 and BERV-K2 Envs and revealed that defective maturation of BERV-K2 Env contributed to failed intracellular trafficking. Fluorescence microscopy and flow cytometric analysis suggested that in contrast to Fematrin-1 Env, BERV-K2 Env could not be transported from the endoplasmic reticulum to the trans-Golgi network, where cellular proteases required for processing retroviral Envs are localized. We also identified that one of the responsive regions of this phenomenon resided within a 65-amino-acid region of BERV-K2 SU. This is the first report to identify that retroviral Env SU is involved in the regulation of intracellular trafficking, and it may help to elucidate the maturation process of Fematrin-1 and other related Envs. IMPORTANCE Retroviruses utilize envelope glycoproteins (Envs) to enter host target cells. Mature retroviral Env is a heterodimer, which consists of surface (SU) and transmembrane (TM) subunits that are generated by the cleavage of an Env precursor protein in the trans-Golgi network. SU and TM mediate the recognition of the entry receptor and virus-host membrane fusion, respectively. However, unexplained issues remain for the maturation process of retroviral Env. We previously reported that bovine endogenous retrovirus K2 (BERV-K2) Env lost fusogenicity due to a defect in the cleavage of SU and TM. In this study, we identified that mutations residing in BERV-K2 SU disturbed intracellular trafficking of BERV-K2 Env and resulted its inefficient cleavage. Because SU is not known to play an important role in this process, our study may provide novel insights into the maturation mechanism of retroviral Envs. PMID:24696495

Capsid protein VP4 of human rhinovirus induces membrane permeability by the formation of a size-selective multimeric pore.

PubMed

Panjwani, Anusha; Strauss, Mike; Gold, Sarah; Wenham, Hannah; Jackson, Terry; Chou, James J; Rowlands, David J; Stonehouse, Nicola J; Hogle, James M; Tuthill, Tobias J

2014-08-01

Non-enveloped viruses must deliver their viral genome across a cell membrane without the advantage of membrane fusion. The mechanisms used to achieve this remain poorly understood. Human rhinovirus, a frequent cause of the common cold, is a non-enveloped virus of the picornavirus family, which includes other significant pathogens such as poliovirus and foot-and-mouth disease virus. During picornavirus cell entry, the small myristoylated capsid protein VP4 is released from the virus, interacts with the cell membrane and is implicated in the delivery of the viral RNA genome into the cytoplasm to initiate replication. In this study, we have produced recombinant C-terminal histidine-tagged human rhinovirus VP4 and shown it can induce membrane permeability in liposome model membranes. Dextran size-exclusion studies, chemical crosslinking and electron microscopy demonstrated that VP4 forms a multimeric membrane pore, with a channel size consistent with transfer of the single-stranded RNA genome. The membrane permeability induced by recombinant VP4 was influenced by pH and was comparable to permeability induced by infectious virions. These findings present a molecular mechanism for the involvement of VP4 in cell entry and provide a model system which will facilitate exploration of VP4 as a novel antiviral target for the picornavirus family.

Teaching Critical Thinking in the Business Mathematics Course.

ERIC Educational Resources Information Center

Rosenbaum, Roberta

1986-01-01

Appropriate strategies for teaching students to interpret and understand quantitative data in marketing, management, accounting, and data processing are described. Accompanying figures illustrate samples of percentage markups, trade discounts, gross earning, gross commissions, accounting entries, balance sheet entries, and percentage problems. (CT)

Dynamics of Chikungunya Virus Cell Entry Unraveled by Single-Virus Tracking in Living Cells.

PubMed

Hoornweg, Tabitha E; van Duijl-Richter, Mareike K S; Ayala Nuñez, Nilda V; Albulescu, Irina C; van Hemert, Martijn J; Smit, Jolanda M

2016-05-01

Chikungunya virus (CHIKV) is a rapidly emerging mosquito-borne human pathogen causing major outbreaks in Africa, Asia, and the Americas. The cell entry pathway hijacked by CHIKV to infect a cell has been studied previously using inhibitory compounds. There has been some debate on the mechanism by which CHIKV enters the cell: several studies suggest that CHIKV enters via clathrin-mediated endocytosis, while others show that it enters independently of clathrin. Here we applied live-cell microscopy and monitored the cell entry behavior of single CHIKV particles in living cells transfected with fluorescent marker proteins. This approach allowed us to obtain detailed insight into the dynamic events that occur during CHIKV entry. We observed that almost all particles fused within 20 min after addition to the cells. Of the particles that fused, the vast majority first colocalized with clathrin. The average time from initial colocalization with clathrin to the moment of membrane fusion was 1.7 min, highlighting the rapidity of the cell entry process of CHIKV. Furthermore, these results show that the virus spends a relatively long time searching for a receptor. Membrane fusion was observed predominantly from within Rab5-positive endosomes and often occurred within 40 s after delivery to endosomes. Furthermore, we confirmed that a valine at position 226 of the E1 protein enhances the cholesterol-dependent membrane fusion properties of CHIKV. To conclude, our work confirms that CHIKV enters cells via clathrin-mediated endocytosis and shows that fusion occurs from within acidic early endosomes. Since its reemergence in 2004, chikungunya virus (CHIKV) has spread rapidly around the world, leading to millions of infections. CHIKV often causes chikungunya fever, a self-limiting febrile illness with severe arthralgia. Currently, no vaccine or specific antiviral treatment against CHIKV is available. A potential antiviral strategy is to interfere with the cell entry process of the virus. However, conflicting results with regard to the cell entry pathway used by CHIKV have been published. Here we applied a novel technology to visualize the entry behavior of single CHIKV particles in living cells. Our results show that CHIKV cell entry is extremely rapid and occurs via clathrin-mediated endocytosis. Membrane fusion from within acidic early endosomes is observed. Furthermore, the membrane fusion capacity of CHIKV is strongly promoted by cholesterol in the target membrane. Taking these findings together, this study provides detailed insight into the cell entry process of CHIKV. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Using natural language processing to analyze physician modifications to data entry templates.

PubMed Central

Wilcox, Adam B.; Narus, Scott P.; Bowes, Watson A.

2002-01-01

Efficient data entry by clinicians remains a significant challenge for electronic medical records. Current approaches have largely focused on either structured data entry, which can be limiting in expressive power, or free-text entry, which restricts the use of the data for automated decision support. Text-based templates are a semi-structured data entry method that has been used to assist physicians in manually entering clinical notes, by allowing them to edit predefined example notes. We analyzed changes made to 18,726 sentences from text templates, using a natural language processor. The most common changes were addition or deletion of normal observations, or changes in certainty. We identified common modifications that could be captured in structured form by a graphical user interface. PMID:12463955

The NIAID Radiation Countermeasures Program Business Model

PubMed Central

Hafer, Nathaniel; Maidment, Bert W.

2010-01-01

The National Institute of Allergy and Infectious Diseases (NIAID) Radiation/Nuclear Medical Countermeasures Development Program has developed an integrated approach to providing the resources and expertise required for the research, discovery, and development of radiation/nuclear medical countermeasures (MCMs). These resources and services lower the opportunity costs and reduce the barriers to entry for companies interested in working in this area and accelerate translational progress by providing goal-oriented stewardship of promising projects. In many ways, the radiation countermeasures program functions as a “virtual pharmaceutical firm,” coordinating the early and mid-stage development of a wide array of radiation/nuclear MCMs. This commentary describes the radiation countermeasures program and discusses a novel business model that has facilitated product development partnerships between the federal government and academic investigators and biopharmaceutical companies. PMID:21142762

Protective Microbiota: From Localized to Long-Reaching Co-Immunity

PubMed Central

Chiu, Lynn; Bazin, Thomas; Truchetet, Marie-Elise; Schaeverbeke, Thierry; Delhaes, Laurence; Pradeu, Thomas

2017-01-01

Resident microbiota do not just shape host immunity, they can also contribute to host protection against pathogens and infectious diseases. Previous reviews of the protective roles of the microbiota have focused exclusively on colonization resistance localized within a microenvironment. This review shows that the protection against pathogens also involves the mitigation of pathogenic impact without eliminating the pathogens (i.e., “disease tolerance”) and the containment of microorganisms to prevent pathogenic spread. Protective microorganisms can have an impact beyond their niche, interfering with the entry, establishment, growth, and spread of pathogenic microorganisms. More fundamentally, we propose a series of conceptual clarifications in support of the idea of a “co-immunity,” where an organism is protected by both its own immune system and components of its microbiota. PMID:29270167

Mapping the evolutionary trajectories of morbilliviruses: what, where and whither.

PubMed

Nambulli, Sham; Sharp, Claire R; Acciardo, Andrew S; Drexler, J Felix; Duprex, W Paul

2016-02-01

Morbilliviruses are pathogens of humans and other animals. Live attenuated morbillivirus vaccines have been used to end endemic transmission of measles virus (MV) in many parts of the developed world and to eradicate rinderpest virus. Entry is mediated by two different receptors which govern virus lymphotropism and epitheliotropism. Morbillivirus transmissibility is unparalleled and MV represents the most infectious human pathogen on earth. Their evolutionary origins remain obscure and their potential for adaption to new hosts is poorly understood. It has been suggested that MV could be eradicated. Therefore it is imperative to dissect barriers which restrict cross species infections. This is important as ecological studies identify novel morbilliviruses in a vast number of small mammals and carnivorous predators. Copyright © 2016 Elsevier B.V. All rights reserved.

HIV and travel.

PubMed

Schuhwerk, M A; Richens, J; Zuckerman, Jane N

2006-01-01

There is a high demand for travel among HIV-positive individual. This demand arises partly from those who have benefited from advances in antiretroviral therapy as well as those with disease progression. The key to a successful and uneventful holiday lies in careful pre-trip planning, yet many patients fail to obtain advice before travelling. Travel advice for HIV patients is becoming increasingly specialized. In addition to advice on common travel-related infectious diseases, HIV-positive travellers are strongly advised to carry information with them and they need specific advice regarding country entry restrictions, HIV inclusive travel insurance, safety of travel vaccinations and highly active antiretroviral therapy-related issues. A wide range of relevant issues for the HIV-positive traveller are discussed in this review and useful websites can be found at the end.

Antibiotic resistance of microorganisms in agricultural soils in Russia

NASA Astrophysics Data System (ADS)

Danilova, N. V.; Galitskaya, P. Yu; Selivanovskaya, S. Yu

2018-01-01

Antibiotics are medicines that are widely used in livestock production not only for the prevention and treatment of infectious diseases, but also for accelerating the growth of animals. The application of manure for fertilizing agricultural soils leads to the entry into the soil ecosystem not only of the antibiotics themselves, but also the resistance genes to them. In this study, 30 samples of arable soils were tested for the presence of the tet(X) gene, which encodes bacterial resistance to antibiotics of the tetracycline group. Using real-time PCR, it was found that 27 out of 30 soil samples contained tet(X). 52% of these samples were heavily contaminated, 34% had a medium level of contamination and 14% were slightly contaminated by the resistance gene tet(X).

The NIAID Radiation Countermeasures Program business model.

PubMed

Hafer, Nathaniel; Maidment, Bert W; Hatchett, Richard J

2010-12-01

The National Institute of Allergy and Infectious Diseases (NIAID) Radiation/Nuclear Medical Countermeasures Development Program has developed an integrated approach to providing the resources and expertise required for the research, discovery, and development of radiation/nuclear medical countermeasures (MCMs). These resources and services lower the opportunity costs and reduce the barriers to entry for companies interested in working in this area and accelerate translational progress by providing goal-oriented stewardship of promising projects. In many ways, the radiation countermeasures program functions as a "virtual pharmaceutical firm," coordinating the early and mid-stage development of a wide array of radiation/nuclear MCMs. This commentary describes the radiation countermeasures program and discusses a novel business model that has facilitated product development partnerships between the federal government and academic investigators and biopharmaceutical companies.

Usage of heparan sulfate, integrins, and FAK in HPV16 infection

PubMed Central

Abban, Cynthia Y.; Meneses, Patricio I.

2010-01-01

Human Papillomavirus Type 16 (HPV16) is the major causative agent of cervical cancer. Studies regarding the early binding and signaling molecules that play a significant role in infection are still lacking. The current study analyses the role of heparan sulfate, integrins, and the signaling molecule FAK in HPV16 infection of human adult keratinocytes cell line (HaCaTs). Our data demonstrate that infection requires the binding of viral particles to heparan sulfate followed by activation of focal adhesion kinase through an integrin. Infections were reduced in the presence of the FAK inhibitor, TAE226. TAE226 was observed to inhibit viral entry to the early endosome a known infectious route. These findings suggest that FAK can serve as a novel target for antiviral therapy. PMID:20441998

Biosafety considerations for attenuated measles virus vectors used in virotherapy and vaccination

PubMed Central

Baldo, Aline; Galanis, Evanthia; Tangy, Frédéric; Herman, Philippe

2016-01-01

ABSTRACT Attenuated measles virus (MV) is one of the most effective and safe vaccines available, making it attractive candidate vector to prevent infectious diseases. Attenuated MV have acquired the ability to use the complement regulator CD46 as a major receptor to mediate virus entry and intercellular fusion. Therefore, attenuated MV strains preferentially infect and destroy a wide variety of cancer cells making them also attractive oncolytic vectors. The use of recombinant MV vector has to comply with various regulatory requirements, particularly relating to the assessment of potential risks for human health and the environment. The present article highlights the main characteristics of MV and recombinant MV vectors used for vaccination and virotherapy and discusses these features from a biosafety point of view. PMID:26631840

Alphavirus entry into host cells.

PubMed

Vancini, Ricardo; Hernandez, Raquel; Brown, Dennis

2015-01-01

Viruses have evolved to exploit the vast complexity of cellular processes for their success within the host cell. The entry mechanisms of enveloped viruses (viruses with a surrounding outer lipid bilayer membrane) are usually classified as being either endocytotic or fusogenic. Different mechanisms have been proposed for Alphavirus entry and genome delivery. Indirect observations led to a general belief that enveloped viruses can infect cells either by protein-assisted fusion with the plasma membrane in a pH-independent manner or by endocytosis and fusion with the endocytic vacuole in a low-pH environment. The mechanism of Alphavirus penetration has been recently revisited using direct observation of the processes by electron microscopy under conditions of different temperatures and time progression. Under conditions nonpermissive for endocytosis or any vesicular transport, events occur which allow the entry of the virus genome into the cells. When drug inhibitors of cellular functions are used to prevent entry, only ionophores are found to significantly inhibit RNA delivery. Arboviruses are agents of significant human and animal disease; therefore, strategies to control infections are needed and include development of compounds which will block critical steps in the early infection events. It appears that current evidence points to an entry mechanism, in which alphaviruses infect cells by direct penetration of cell plasma membranes through a pore structure formed by virus and, possibly, host proteins. © 2015 Elsevier Inc. All rights reserved.

Bayesian inference for an emerging arboreal epidemic in the presence of control

PubMed Central

Parry, Matthew; Gibson, Gavin J.; Parnell, Stephen; Gottwald, Tim R.; Irey, Michael S.; Gast, Timothy C.; Gilligan, Christopher A.

2014-01-01

The spread of Huanglongbing through citrus groves is used as a case study for modeling an emerging epidemic in the presence of a control. Specifically, the spread of the disease is modeled as a susceptible-exposed-infectious-detected-removed epidemic, where the exposure and infectious times are not observed, detection times are censored, removal times are known, and the disease is spreading through a heterogeneous host population with trees of different age and susceptibility. We show that it is possible to characterize the disease transmission process under these conditions. Two innovations in our work are (i) accounting for control measures via time dependence of the infectious process and (ii) including seasonal and host age effects in the model of the latent period. By estimating parameters in different subregions of a large commercially cultivated orchard, we establish a temporal pattern of invasion, host age dependence of the dispersal parameters, and a close to linear relationship between primary and secondary infectious rates. The model can be used to simulate Huanglongbing epidemics to assess economic costs and potential benefits of putative control scenarios. PMID:24711393

Systematic review of electronic surveillance of infectious diseases with emphasis on antimicrobial resistance surveillance in resource-limited settings.

PubMed

Rattanaumpawan, Pinyo; Boonyasiri, Adhiratha; Vong, Sirenda; Thamlikitkul, Visanu

2018-02-01

Electronic surveillance of infectious diseases involves rapidly collecting, collating, and analyzing vast amounts of data from interrelated multiple databases. Although many developed countries have invested in electronic surveillance for infectious diseases, the system still presents a challenge for resource-limited health care settings. We conducted a systematic review by performing a comprehensive literature search on MEDLINE (January 2000-December 2015) to identify studies relevant to electronic surveillance of infectious diseases. Study characteristics and results were extracted and systematically reviewed by 3 infectious disease physicians. A total of 110 studies were included. Most surveillance systems were developed and implemented in high-income countries; less than one-quarter were conducted in low-or middle-income countries. Information technologies can be used to facilitate the process of obtaining laboratory, clinical, and pharmacologic data for the surveillance of infectious diseases, including antimicrobial resistance (AMR) infections. These novel systems require greater resources; however, we found that using electronic surveillance systems could result in shorter times to detect targeted infectious diseases and improvement of data collection. This study highlights a lack of resources in areas where an effective, rapid surveillance system is most needed. The availability of information technology for the electronic surveillance of infectious diseases, including AMR infections, will facilitate the prevention and containment of such emerging infectious diseases. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Deburring: an annotated bibliography. Volume VI

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

Gillespie, L.K.

1980-07-01

An annotated summary of 138 articles and publications on burrs, burr prevention and deburring is presented. Thirty-seven deburring processes are listed. Entries cited include English, Russian, French, Japanese, and German language articles. Entries are indexed by deburring processes, author, and language. Indexes also indicate which references discuss equipment and tooling, how to use a proces economics, burr properties, and how to design to minimize burr problems. Research studies are identified as are the materials deburred.

Primary biliary acids inhibit hepatitis D virus (HDV) entry into human hepatoma cells expressing the sodium-taurocholate cotransporting polypeptide (NTCP).

PubMed

Veloso Alves Pereira, Isabel; Buchmann, Bettina; Sandmann, Lisa; Sprinzl, Kathrin; Schlaphoff, Verena; Döhner, Katinka; Vondran, Florian; Sarrazin, Christoph; Manns, Michael P; Pinto Marques Souza de Oliveira, Cláudia; Sodeik, Beate; Ciesek, Sandra; von Hahn, Thomas

2015-01-01

The sodium-taurocholate cotransporting polypeptide (NTCP) is both a key bile acid (BA) transporter mediating uptake of BA into hepatocytes and an essential receptor for hepatitis B virus (HBV) and hepatitis D virus (HDV). In this study we aimed to characterize to what extent and through what mechanism BA affect HDV cell entry. HuH-7 cells stably expressing NTCP (HuH-7/NTCP) and primary human hepatocytes (PHH) were infected with in vitro generated HDV particles. Infectivity in the absence or presence of compounds was assessed using immunofluorescence staining for HDV antigen, standard 50% tissue culture infectious dose (TCID50) assays and quantitative PCR. Addition of primary conjugated and unconjugated BA resulted in a dose dependent reduction in the number of infected cells while secondary, tertiary and synthetic BA had a lesser effect. This effect was observed both in HuH-7/NTCP and in PHH. Other replication cycle steps such as replication and particle assembly and release were unaffected. Moreover, inhibitory BA competed with a fragment from the large HBV envelope protein for binding to NTCP-expressing cells. Conversely, the sodium/BA-cotransporter function of NTCP seemed not to be required for HDV infection since infection was similar in the presence or absence of a sodium gradient across the plasma membrane. When chenodeoxycolic acid (15 mg per kg body weight) was administered to three chronically HDV infected individuals over a period of up to 16 days there was no change in serum HDV RNA. Primary BA inhibit NTCP-mediated HDV entry into hepatocytes suggesting that modulation of the BA pool may affect HDV infection of hepatocytes.

19 CFR 143.44 - RLF procedure.

Code of Federal Regulations, 2010 CFR

2010-04-01

... transmission of invoice data. For RLF transactions, a customs broker or importer of record must transmit electronically, using EIP, any invoice data required by CBP. (b) Electronic transmission of payment. For RLF...) Automation requirements. Only those entries and entry summaries that CBP processes completely in an...

SCOPE in Cataloguing.

ERIC Educational Resources Information Center

Tom, Ellen; Reed, Sue

This report describes the Systematic Computerized Processing in Cataloguing system (SCOPE), an automated system for the catalog department of a university library. The system produces spine labels, pocket labels, book cards for the circulation system, catalog cards including shelf list, main entry, subject and added entry cards, statistics, an…

Timing is everything: Fine-tuned molecular machines orchestrate paramyxovirus entry.

PubMed

Bose, Sayantan; Jardetzky, Theodore S; Lamb, Robert A

2015-05-01

The Paramyxoviridae include some of the great and ubiquitous disease-causing viruses of humans and animals. In most paramyxoviruses, two viral membrane glycoproteins, fusion protein (F) and receptor binding protein (HN, H or G) mediate a concerted process of recognition of host cell surface molecules followed by fusion of viral and cellular membranes, resulting in viral nucleocapsid entry into the cytoplasm. The interactions between the F and HN, H or G viral glycoproteins and host molecules are critical in determining host range, virulence and spread of these viruses. Recently, atomic structures, together with biochemical and biophysical studies, have provided major insights into how these two viral glycoproteins successfully interact with host receptors on cellular membranes and initiate the membrane fusion process to gain entry into cells. These studies highlight the conserved core mechanisms of paramyxovirus entry that provide the fundamental basis for rational anti-viral drug design and vaccine development. Copyright © 2015 Elsevier Inc. All rights reserved.

Paramyxovirus Fusion and Entry: Multiple Paths to a Common End

PubMed Central

Chang, Andres; Dutch, Rebecca E.

2012-01-01

The paramyxovirus family contains many common human pathogenic viruses, including measles, mumps, the parainfluenza viruses, respiratory syncytial virus, human metapneumovirus, and the zoonotic henipaviruses, Hendra and Nipah. While the expression of a type 1 fusion protein and a type 2 attachment protein is common to all paramyxoviruses, there is considerable variation in viral attachment, the activation and triggering of the fusion protein, and the process of viral entry. In this review, we discuss recent advances in the understanding of paramyxovirus F protein-mediated membrane fusion, an essential process in viral infectivity. We also review the role of the other surface glycoproteins in receptor binding and viral entry, and the implications for viral infection. Throughout, we concentrate on the commonalities and differences in fusion triggering and viral entry among the members of the family. Finally, we highlight key unanswered questions and how further studies can identify novel targets for the development of therapeutic treatments against these human pathogens. PMID:22590688

Atomic and molecular data for spacecraft re-entry plasmas

NASA Astrophysics Data System (ADS)

Celiberto, R.; Armenise, I.; Cacciatore, M.; Capitelli, M.; Esposito, F.; Gamallo, P.; Janev, R. K.; Laganà, A.; Laporta, V.; Laricchiuta, A.; Lombardi, A.; Rutigliano, M.; Sayós, R.; Tennyson, J.; Wadehra, J. M.

2016-06-01

The modeling of atmospheric gas, interacting with the space vehicles in re-entry conditions in planetary exploration missions, requires a large set of scattering data for all those elementary processes occurring in the system. A fundamental aspect of re-entry problems is represented by the strong non-equilibrium conditions met in the atmospheric plasma close to the surface of the thermal shield, where numerous interconnected relaxation processes determine the evolution of the gaseous system towards equilibrium conditions. A central role is played by the vibrational exchanges of energy, so that collisional processes involving vibrationally excited molecules assume a particular importance. In the present paper, theoretical calculations of complete sets of vibrationally state-resolved cross sections and rate coefficients are reviewed, focusing on the relevant classes of collisional processes: resonant and non-resonant electron-impact excitation of molecules, atom-diatom and molecule-molecule collisions as well as gas-surface interaction. In particular, collisional processes involving atomic and molecular species, relevant to Earth (N2, O2, NO), Mars (CO2, CO, N2) and Jupiter (H2, He) atmospheres are considered.

The Prion Concept and Synthetic Prions.

PubMed

Legname, Giuseppe; Moda, Fabio

2017-01-01

Transmissible spongiform encephalopathies or prion diseases are a group of fatal neurodegenerative diseases caused by unconventional infectious agents, known as prions (PrP Sc ). Prions derive from a conformational conversion of the normally folded prion protein (PrP C ), which acquires pathological and infectious features. Moreover, PrP Sc is able to transmit the pathological conformation to PrP C through a mechanism that is still not well understood. The generation of synthetic prions, which behave like natural prions, is of fundamental importance to study the process of PrP C conversion and to assess the efficacy of therapeutic strategies to interfere with this process. Moreover, the ability of synthetic prions to induce pathology in animals confirms that the pathological properties of the prion strains are all enciphered in abnormal conformations, characterizing these infectious agents. © 2017 Elsevier Inc. All rights reserved.

US FDA review and regulation of preventive vaccines for infectious disease indications: impact of the FDA Amendments Act 2007.

PubMed

Gruber, Marion F

2011-07-01

Vaccines for prevention or treatment of infectious diseases are biological products that are regulated by the Office of Vaccines Research and Review in the Center for Biologics Evaluation and Research of the US FDA. The legal framework for the regulation of vaccines derives primarily from Section 351 of the Public Health Service Act and from certain sections of the Federal Food, Drug and Cosmetic Act (FFD & C Act). The FDA Amendments Act of 2007 (FDAAA 2007) includes extensive modifications to the FFD & C Act. This article provides an overview of the review process for preventive vaccines and highlights applicable statutory provisions. In addition, this article will discuss changes in the pre-and post-licensure evaluation process for preventive and therapeutic infectious disease vaccines since implementation of the FDAAA 2007.

Characteristics of Coupled Nongray Radiating Gas Flows with Ablation Product Effects About Blunt Bodies During Planetary Entries. Ph.D. Thesis - North Carolina State Univ.

NASA Technical Reports Server (NTRS)

Sutton, K.

1973-01-01

A computational method was developed for the fully-coupled solution of nongray, radiating gas flows with ablation product effects about blunt bodies during planetary entries. The treatment of radiation accounts for molecular band, continuum, and atomic line transitions with a detailed frequency dependence of the absorption coefficient. The ablation of the entry body was solved as part of the solution for a steady-state ablation process. The method was applied by results at typical conditions during entry to Venus. The radiative heating rates along the downstream region of the body can exceed the stagnation point value. The radiative heating to the body is attenuated in the boundary layer at the downstream region of the body and at the stagnation point of the body. A study of the radiation, inviscid flow about spherically capped, conical bodies during planetary entries shows that the nondimensional, radiative heating distributions are nonsimilar with entry conditions. Caution should be exercised in attempting to extrapolate results from known distributions to other entry conditions for which solutions have not yet been obtained.

Semantic Feature Distinctiveness and Frequency

ERIC Educational Resources Information Center

Lamb, Katherine M.

2012-01-01

Lexical access is the process in which basic components of meaning in language, the lexical entries (words) are activated. This activation is based on the organization and representational structure of the lexical entries. Semantic features of words, which are the prominent semantic characteristics of a word concept, provide important information…

7 CFR 1530.110 - Records, certification, and documentation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... SERVICE, DEPARTMENT OF AGRICULTURE THE REFINED SUGAR RE-EXPORT PROGRAM, THE SUGAR CONTAINING PRODUCTS RE... documents to substantiate entries, transfers, exports, or use as appropriate. The Licensing Authority shall...; (3) Include all U.S. Customs forms submitted in the entry or export process; (4) Provide the correct...

7 CFR 1530.110 - Records, certification, and documentation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... SERVICE, DEPARTMENT OF AGRICULTURE THE REFINED SUGAR RE-EXPORT PROGRAM, THE SUGAR CONTAINING PRODUCTS RE... documents to substantiate entries, transfers, exports, or use as appropriate. The Licensing Authority shall...; (3) Include all U.S. Customs forms submitted in the entry or export process; (4) Provide the correct...

7 CFR 1530.110 - Records, certification, and documentation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... SERVICE, DEPARTMENT OF AGRICULTURE THE REFINED SUGAR RE-EXPORT PROGRAM, THE SUGAR CONTAINING PRODUCTS RE... documents to substantiate entries, transfers, exports, or use as appropriate. The Licensing Authority shall...; (3) Include all U.S. Customs forms submitted in the entry or export process; (4) Provide the correct...

7 CFR 1530.110 - Records, certification, and documentation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... SERVICE, DEPARTMENT OF AGRICULTURE THE REFINED SUGAR RE-EXPORT PROGRAM, THE SUGAR CONTAINING PRODUCTS RE... documents to substantiate entries, transfers, exports, or use as appropriate. The Licensing Authority shall...; (3) Include all U.S. Customs forms submitted in the entry or export process; (4) Provide the correct...

78 FR 40531 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing of a Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-05

... Exchange from allowing re-entry into the Program where the Exchange deems such re-entry as proper. CLP... its status as a CLP, such Member may re- apply for CLP status. Such application process shall occur at...

7 CFR 1530.110 - Records, certification, and documentation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... SERVICE, DEPARTMENT OF AGRICULTURE THE REFINED SUGAR RE-EXPORT PROGRAM, THE SUGAR CONTAINING PRODUCTS RE... documents to substantiate entries, transfers, exports, or use as appropriate. The Licensing Authority shall...; (3) Include all U.S. Customs forms submitted in the entry or export process; (4) Provide the correct...

Dynamic Oligomerization of Integrase Orchestrates HIV Nuclear Entry.

PubMed

Borrenberghs, Doortje; Dirix, Lieve; De Wit, Flore; Rocha, Susana; Blokken, Jolien; De Houwer, Stéphanie; Gijsbers, Rik; Christ, Frauke; Hofkens, Johan; Hendrix, Jelle; Debyser, Zeger

2016-11-10

Nuclear entry is a selective, dynamic process granting the HIV-1 pre-integration complex (PIC) access to the chromatin. Classical analysis of nuclear entry of heterogeneous viral particles only yields averaged information. We now have employed single-virus fluorescence methods to follow the fate of single viral pre-integration complexes (PICs) during infection by visualizing HIV-1 integrase (IN). Nuclear entry is associated with a reduction in the number of IN molecules in the complexes while the interaction with LEDGF/p75 enhances IN oligomerization in the nucleus. Addition of LEDGINs, small molecule inhibitors of the IN-LEDGF/p75 interaction, during virus production, prematurely stabilizes a higher-order IN multimeric state, resulting in stable IN multimers resistant to a reduction in IN content and defective for nuclear entry. This suggests that a stringent size restriction determines nuclear pore entry. Taken together, this work demonstrates the power of single-virus imaging providing crucial insights in HIV replication and enabling mechanism-of-action studies.

Infectious disease burden and cognitive function in young to middle-aged adults.

PubMed

Gale, Shawn D; Erickson, Lance D; Berrett, Andrew; Brown, Bruce L; Hedges, Dawson W

2016-02-01

Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults. Copyright © 2015 Elsevier Inc. All rights reserved.

[Proteomics in infectious diseases].

PubMed

Quero, Sara; Párraga-Niño, Noemí; García-Núñez, Marian; Sabrià, Miquel

2016-04-01

Infectious diseases have a high incidence in the population, causing a major impact on global health. In vitro culture of microorganisms is the first technique applied for infection diagnosis which is laborious and time consuming. In recent decades, efforts have been focused on the applicability of "Omics" sciences, highlighting the progress provided by proteomic techniques in the field of infectious diseases. This review describes the management, processing and analysis of biological samples for proteomic research. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Illuminating the landscape of host–pathogen interactions with the bacterium Listeria monocytogenes

PubMed Central

Cossart, Pascale

2011-01-01

Listeria monocytogenes has, in 25 y, become a model in infection biology. Through the analysis of both its saprophytic life and infectious process, new concepts in microbiology, cell biology, and pathogenesis have been discovered. This review will update our knowledge on this intracellular pathogen and highlight the most recent breakthroughs. Promising areas of investigation such as the increasingly recognized relevance for the infectious process, of RNA-mediated regulations in the bacterium, and the role of bacterially controlled posttranslational and epigenetic modifications in the host will also be discussed. PMID:22114192

19 CFR 163.11 - Audit procedures.

Code of Federal Regulations, 2014 CFR

2014-04-01

... how the results of the sampling will be projected over the universe of transactions for purposes of... results over the universe of transactions is the process by which the results obtained from the sample entries actually examined are applied to the universe of entries set within the time period and scope of...

19 CFR 163.11 - Audit procedures.

Code of Federal Regulations, 2012 CFR

2012-04-01

... how the results of the sampling will be projected over the universe of transactions for purposes of... results over the universe of transactions is the process by which the results obtained from the sample entries actually examined are applied to the universe of entries set within the time period and scope of...

19 CFR 163.11 - Audit procedures.

Code of Federal Regulations, 2013 CFR

2013-04-01

... how the results of the sampling will be projected over the universe of transactions for purposes of... results over the universe of transactions is the process by which the results obtained from the sample entries actually examined are applied to the universe of entries set within the time period and scope of...

Think Exit at Entry

ERIC Educational Resources Information Center

O'Rourke, Tom; Satterfield, Coy E.

2005-01-01

This paper describes the "Think Exit at Entry" program that has become the guiding principle for the Georgia Department of Juvenile Justice (DJJ). The Georgia DJJ believes that the transition process begins the day the youth enters the system and continues well after release from the institution. Literature points the need for transition…

How the Admission Criteria to a Competitive-Entry Undergraduate Programme Could Be Improved

ERIC Educational Resources Information Center

Shulruf, Boaz; Shaw, John

2015-01-01

The introduction of a new standards-based secondary school assessment system, the National Certificate of Educational Achievement (NCEA), necessitated significant changes to the admissions processes for New Zealand universities, particularly for competitive-entry programmes such as medicine, engineering and pharmacy. Selection to such programmes…

Implementation of home-based medication order entry at a community hospital.

PubMed

Thorne, Alicia; Williamson, Sarah; Jellison, Tara; Jellison, Chris

2009-11-01

The implementation of a home-based order-entry program at a community hospital is described. Parkview Hospital is a 600-bed, community-based facility located in Fort Wayne, Indiana, that provides 24-hour pharmacy services. The main purpose for establishing a home-based order-entry program was to provide extra pharmacist coverage during the event of a spontaneous order surge in an effort to maintain excellent customer service. A virtual private network (VPN) was created to ensure the security and confidentiality of patients' health care information. The names of volunteer pharmacists who met specific criteria and who were capable of performing home-based order entry were collected. These pharmacists were trained and tested in the home-based order-entry process. When home-based order-entry is needed, the lead pharmacist contacts the pharmacists on the list by telephone. If available, the pharmacists (maximum of three) are notified to log into the Internet, access the VPN, and perform order entry with the same vigilance, confidentiality, and care as they would onsite. Home-based order entry is discontinued when off-trigger points are met. Pharmacists entering orders from home are paid by the time spent conducting order entry. Pharmacists reported that the program was easy to contact home-based order-entry volunteers, there were no problems with logging into the VPNs, and turnaround time was close to our target of 25 minutes. A community-based hospital successfully implemented a home-based medication order-entry program. The program alleviated the shortage of pharmacists during spontaneous surges of medication orders.

Modelling the effect of urbanization on the transmission of an infectious disease.

PubMed

Zhang, Ping; Atkinson, Peter M

2008-01-01

This paper models the impact of urbanization on infectious disease transmission by integrating a CA land use development model, population projection matrix model and CA epidemic model in S-Plus. The innovative feature of this model lies in both its explicit treatment of spatial land use development, demographic changes, infectious disease transmission and their combination in a dynamic, stochastic model. Heuristically-defined transition rules in cellular automata (CA) were used to capture the processes of both land use development with urban sprawl and infectious disease transmission. A population surface model and dwelling distribution surface were used to bridge the gap between urbanization and infectious disease transmission. A case study is presented involving modelling influenza transmission in Southampton, a dynamically evolving city in the UK. The simulation results for Southampton over a 30-year period show that the pattern of the average number of infection cases per day can depend on land use and demographic changes. The modelling framework presents a useful tool that may be of use in planning applications.

Simulations for designing and interpreting intervention trials in infectious diseases.

PubMed

Halloran, M Elizabeth; Auranen, Kari; Baird, Sarah; Basta, Nicole E; Bellan, Steven E; Brookmeyer, Ron; Cooper, Ben S; DeGruttola, Victor; Hughes, James P; Lessler, Justin; Lofgren, Eric T; Longini, Ira M; Onnela, Jukka-Pekka; Özler, Berk; Seage, George R; Smith, Thomas A; Vespignani, Alessandro; Vynnycky, Emilia; Lipsitch, Marc

2017-12-29

Interventions in infectious diseases can have both direct effects on individuals who receive the intervention as well as indirect effects in the population. In addition, intervention combinations can have complex interactions at the population level, which are often difficult to adequately assess with standard study designs and analytical methods. Herein, we urge the adoption of a new paradigm for the design and interpretation of intervention trials in infectious diseases, particularly with regard to emerging infectious diseases, one that more accurately reflects the dynamics of the transmission process. In an increasingly complex world, simulations can explicitly represent transmission dynamics, which are critical for proper trial design and interpretation. Certain ethical aspects of a trial can also be quantified using simulations. Further, after a trial has been conducted, simulations can be used to explore the possible explanations for the observed effects. Much is to be gained through a multidisciplinary approach that builds collaborations among experts in infectious disease dynamics, epidemiology, statistical science, economics, simulation methods, and the conduct of clinical trials.

Ablation and Chemical Alteration of Cosmic Dust Particles during Entry into the Earth’s Atmosphere

NASA Astrophysics Data System (ADS)

Rudraswami, N. G.; Shyam Prasad, M.; Dey, S.; Plane, J. M. C.; Feng, W.; Carrillo-Sánchez, J. D.; Fernandes, D.

2016-12-01

Most dust-sized cosmic particles undergo ablation and chemical alteration during atmospheric entry, which alters their original properties. A comprehensive understanding of this process is essential in order to decipher their pre-entry characteristics. The purpose of the study is to illustrate the process of vaporization of different elements for various entry parameters. The numerical results for particles of various sizes and various zenith angles are treated in order to understand the changes in chemical composition that the particles undergo as they enter the atmosphere. Particles with large sizes (> few hundred μm) and high entry velocities (>16 km s‑1) experience less time at peak temperatures compared to those that have lower velocities. Model calculations suggest that particles can survive with an entry velocity of 11 km s‑1 and zenith angles (ZA) of 30°–90°, which accounts for ∼66% of the region where particles retain their identities. Our results suggest that the changes in chemical composition of MgO, SiO2, and FeO are not significant for an entry velocity of 11 km s‑1 and sizes <300 μm, but the changes in these compositions become significant beyond this size, where FeO is lost to a major extent. However, at 16 km s‑1 the changes in MgO, SiO2, and FeO are very intense, which is also reflected in Mg/Si, Fe/Si, Ca/Si, and Al/Si ratios, even for particles with a size of 100 μm. Beyond 400 μm particle sizes at 16 km s‑1, most of the major elements are vaporized, leaving the refractory elements, Al and Ca, suspended in the troposphere.

CPOE in Iran--a viable prospect? Physicians' opinions on using CPOE in an Iranian teaching hospital.

PubMed

Kazemi, Alireza; Ellenius, Johan; Tofighi, Shahram; Salehi, Aref; Eghbalian, Fatemeh; Fors, Uno G

2009-03-01

In recent years, the theory that on-line clinical decision support systems can improve patients' safety among hospitalised individuals has gained greater acceptance. However, the feasibility of implementing such a system in a middle or low-income country has rarely been studied. Understanding the current prescription process and a proper needs assessment of prescribers can act as the key to successful implementation. The aim of this study was to explore physicians' opinions on the current prescription process, and the expected benefits and perceived obstacles to employ Computerised Physician Order Entry in an Iranian teaching hospital. Initially, the interview guideline was developed through focus group discussions with eight experts. Then semi-structured interviews were held with 19 prescribers. After verbatim transcription, inductive thematic analysis was performed on empirical data. Forty hours of on-looker observations were performed in different wards to explore the current prescription process. The current prescription process was identified as a physician-centred, top-down, model, where prescribers were found to mostly rely on their memories as well as being overconfident. Some errors may occur during different paper-based registrations, transcriptions and transfers. Physician opinions on Computerised Physician Order Entry were categorised into expected benefits and perceived obstacles. Confidentiality issues, reduction of medication errors and educational benefits were identified as three themes in the expected benefits category. High cost, social and cultural barriers, data entry time and problems with technical support emerged as four themes in the perceived obstacles category. The current prescription process has a high possibility of medication errors. Although there are different barriers confronting the implementation and continuation of Computerised Physician Order Entry in Iranian hospitals, physicians have a willingness to use them if these systems provide significant benefits. A pilot study in a limited setting and a comprehensive analysis of health outcomes and economic indicators should be performed, to assess the merits of introducing Computerised Physician Order Entry with decision support capabilities in Iran.

Entry inhibitors: New advances in HCV treatment

PubMed Central

Qian, Xi-Jing; Zhu, Yong-Zhe; Zhao, Ping; Qi, Zhong-Tian

2016-01-01

Hepatitis C virus (HCV) infection affects approximately 3% of the world's population and causes chronic liver diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. Although current antiviral therapy comprising direct-acting antivirals (DAAs) can achieve a quite satisfying sustained virological response (SVR) rate, it is still limited by viral resistance, long treatment duration, combined adverse reactions, and high costs. Moreover, the currently marketed antivirals fail to prevent graft reinfections in HCV patients who receive liver transplantations, probably due to the cell-to-cell transmission of the virus, which is also one of the main reasons behind treatment failure. HCV entry is a highly orchestrated process involving initial attachment and binding, post-binding interactions with host cell factors, internalization, and fusion between the virion and the host cell membrane. Together, these processes provide multiple novel and promising targets for antiviral therapy. Most entry inhibitors target host cell components with high genetic barriers and eliminate viral infection from the very beginning of the viral life cycle. In future, the addition of entry inhibitors to a combination of treatment regimens might optimize and widen the prevention and treatment of HCV infection. This review summarizes the molecular mechanisms and prospects of the current preclinical and clinical development of antiviral agents targeting HCV entry. PMID:26733381

1984 Bibliography of atomic and molecular processes

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

Barnett, C.F.; Gilbody, H.B.; Gregory, D.C.

1985-04-01

This annotated bibliography includes papers on atomic and molecular processes published during 1984. Sources include scientific journals, conference proceedings, and books. Each entry is designated by one or more of the 114 categories of atomic and molecular processes used by the Controlled Fusion Atomic Data Center, Oak Ridge National Laboratory to classify data. Also indicated is whether the work was experimental or theoretical, what energy range was covered, what reactants were investigated, and the country of origin of the first author. Following the bibliographical listing, the entries are indexed according to the categories and according to reactants within each subcategory.

1982 bibliography of atomic and molecular processes

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

Barnett, C.F.; Crandall, D.H.; Gilbody, H.B.

1984-05-01

This annotated bibliography includes papers on atomic and molecular processes published during 1982. Sources include scientific journals, conference proceedings, and books. Each entry is designated by one or more of the 114 categories of atomic and molecular processes used by the Controlled Fusion Atomic Data Center, Oak Ridge National Laboratory to classify data. Also indicated is whether the work was experimental or theoretical, what energy range was covered, what reactants were investigated, and the country of origin of the first author. Following the bibliographical listing, the entries are indexed according to the categories and according to reactants within each subcategory.

Common Variable Immunodeficiency Non-Infectious Disease Endotypes Redefined Using Unbiased Network Clustering in Large Electronic Datasets.

PubMed

Farmer, Jocelyn R; Ong, Mei-Sing; Barmettler, Sara; Yonker, Lael M; Fuleihan, Ramsay; Sullivan, Kathleen E; Cunningham-Rundles, Charlotte; Walter, Jolan E

2017-01-01

Common variable immunodeficiency (CVID) is increasingly recognized for its association with autoimmune and inflammatory complications. Despite recent advances in immunophenotypic and genetic discovery, clinical care of CVID remains limited by our inability to accurately model risk for non-infectious disease development. Herein, we demonstrate the utility of unbiased network clustering as a novel method to analyze inter-relationships between non-infectious disease outcomes in CVID using databases at the United States Immunodeficiency Network (USIDNET), the centralized immunodeficiency registry of the United States, and Partners, a tertiary care network in Boston, MA, USA, with a shared electronic medical record amenable to natural language processing. Immunophenotypes were comparable in terms of native antibody deficiencies, low titer response to pneumococcus, and B cell maturation arrest. However, recorded non-infectious disease outcomes were more substantial in the Partners cohort across the spectrum of lymphoproliferation, cytopenias, autoimmunity, atopy, and malignancy. Using unbiased network clustering to analyze 34 non-infectious disease outcomes in the Partners cohort, we further identified unique patterns of lymphoproliferative (two clusters), autoimmune (two clusters), and atopic (one cluster) disease that were defined as CVID non-infectious endotypes according to discrete and non-overlapping immunophenotypes. Markers were both previously described {high serum IgE in the atopic cluster [odds ratio (OR) 6.5] and low class-switched memory B cells in the total lymphoproliferative cluster (OR 9.2)} and novel [low serum C3 in the total lymphoproliferative cluster (OR 5.1)]. Mortality risk in the Partners cohort was significantly associated with individual non-infectious disease outcomes as well as lymphoproliferative cluster 2, specifically (OR 5.9). In contrast, unbiased network clustering failed to associate known comorbidities in the adult USIDNET cohort. Together, these data suggest that unbiased network clustering can be used in CVID to redefine non-infectious disease inter-relationships; however, applicability may be limited to datasets well annotated through mechanisms such as natural language processing. The lymphoproliferative, autoimmune, and atopic Partners CVID endotypes herein described can be used moving forward to streamline genetic and biomarker discovery and to facilitate early screening and intervention in CVID patients at highest risk for autoimmune and inflammatory progression.

Research on the water-entry attitude of a submersible aircraft.

PubMed

Xu, BaoWei; Li, YongLi; Feng, JinFu; Hu, JunHua; Qi, Duo; Yang, Jian

2016-01-01

The water entry of a submersible aircraft, which is transient, highly coupled, and nonlinear, is complicated. After analyzing the mechanics of this process, the change rate of every variable is considered. A dynamic model is build and employed to study vehicle attitude and overturn phenomenon during water entry. Experiments are carried out and a method to organize experiment data is proposed. The accuracy of the method is confirmed by comparing the results of simulation of dynamic model and experiment under the same condition. Based on the analysis of the experiment and simulation, the initial attack angle and angular velocity largely influence the water entry of vehicle. Simulations of water entry with different initial and angular velocities are completed, followed by an analysis, and the motion law of vehicle is obtained. To solve the problem of vehicle stability and control during water entry, an approach is proposed by which the vehicle sails with a zero attack angle after entering water by controlling the initial angular velocity. With the dynamic model and optimization research algorithm, calculation is performed, and the optimal initial angular velocity of water-entry is obtained. The outcome of simulations confirms that the effectiveness of the propose approach by which the initial water-entry angular velocity is controlled.

Multiple oxygen entry pathways in globin proteins revealed by intrinsic pathway identification method

NASA Astrophysics Data System (ADS)

Takayanagi, Masayoshi; Kurisaki, Ikuo; Nagaoka, Masataka

2015-12-01

Each subunit of human hemoglobin (HbA) stores an oxygen molecule (O2) in the binding site (BS) cavity near the heme group. The BS is buried in the interior of the subunit so that there is a debate over the O2 entry pathways from solvent to the BS; histidine gate or multiple pathways. To elucidate the O2 entry pathways, we executed ensemble molecular dynamics (MD) simulations of T-state tetramer HbA in high concentration O2 solvent to simulate spontaneous O2 entry from solvent into the BS. By analyzing 128 independent 8 ns MD trajectories by intrinsic pathway identification by clustering (IPIC) method, we found 141 and 425 O2 entry events into the BS of the α and β subunits, respectively. In both subunits, we found that multiple O2 entry pathways through inside cavities play a significant role for O2 entry process of HbA. The rate constants of O2 entry estimated from the MD trajectories correspond to the experimentally observed values. In addition, by analyzing monomer myoglobin, we verified that the high O2 concentration condition can reproduce the ratios of each multiple pathway in the one-tenth lower O2 concentration condition. These indicate the validity of the multiple pathways obtained in our MD simulations.

How do children with a chronic or long-term illness perceive their school re-entry after a period of homebound instruction?

PubMed

Boonen, H; Petry, K

2012-07-01

A considerable number of children are confronted with a chronic or long-term illness in their lives. For these children, absenteeism is problematic, because education plays a major role in stimulating their cognitive development and in promoting a sense of normalcy and psychosocial well-being. In the literature, a great deal of attention has been paid to school reintegration programmes, which try to counter the barriers that these children may face when they return to school. Another way of surmounting these barriers is through the use of homebound instruction, in which the educational process for the child is continued during the period of absence. Despite the growing awareness of the necessity of education for these children, there is still little empirical research available addressing programmes that facilitate school re-entry. The major goal of this study is to investigate how parents and their children with a chronic or long-term illness perceive school re-entry after a period of homebound instruction, by using a descriptive-explorative, multi-informant research design. Participants were 60 children and their parents who filled in a self-constructed questionnaire. Both parents and children perceived the period of homebound instruction, as well as their school re-entry, predominantly positively. Most of the children stated that they had been able to keep up with their subjects, and that they had good contact with their peers when they returned to school. According to parents, homebound instruction made a positive contribution to the school re-entry of their child. The current study is one of the first to explore the school re-entry of children with a chronic or long-term illness. According to both parents and children, the school re-entry process passed off positively. However, more research is needed with regard to the quality of education and the programmes aimed at facilitating school re-entry. © 2011 Blackwell Publishing Ltd.

Determinants in the Ig Variable Domain of Human HAVCR1 (TIM-1) Are Required To Enhance Hepatitis C Virus Entry.

PubMed

Kachko, Alla; Costafreda, Maria Isabel; Zubkova, Iryna; Jacques, Jerome; Takeda, Kazuyo; Wells, Frances; Kaplan, Gerardo; Major, Marian E

2018-03-15

Hepatitis C virus (HCV) is the leading cause of chronic hepatitis in humans. Several host molecules participate in HCV cell entry, but this process remains unclear. The complete unraveling of the HCV entry process is important to further understand viral pathogenesis and develop therapeutics. Human hepatitis A virus (HAV) cellular receptor 1 (HAVCR1), CD365, also known as TIM-1, functions as a phospholipid receptor involved in cell entry of several enveloped viruses. Here, we studied the role of HAVCR1 in HCV infection. HAVCR1 antibody inhibited entry in a dose-dependent manner. HAVCR1 soluble constructs neutralized HCV, which did not require the HAVCR1 mucinlike region and was abrogated by a mutation of N to A at position 94 (N94A) in the Ig variable (IgV) domain phospholipid-binding pocket, indicating a direct interaction of the HAVCR1 IgV domain with HCV virions. However, knockout of HAVCR1 in Huh7 cells reduced but did not prevent HCV growth. Interestingly, the mouse HAVCR1 ortholog, also a phospholipid receptor, did not enhance infection and a soluble form failed to neutralize HCV, although replacement of the mouse IgV domain with the human HAVCR1 IgV domain restored the enhancement of HCV infection. Mutations in the cytoplasmic tail revealed that direct HAVCR1 signaling is not required to enhance HCV infection. Our data show that the phospholipid-binding function and other determinant(s) in the IgV domain of human HAVCR1 enhance HCV infection. Although the exact mechanism is not known, it is possible that HAVCR1 facilitates entry by stabilizing or enhancing attachment, leading to direct interactions with specific receptors, such as CD81. IMPORTANCE Hepatitis C virus (HCV) enters cells through a multifaceted process. We identified the human hepatitis A virus cellular receptor 1 (HAVCR1), CD365, also known as TIM-1, as a facilitator of HCV entry. Antibody blocking and silencing or knockout of HAVCR1 in hepatoma cells reduced HCV entry. Our findings that the interaction of HAVCR1 with HCV early during infection enhances entry but is not required for infection support the hypothesis that HAVCR1 facilitates entry by stabilizing or enhancing virus binding to the cell surface membrane and allowing the correct virus-receptor positioning for interaction with the main HCV receptors. Furthermore, our data show that in addition to the phospholipid-binding function of HAVCR1, the enhancement of HCV infection involves other determinants in the IgV domain of HAVCR1. These findings expand the repertoire of molecules that HCV uses for cell entry, adding to the already complex mechanism of HCV infection and pathogenesis. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

Substitution at aspartic acid 1128 in the SARS coronavirus spike glycoprotein mediates escape from a S2 domain-targeting neutralizing monoclonal antibody.

PubMed

Ng, Oi-Wing; Keng, Choong-Tat; Leung, Cynthia Sau-Wai; Peiris, J S Malik; Poon, Leo Lit Man; Tan, Yee-Joo

2014-01-01

The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is the etiological agent for the infectious disease, SARS, which first emerged 10 years ago. SARS-CoV is a zoonotic virus that has crossed the species barriers to infect humans. Bats, which harbour a diverse pool of SARS-like CoVs (SL-CoVs), are believed to be the natural reservoir. The SARS-CoV surface Spike (S) protein is a major antigenic determinant in eliciting neutralizing antibody production during SARS-CoV infection. In our previous work, we showed that a panel of murine monoclonal antibodies (mAbs) that target the S2 subunit of the S protein are capable of neutralizing SARS-CoV infection in vitro (Lip KM et al, J Virol. 2006 Jan; 80(2): 941-50). In this study, we report our findings on the characterization of one of these mAbs, known as 1A9, which binds to the S protein at a novel epitope within the S2 subunit at amino acids 1111-1130. MAb 1A9 is a broadly neutralizing mAb that prevents viral entry mediated by the S proteins of human and civet SARS-CoVs as well as bat SL-CoVs. By generating mutant SARS-CoV that escapes the neutralization by mAb 1A9, the residue D1128 in S was found to be crucial for its interaction with mAb 1A9. S protein containing the substitution of D1128 with alanine (D1128A) exhibited a significant decrease in binding capability to mAb 1A9 compared to wild-type S protein. By using a pseudotyped viral entry assay, it was shown that the D1128A substitution in the escape virus allows it to overcome the viral entry blockage by mAb 1A9. In addition, the D1128A mutation was found to exert no effects on the S protein cell surface expression and incorporation into virion particles, suggesting that the escape virus retains the same viral entry property as the wild-type virus.

Does Antibiotic Treatment Affect the Diagnostic Accuracy of 18F-FDG PET/CT Studies in Patients with Suspected Infectious Processes?

PubMed

Kagna, Olga; Kurash, Marina; Ghanem-Zoubi, Nesrin; Keidar, Zohar; Israel, Ora

2017-11-01

18 F-FDG PET/CT plays a significant role in the assessment of various infectious processes. Patients with suspected or known sites of infection are often referred for 18 F-FDG imaging while already receiving antibiotic treatment. The current study assessed whether antibiotic therapy affected the detectability rate of infectious processes by 18 F-FDG PET/CT. Methods: A 5-y retrospective study of all adult patients who underwent 18 F-FDG PET/CT in search of a focal source of infection was performed. The presence, duration, and appropriateness of antibiotic treatment before 18 F-FDG imaging were recorded. Diagnosis of an infectious process was based on microbiologic or pathologic data as well as on clinical and radiologic follow-up. Results: Two hundred seventeen patients underwent 243 PET/CT studies in search of a focal source of infection and were included in the study. Sixty-seven studies were excluded from further analysis because of a final noninfectious etiology or lack of further follow-up or details regarding the antibiotic treatment. The final study population included 176 18 F-FDG PET/CT studies in 153 patients (107 men, 46 women; age range, 18-86 y). One hundred nineteen studies (68%) were performed in patients receiving antibiotic therapy for a range of 1-73 d. A diagnosis of infection was made in 107 true-positive cases (61%), including 63 studies (59%) in patients receiving appropriate antibiotic therapy started before the performance of the 18 F-FDG PET/CT study. There were 52 true-negative (29%) and 17 false-positive (10%) 18 F-FDG PET/CT studies. No false-negative results were found. Conclusion: 18 F-FDG PET/CT correctly identified foci of increased uptake compatible with infection in most patients, including all patients receiving appropriate antimicrobial therapy, with no false-negative cases. On the basis of the current study results, the administration of antibiotics appears to have no clinically significant impact on the diagnostic accuracy of 18 F-FDG PET/CT performed for evaluation of known or suspected infectious processes. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Human parainfluenza virus type 3 (HPIV-3); Construction and rescue of an infectious, recombinant virus expressing the enhanced green fluorescent protein (EGFP).

USDA-ARS?s Scientific Manuscript database

The ability to rescue an infectious, recombinant, RNA virus from a cDNA clone, has led to new opportunities for measuring viral replication from a viral expressed reporter gene. In this protocol, the process of inserting enhanced green fluorescent protein (EGFP) gene into the human parainfluenza vi...

Recommendations for control of pathogens and infectious diseases in fish research facilities☆

PubMed Central

Kent, Michael L.; Feist, Stephen W.; Harper, Claudia; Hoogstraten-Miller, Shelley; Mac Law, J.; Sánchez-Morgado, José M.; Tanguay, Robert L.; Sanders, George E.; Spitsbergen, Jan M.; Whipps, Christopher M.

2012-01-01

Concerns about infectious diseases in fish used for research have risen along with the dramatic increase in the use of fish as models in biomedical research. In addition to acute diseases causing severe morbidity and mortality, underlying chronic conditions that cause low-grade or subclinical infections may confound research results. Here we present recommendations and strategies to avoid or minimize the impacts of infectious agents in fishes maintained in the research setting. There are distinct differences in strategies for control of pathogens in fish used for research compared to fishes reared as pets or in aquaculture. Also, much can be learned from strategies and protocols for control of diseases in rodents used in research, but there are differences. This is due, in part, the unique aquatic environment that is modified by the source and quality of the water provided and the design of facilities. The process of control of pathogens and infectious diseases in fish research facilities is relatively new, and will be an evolving process over time. Nevertheless, the goal of documenting, detecting, and excluding pathogens in fish is just as important as in mammalian research models. PMID:18755294

Recommendations for control of pathogens and infectious diseases in fish research facilities

USGS Publications Warehouse

Kent, M.L.; Feist, S.W.; Harper, C.; Hoogstraten-Miller, S.; Law, J.M.; Sanchez-Morgado, J. M.; Tanguay, R.L.; Sanders, G.E.; Spitsbergen, J.M.; Whipps, Christopher M.

2009-01-01

Concerns about infectious diseases in fish used for research have risen along with the dramatic increase in the use of fish as models in biomedical research. In addition to acute diseases causing severe morbidity and mortality, underlying chronic conditions that cause low-grade or subclinical infections may confound research results. Here we present recommendations and strategies to avoid or minimize the impacts of infectious agents in fishes maintained in the research setting. There are distinct differences in strategies for control of pathogens in fish used for research compared to fishes reared as pets or in aquaculture. Also, much can be learned from strategies and protocols for control of diseases in rodents used in research, but there are differences. This is due, in part, the unique aquatic environment that is modified by the source and quality of the water provided and the design of facilities. The process of control of pathogens and infectious diseases in fish research facilities is relatively new, and will be an evolving process over time. Nevertheless, the goal of documenting, detecting, and excluding pathogens in fish is just as important as in mammalian research models.

Analysis of Mars Pathfinder Entry Data, Aerothermal Heating, and Heat Shield Material Response

NASA Technical Reports Server (NTRS)

Milos, Frank; Chen, Y. K.; Tran, H. K.; Rasky, Daniel J. (Technical Monitor)

1997-01-01

The Mars Pathfinder heatshield contained several thermocouples and resistance thermometers. A description of the experiment, the entry data, and analysis of the entry environment and material response is presented. In particular, the analysis addresses uncertainties of the data and the fluid dynamics and material response models. The calculations use the latest trajectory and atmosphere reconstructions for the Pathfinder entry. A modified version of the GIANTS code is used for CFD (computational fluid dynamics) analyses, and FIAT is used for material response. The material response and flowfield are coupled appropriately. Three different material response models are considered. The analysis of Pathfinder entry data for validation of aerothermal heating and material response models is complicated by model uncertainties and unanticipated data-acquisition and processing problems. We will discuss these issues as well as ramifications of the data and analysis for future Mars missions.

[The electronic health record: computerised provider order entry and the electronic instruction document as new functionalities].

PubMed

Derikx, Joep P M; Erdkamp, Frans L G; Hoofwijk, A G M

2013-01-01

An electronic health record (EHR) should provide 4 key functionalities: (a) documenting patient data; (b) facilitating computerised provider order entry; (c) displaying the results of diagnostic research; and (d) providing support for healthcare providers in the clinical decision-making process.- Computerised provider order entry into the EHR enables the electronic receipt and transfer of orders to ancillary departments, which can take the place of handwritten orders.- By classifying the computer provider order entries according to disorders, digital care pathways can be created. Such care pathways could result in faster and improved diagnostics.- Communicating by means of an electronic instruction document that is linked to a computerised provider order entry facilitates the provision of healthcare in a safer, more efficient and auditable manner.- The implementation of a full-scale EHR has been delayed as a result of economic, technical and legal barriers, as well as some resistance by physicians.

[Teaching infectious diseases in the Medical Degree within the European higher education area].

PubMed

Gutiérrez, Félix; Masiá, Mar

2016-01-01

During their medical studies, students must acquire basic competencies in different areas of knowledge, one of which is infectious diseases. Training in infectious diseases is essential for general medical practice and for academic or professional expertise in many areas of medicine, both medical and surgical. The vast amount of knowledge that is continuously generated about infectious diseases requires a well-structured undergraduate medical education program and framed in a setting dominated by globalization. The incorporation of Spain to the European higher education area has forced medical schools to adapt their curriculum and to establish the content and learning objectives of all courses of study. In this paper, we discuss the implications of the integration of the Spanish university system in the European higher education area («Bologna Process») in the teaching of infectious diseases in the Degree of Medicine, and describe the learning program in infectious diseases of the University Miguel Hernández of Elche (Alicante, Spain) based on learning outcomes and competencies. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Rab5 and Rab11 Are Required for Clathrin-Dependent Endocytosis of Japanese Encephalitis Virus in BHK-21 Cells.

PubMed

Liu, Chun-Chun; Zhang, Yun-Na; Li, Zhao-Yao; Hou, Jin-Xiu; Zhou, Jing; Kan, Lin; Zhou, Bin; Chen, Pu-Yan

2017-10-01

During infection Japanese encephalitis virus (JEV) generally enters host cells via receptor-mediated clathrin-dependent endocytosis. The trafficking of JEV within endosomes is controlled by Rab GTPases, but which Rab proteins are involved in JEV entry into BHK-21 cells is unknown. In this study, entry and postinternalization of JEV were analyzed using biochemical inhibitors, RNA interference, and dominant negative (DN) mutants. Our data demonstrate that JEV entry into BHK-21 cells depends on clathrin, dynamin, and cholesterol but not on caveolae or macropinocytosis. The effect on JEV infection of dominant negative (DN) mutants of four Rab proteins that regulate endosomal trafficking was examined. Expression of DN Rab5 and DN Rab11, but not DN Rab7 and DN Rab9, significantly inhibited JEV replication. These results were further tested by silencing Rab5 or Rab11 expression before viral infection. Confocal microscopy showed that virus particles colocalized with Rab5 or Rab11 within 15 min after virus entry, suggesting that after internalization JEV moves to early and recycling endosomes before the release of the viral genome. Our findings demonstrate the roles of Rab5 and Rab11 on JEV infection of BHK-21 cells through the endocytic pathway, providing new insights into the life cycle of flaviviruses. IMPORTANCE Although Japanese encephalitis virus (JEV) utilizes different endocytic pathways depending on the cell type being infected, the detailed mechanism of its entry into BHK-21 cells is unknown. Understanding the process of JEV endocytosis and postinternalization will advance our knowledge of JEV infection and pathogenesis as well as provide potential novel drug targets for antiviral intervention. With this objective, we used systematic approaches to dissect this process. The results show that entry of JEV into BHK-21 cells requires a low-pH environment and that the process occurs through dynamin-, actin-, and cholesterol-dependent clathrin-mediated endocytosis that requires Rab5 and Rab11. Our work provides a detailed picture of the entry of JEV into BHK-21 cells and the cellular events that follow. Copyright © 2017 American Society for Microbiology.

Mars Science Laboratory Entry, Descent, and Landing Trajectory and Atmosphere Reconstruction

NASA Technical Reports Server (NTRS)

Karlgaard, Christopher D.; Kutty, Prasad; Schoenenberer, Mark; Shidner, Jeremy D.

2013-01-01

On August 5th 2012, The Mars Science Laboratory entry vehicle successfully entered Mars atmosphere and landed the Curiosity rover on its surface. A Kalman filter approach has been implemented to reconstruct the entry, descent, and landing trajectory based on all available data. The data sources considered in the Kalman filtering approach include the inertial measurement unit accelerations and angular rates, the terrain descent sensor, the measured landing site, orbit determination solutions for the initial conditions, and a new set of instrumentation for planetary entry reconstruction consisting of forebody pressure sensors, known as the Mars Entry Atmospheric Data System. These pressure measurements are unique for planetary entry, descent, and landing reconstruction as they enable a reconstruction of the freestream atmospheric conditions without any prior assumptions being made on the vehicle aerodynamics. Moreover, the processing of these pressure measurements in the Kalman filter approach enables the identification of atmospheric winds, which has not been accomplished in past planetary entry reconstructions. This separation of atmosphere and aerodynamics allows for aerodynamic model reconciliation and uncertainty quantification, which directly impacts future missions. This paper describes the mathematical formulation of the Kalman filtering approach, a summary of data sources and preprocessing activities, and results of the reconstruction.

Midwives and the Computerization of Perinatal Data Entry: The Theory of Beneficial Engagement.

PubMed

Craswell, Alison; Moxham, Lorna; Broadbent, Marc

2016-10-01

Theory building in nursing and midwifery both to explain and inform practice is important to advance these professions via provision of a theoretical foundation. This research explored the process of perinatal data entry undertaken by midwives to explore the impact of the movement from paper to computer collection of data. Use of grounded theory methodology enabled theory building, leading to a theoretical understanding of the phenomenon and development of the Theory of Beneficial Engagement grounded in the data. Methods involved in-depth semistructured interviews with 15 users of perinatal data systems. Participants were recruited from 12 different healthcare locations and were utilizing three different electronic systems for data entry. The research question that guided the study focused on examining the influences of using the computer for perinatal data entry. Findings indicated that qualities particular to some midwives denoted engagement with perinatal data entry, suggesting a strong desire to enter complete, timely, and accurate data. The Theory of Beneficial Engagement provides a model of user engagement with systems for perinatal data entry consistent with other theories of engagement. The theory developed describes this phenomenon in a simple, elegant manner that can be applied to other areas where mandatory data entry is undertaken.

Antitubercular nucleosides that inhibit siderophore biosynthesis: SAR of the glycosyl domain.

PubMed

Somu, Ravindranadh V; Wilson, Daniel J; Bennett, Eric M; Boshoff, Helena I; Celia, Laura; Beck, Brian J; Barry, Clifton E; Aldrich, Courtney C

2006-12-28

Tuberculosis is the leading cause of infectious disease mortality in the world by a bacterial pathogen. We previously demonstrated that a bisubstrate inhibitor of the adenylation enzyme MbtA, which is responsible for the second step of mycobactin biosynthesis, exhibited potent antitubercular activity. Here we systematically investigate the structure-activity relationships of the bisubstrate inhibitor glycosyl domain resulting in the identification of a carbocyclic analogue that possesses a KIapp value of 2.3 nM and MIC99 values of 1.56 microM against M. tuberculosis H37Rv. The SAR data suggest the intriguing possibility that the bisubstrate inhibitors utilize a transporter for entry across the mycobacterial cell envelope. Additionally, we report improved conditions for the expression of MbtA and biochemical analysis, demonstrating that MbtA follows a random sequential enzyme mechanism for the adenylation half-reaction.

Flavivirus structural heterogeneity: implications for cell entry.

PubMed

Rey, Félix A; Stiasny, Karin; Heinz, Franz X

2017-06-01

The explosive spread of Zika virus is the most recent example of the threat imposed to human health by flaviviruses. High-resolution structures are available for several of these arthropod-borne viruses, revealing alternative icosahedral organizations of immature and mature virions. Incomplete proteolytic maturation, however, results in a cloud of highly heterogeneous mosaic particles. This heterogeneity is further expanded by a dynamic behavior of the viral envelope glycoproteins. The ensemble of heterogeneous and dynamic infectious particles circulating in infected hosts offers a range of alternative possible receptor interaction sites at their surfaces, potentially contributing to the broad flavivirus host-range and variation in tissue tropism. The potential synergy between heterogeneous particles in the circulating cloud thus provides an additional dimension to understand the unanticipated properties of Zika virus in its recent outbreaks. Copyright © 2017 Elsevier B.V. All rights reserved.

Three Papers in International Health Policy: Modeling the Links between Economics and Epidemiology

DTIC Science & Technology

2008-04-01

acquire  the disease in  community  transmission.  Wu et al. (2006)27 compare the effect on the overall attack rate of  community ‐level policies  that  reduce...waging  containment  battles at airports and high risk  communities  rather than a large‐ scale  mitigation war. This  could be achieved with entry and travel...history:  illness,  recovery,  or  death.  The  response  of  communities   to  infectious  disease  varied  across  cultures and  levels of  scientific

Advances in canine distemper virus pathogenesis research: a wildlife perspective.

PubMed

Loots, Angelika K; Mitchell, Emily; Dalton, Desiré L; Kotzé, Antoinette; Venter, Estelle H

2017-03-01

Canine distemper virus (CDV) has emerged as a significant disease of wildlife, which is highly contagious and readily transmitted between susceptible hosts. Initially described as an infectious disease of domestic dogs, it is now recognized as a global multi-host pathogen, infecting and causing mass mortalities in a wide range of carnivore species. The last decade has seen the effect of numerous CDV outbreaks in various wildlife populations. Prevention of CDV requires a clear understanding of the potential hosts in danger of infection as well as the dynamic pathways CDV uses to gain entry to its host cells and its ability to initiate viral shedding and disease transmission. We review recent research conducted on CDV infections in wildlife, including the latest findings on the causes of host specificity and cellular receptors involved in distemper pathogenesis.

BMC Ecology image competition: the winning images

PubMed Central

2013-01-01

BMC Ecology announces the winning entries in its inaugural Ecology Image Competition, open to anyone affiliated with a research institute. The competition, which received more than 200 entries from international researchers at all career levels and a wide variety of scientific disciplines, was looking for striking visual interpretations of ecological processes. In this Editorial, our academic Section Editors and guest judge Dr Yan Wong explain what they found most appealing about their chosen winning entries, and highlight a few of the outstanding images that didn’t quite make it to the top prize. PMID:23517630

BMC Ecology image competition: the winning images.

PubMed

Harold, Simon; Wong, Yan; Baguette, Michel; Bonsall, Michael B; Clobert, Jean; Royle, Nick J; Settele, Josef

2013-03-22

BMC Ecology announces the winning entries in its inaugural Ecology Image Competition, open to anyone affiliated with a research institute. The competition, which received more than 200 entries from international researchers at all career levels and a wide variety of scientific disciplines, was looking for striking visual interpretations of ecological processes. In this Editorial, our academic Section Editors and guest judge Dr Yan Wong explain what they found most appealing about their chosen winning entries, and highlight a few of the outstanding images that didn't quite make it to the top prize.

Adoption of One Health in Thailand's National strategic plan for emerging infectious diseases.

PubMed

Sommanustweechai, Angkana; Iamsirithaworn, Sopon; Patcharanarumol, Walaiporn; Kalpravidh, Wantanee; Tangcharoensathien, Viroj

2017-02-01

This study illustrates how Thailand adopted the One Health concept. Massive socio-economic and health consequences of emerging infectious diseases, especially Avian Influenza in 2004, led to recognition of the importance of and need for One Health. Based on collaboration and consultative meetings between the national actors and international development partners, Thailand adopted One Health to drive more effective containment of Emerging Infectious Diseases. This concept gained support from the non-governmental and civil society organizations through processes of the National Health Assembly. In 2012, a Cabinet resolution endorsed a National Strategic Plan for Emerging Infectious Diseases (2013-2016), in which One Health appeared as a core principle. Collaboration among multi-disciplinary groups of professionals, particularly epidemiologists trained in Field Epidemiology Training Programs (FETP), including FETP, FETP-veterinarian, and FETP-wildlife veterinarians, promoted implementation of One Health.

76 FR 11199 - Application(s) for Duty-Free Entry of Scientific Instruments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-01

... of the central nervous systems of freshwater prawns. Justification for Duty-Free Entry: There are no... 120 kV accelerating voltage, and an electron gun assembly with Cool Beam Illumination System--LaB6..., flexibility of software for signal acquisition and image processing, overall system stability, and ease of use...

Education for Perspective Transformation. Women's Re-entry Programs in Community Colleges.

ERIC Educational Resources Information Center

Mezirow, Jack; Marsick, Victoria

The national field study of women's re-entry programs in community colleges reported here was done to identify factors that impeded or facilitated the progress of these programs. After an introduction, the content is presented in three sections. The first section deals with perspective transformation, the adult development process occurring in the…

19 CFR 210.30 - Requests for production of documents and things and entry upon land.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false Requests for production of documents and things and entry upon land. 210.30 Section 210.30 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Discovery and Compulsory Process...

40 CFR 63.3176 - What definitions apply to this subpart?

Code of Federal Regulations, 2011 CFR

2011-07-01

... automobiles or light-duty trucks, including coating facilities and processes. Bake oven air seal means an entry or entry vestibule to or an exit or exit vestibule from a bake oven which isolates the bake oven... exit or exit vestibule) the bake oven. No significant VOC generating activity takes place in a bake...

Web-Based Time Entry Systems: Providing Greater Automation and Compliance

ERIC Educational Resources Information Center

Williams, Tracy

2005-01-01

Time and resources are becoming increasingly scarce in most higher education institutions today. As a result, colleges and universities are looking to streamline and simplify many costly, labor-intensive administrative processes. In this article, Tracy Williams examines how Web-based time-entry systems can help institutions save valuable time and…

Predictors of Student Success in Entry-Level Science Courses

ERIC Educational Resources Information Center

Singh, Mamta K.

2009-01-01

Although the educational evaluation process is useful and valuable and is supported by the Higher Education Act, a strong research base for program evaluation of college entry-level science courses is still lacking. Studies in science disciplines such as, biology, chemistry, and physics have addressed various affective and demographic factors and…

Water-use computer programs for Florida

USGS Publications Warehouse

Geiger, L.H.

1984-01-01

Using U.S. Geological Survey computer programs L149-L153, this report shows how to process water-use data for the functional water-use categories: public supply, rural supply, industrial self-supplied, irrigation, and thermo-electric power generation. The programs are used to selectively retrieve entries and list them in a format suitable for publication. Instructions are given for coding cards to produce tables of water-use data for each of the functional use categories. These cards contain entries that identify a particular water-use data-collection site in Florida. Entries on the cards include location information such as county code, water management district code, hydrologic unit code, and, where applicable, a site name and number. Annual and monthly pumpage is included. These entries are shown with several different headings; for example, surface water or ground water, freshwater or saline pumpages, or consumptive use. All the programs use a similar approach; however, the actual programs differ with each functional water-use category and are discussed separately. Data prepared for these programs can also be processed by the National Water-Use Data System. (USGS)

Differential virulence mechanisms of infectious hematopoietic necrosis virus in rainbow trout (Oncorhynchus mykiss) include host entry and virus replication kinetics

USGS Publications Warehouse

Penaranda, M.M.D.; Purcell, M.K.; Kurath, G.

2009-01-01

Host specificity is a phenomenon exhibited by all viruses. For the fish rhabdovirus infectious hematopoietic necrosis virus (IHNV), differential specificity of virus strains from the U and M genogroups has been established both in the field and in experimental challenges. In rainbow trout (Oncorhynchus mykiss), M IHNV strains are consistently more prevalent and more virulent than U IHNV. The basis of the differential ability of these two IHNV genogroups to cause disease in rainbow trout was investigated in live infection challenges with representative U and M IHNV strains. When IHNV was delivered by intraperitoneal injection, the mortality caused by U IHNV increased, indicating that the low virulence of U IHNV is partly due to inefficiency in entering the trout host. Analyses of in vivo replication showed that U IHNV consistently had lower prevalence and lower viral load than M IHNV during the course of infection. In analyses of the host immune response, M IHNV-infected fish consistently had higher and longer expression of innate immune-related genes such as Mx-1. This suggests that the higher virulence of M IHNV is not due to suppression of the immune response in rainbow trout. Taken together, the results support a kinetics hypothesis wherein faster replication enables M IHNV to rapidly achieve a threshold level of virus necessary to override the strong host innate immune response. ?? 2009 SGM.

Incidence of rash after amoxicillin treatment in children with infectious mononucleosis.

PubMed

Chovel-Sella, Aluma; Ben Tov, Amir; Lahav, Einat; Mor, Orna; Rudich, Hagit; Paret, Gideon; Reif, Shimon

2013-05-01

"Ampicillin rash," a phenomenon unique to patients with Epstein-Barr virus acute infectious mononucleosis (AIM) treated with ampicillin, was first reported in the 1960s. The incidence was estimated as being between 80% and 100%, and the figures have not been reviewed since those first accounts. We sought to establish the current incidence of rash associated with antibiotic treatment among children with AIM. A retrospective study of all hospitalized children diagnosed as having AIM based upon positive Epstein-Barr virus serology in 2 pediatric tertiary medical centers in Israel. Of the 238 children who met the study entry criteria during the study period, 173 were treated with antibiotics. Fifty-seven (32.9%) of the subjects treated with antibiotics had a rash during their illness compared with 15 (23.1%) in untreated patients (P = .156; not significant). Amoxicillin was associated with the highest incidence of antibiotic-induced rash occurrence (29.5%, 95% confidence interval: 18.52-42.57), but significantly lower than the 90% rate reported for ampicillin in past studies. Age, gender, ethnicity, and atopic or allergic history were not associated with the development of rash after antibiotic exposure. Among the laboratory data, only increased white blood cell counts were more prevalent among subjects who did not develop an antibiotic-induced rash. The incidence of rash in pediatric patients with AIM after treatment with the current oral aminopenicillin (amoxicillin) is much lower than originally reported.

Streptococcal toxic shock syndrome secondary to group A Streptococcus vaginitis.

PubMed

Hikone, Mayu; Kobayashi, Ken-Ichiro; Washino, Takuya; Ota, Masayuki; Sakamoto, Naoya; Iwabuchi, Sentaro; Ohnishi, Kenji

2015-12-01

Streptococcal toxic shock syndrome (TSS) is a systemic illness usually caused in the setting of infection by group A Streptococcus (GAS). The primary infections are often invasive infections of the respiratory tract or necrotizing infections of the skin and soft tissue, but some infections occur without relevant focus. GAS vaginitis is a rare condition among adult women and is accordingly thought to be uncommon as a cause of streptococcal TSS. Here we report the cases of two postmenopausal women with streptococcal TSS secondary to GAS vaginitis, one aged 55 and one aged 60. Both came to our emergency department with complaints or symptoms of abdominal pain, fever, hypotension, and multi-organ failure. In both cases, the relevant factor associated with streptococcal infection was a recent episode of GAS vaginitis. Both underwent fluid management and 14 days of antibiotic treatment and fully recovered without complications. Vaginitis was likely to be the primary infectious trigger of TSS in these two cases. Intrauterine device insertion, endometrial biopsy, and post-partum state have all been previously reported in TSS patients, and the female genital tract has been described as a portal of entry. GAS vaginitis warrants appropriate treatment as it may progress to severe systemic infection as described. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Automatically processed alpha-track radon monitor

DOEpatents

Langner, Jr., G. Harold

1993-01-01

An automatically processed alpha-track radon monitor is provided which includes a housing having an aperture allowing radon entry, and a filter that excludes the entry of radon daughters into the housing. A flexible track registration material is located within the housing that records alpha-particle emissions from the decay of radon and radon daughters inside the housing. The flexible track registration material is capable of being spliced such that the registration material from a plurality of monitors can be spliced into a single strip to facilitate automatic processing of the registration material from the plurality of monitors. A process for the automatic counting of radon registered by a radon monitor is also provided.

Automatically processed alpha-track radon monitor

DOEpatents

Langner, G.H. Jr.

1993-01-12

An automatically processed alpha-track radon monitor is provided which includes a housing having an aperture allowing radon entry, and a filter that excludes the entry of radon daughters into the housing. A flexible track registration material is located within the housing that records alpha-particle emissions from the decay of radon and radon daughters inside the housing. The flexible track registration material is capable of being spliced such that the registration material from a plurality of monitors can be spliced into a single strip to facilitate automatic processing of the registration material from the plurality of monitors. A process for the automatic counting of radon registered by a radon monitor is also provided.

Non-infectious inflammatory genital lesions.

PubMed

Andreassi, Lucio; Bilenchi, Roberta

2014-01-01

The genitalia may be the site of non-infectious inflammatory lesions that are generally manifested as balanoposthitis and vulvovaginitis. In men, these forms constitute 50% of all balanoposthitis forms, and in women, vulvovaginitis frequency is even higher. They consist of genital locations of general skin diseases, such as psoriasis, lichen planus, lichen sclerosus, and other clinical entities with their own physiognomy, such as Zoon's balanitis-vulvitis. Diagnosis of genital non-infectious inflammatory lesions is usually made on clinical criteria. A biopsy is only necessary for the identification of clinical conditions that may simulate inflammatory form but are actually premalignant processes. © 2014 Elsevier Inc. All rights reserved.

MSL EDL Entry Guidance using the Entry Terminal Point Controller

NASA Technical Reports Server (NTRS)

2006-01-01

The Mars Science Laboratory will be the first Mars mission to attempt a guided entry with the objective of safely delivering the entry vehicle to a survivable parachute deploy state within 10 km of the pre-designated landing site. The Entry Terminal Point Controller guidance algorithm is derived from the final phase Apollo Command Module guidance and, like Apollo, modulates the bank angle to control range based on deviations in range, altitude rate, and drag acceleration from a reference trajectory. For application to Mars landers which must make use of the tenuous Martian atmosphere, it is critical to balance the lift of the vehicle to minimize the range while still ensuring a safe deploy altitude. An overview of the process to generate optimized guidance settings is presented, discussing improvements made over the last four years. Performance tradeoffs between ellipse size and deploy altitude will be presented, along with imposed constraints of entry acceleration and heating. Performance sensitivities to the bank reversal deadbands, heading alignment, attitude initialization error, and atmospheric delivery errors are presented. Guidance settings for contingency operations, such as those appropriate for severe dust storm scenarios, are evaluated.

A combination HIV reporter virus system for measuring post-entry event efficiency and viral outcome in primary CD4+ T cell subsets.

PubMed

Tilton, Carisa A; Tabler, Caroline O; Lucera, Mark B; Marek, Samantha L; Haqqani, Aiman A; Tilton, John C

2014-01-01

Fusion between the viral membrane of human immunodeficiency virus (HIV) and the host cell marks the end of the HIV entry process and the beginning of a series of post-entry events including uncoating, reverse transcription, integration, and viral gene expression. The efficiency of post-entry events can be modulated by cellular factors including viral restriction factors and can lead to several distinct outcomes: productive, latent, or abortive infection. Understanding host and viral proteins impacting post-entry event efficiency and viral outcome is critical for strategies to reduce HIV infectivity and to optimize transduction of HIV-based gene therapy vectors. Here, we report a combination reporter virus system measuring both membrane fusion and viral promoter-driven gene expression. This system enables precise determination of unstimulated primary CD4+ T cell subsets targeted by HIV, the efficiency of post-entry viral events, and viral outcome and is compatible with high-throughput screening and cell-sorting methods. Copyright © 2013 Elsevier B.V. All rights reserved.

The process of development of a prioritization tool for a clinical decision support build within a computerized provider order entry system: Experiences from St Luke's Health System.

PubMed

Wolf, Matthew; Miller, Suzanne; DeJong, Doug; House, John A; Dirks, Carl; Beasley, Brent

2016-09-01

To establish a process for the development of a prioritization tool for a clinical decision support build within a computerized provider order entry system and concurrently to prioritize alerts for Saint Luke's Health System. The process of prioritizing clinical decision support alerts included (a) consensus sessions to establish a prioritization process and identify clinical decision support alerts through a modified Delphi process and (b) a clinical decision support survey to validate the results. All members of our health system's physician quality organization, Saint Luke's Care as well as clinicians, administrators, and pharmacy staff throughout Saint Luke's Health System, were invited to participate in this confidential survey. The consensus sessions yielded a prioritization process through alert contextualization and associated Likert-type scales. Utilizing this process, the clinical decision support survey polled the opinions of 850 clinicians with a 64.7 percent response rate. Three of the top rated alerts were approved for the pre-implementation build at Saint Luke's Health System: Acute Myocardial Infarction Core Measure Sets, Deep Vein Thrombosis Prophylaxis within 4 h, and Criteria for Sepsis. This study establishes a process for developing a prioritization tool for a clinical decision support build within a computerized provider order entry system that may be applicable to similar institutions. © The Author(s) 2015.

Core drug-drug interaction alerts for inclusion in pediatric electronic health records with computerized prescriber order entry.

PubMed

Harper, Marvin B; Longhurst, Christopher A; McGuire, Troy L; Tarrago, Rod; Desai, Bimal R; Patterson, Al

2014-03-01

The study aims to develop a core set of pediatric drug-drug interaction (DDI) pairs for which electronic alerts should be presented to prescribers during the ordering process. A clinical decision support working group composed of Children's Hospital Association (CHA) members was developed. CHA Pharmacists and Chief Medical Information Officers participated. Consensus was reached on a core set of 19 DDI pairs that should be presented to pediatric prescribers during the order process. We have provided a core list of 19 high value drug pairs for electronic drug-drug interaction alerts to be recommended for inclusion as high value alerts in prescriber order entry software used with a pediatric patient population. We believe this list represents the most important pediatric drug interactions for practical implementation within computerized prescriber order entry systems.

In Vivo fitness associated with high virulence in a vertebrate virus is a complex trait regulated by host entry, replication, and shedding

USGS Publications Warehouse

Wargo, Andrew R.; Kurath, Gael

2011-01-01

The relationship between pathogen fitness and virulence is typically examined by quantifying only one or two pathogen fitness traits. More specifically, it is regularly assumed that within-host replication, as a precursor to transmission, is the driving force behind virulence. In reality, many traits contribute to pathogen fitness, and each trait could drive the evolution of virulence in different ways. Here, we independently quantified four viral infection cycle traits, namely, host entry, within-host replication, within-host coinfection fitness, and shedding, in vivo, in the vertebrate virus Infectious hematopoietic necrosis virus (IHNV). We examined how each of these stages of the viral infection cycle contributes to the fitness of IHNV genotypes that differ in virulence in rainbow trout. This enabled us to determine how infection cycle fitness traits are independently associated with virulence. We found that viral fitness was independently regulated by each of the traits examined, with the largest impact on fitness being provided by within-host replication. Furthermore, the more virulent of the two genotypes of IHNV we used had advantages in all of the traits quantified. Our results are thus congruent with the assumption that virulence and within-host replication are correlated but suggest that infection cycle fitness is complex and that replication is not the only trait associated with virulence.

FDA-Approved Selective Estrogen Receptor Modulators Inhibit Ebola Virus Infection

PubMed Central

Johansen, Lisa M.; Brannan, Jennifer M.; Delos, Sue E.; Shoemaker, Charles J.; Stossel, Andrea; Lear, Calli; Hoffstrom, Benjamin G.; DeWald, Lisa Evans; Schornberg, Kathryn L.; Scully, Corinne; Lehár, Joseph; Hensley, Lisa E.; White, Judith M.; Olinger, Gene G.

2014-01-01

Ebola viruses remain a substantial threat to both civilian and military populations as bioweapons, during sporadic outbreaks, and from the possibility of accidental importation from endemic regions by infected individuals. Currently, no approved therapeutics exist to treat or prevent infection by Ebola viruses. Therefore, we performed an in vitro screen of Food and Drug Administration (FDA)– and ex–US-approved drugs and selected molecular probes to identify drugs with antiviral activity against the type species Zaire ebolavirus (EBOV). From this screen, we identified a set of selective estrogen receptor modulators (SERMs), including clomiphene and toremifene, which act as potent inhibitors of EBOV infection. Anti-EBOV activity was confirmed for both of these SERMs in an in vivo mouse infection model. This anti-EBOV activity occurred even in the absence of detectable estrogen receptor expression, and both SERMs inhibited virus entry after internalization, suggesting that clomiphene and toremifene are not working through classical pathways associated with the estrogen receptor. Instead, the response appeared to be an off-target effect where the compounds interfere with a step late in viral entry and likely affect the triggering of fusion. These data support the screening of readily available approved drugs to identify therapeutics for the Ebola viruses and other infectious diseases. The SERM compounds described in this report are an immediately actionable class of approved drugs that can be repurposed for treatment of filovirus infections. PMID:23785035

Casualty Handling Simulation Using the Scenario-based Engineering Process

DTIC Science & Technology

2000-02-28

HERPES ZOSTER ENCEPHALITIS HEPATITIS INFECTIOUS VIRAL ANIMAL BITES/RABIES EXPOSURE MUMPS INFECTIOUS MONONUCLEOSIS TRACHOMA STD-SYPHILIS STD...casualties as they flow through the system. Identifying the proper mix is complicated by many factors, including the specific casualty stream, the...casualties as they flow through the system. Identifying the proper mix is complicated by its dependence on mission types. For example, the types and

Comparison of a semi-automatic annotation tool and a natural language processing application for the generation of clinical statement entries.

PubMed

Lin, Ching-Heng; Wu, Nai-Yuan; Lai, Wei-Shao; Liou, Der-Ming

2015-01-01

Electronic medical records with encoded entries should enhance the semantic interoperability of document exchange. However, it remains a challenge to encode the narrative concept and to transform the coded concepts into a standard entry-level document. This study aimed to use a novel approach for the generation of entry-level interoperable clinical documents. Using HL7 clinical document architecture (CDA) as the example, we developed three pipelines to generate entry-level CDA documents. The first approach was a semi-automatic annotation pipeline (SAAP), the second was a natural language processing (NLP) pipeline, and the third merged the above two pipelines. We randomly selected 50 test documents from the i2b2 corpora to evaluate the performance of the three pipelines. The 50 randomly selected test documents contained 9365 words, including 588 Observation terms and 123 Procedure terms. For the Observation terms, the merged pipeline had a significantly higher F-measure than the NLP pipeline (0.89 vs 0.80, p<0.0001), but a similar F-measure to that of the SAAP (0.89 vs 0.87). For the Procedure terms, the F-measure was not significantly different among the three pipelines. The combination of a semi-automatic annotation approach and the NLP application seems to be a solution for generating entry-level interoperable clinical documents. © The Author 2014. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.comFor numbered affiliation see end of article.

Process for hydraulically mining coal. [28 claims

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

Shoji, K.; Sieling, R.E.; Taylor, J.T.

The invention is a method for the hydraulic mining of coal of varying hardness. It is described in particular as to coal of the type occurring in the Balmer seam in British Columbia. By the method at least two parallel spaced entries are driven upward through a seam of coal. Monitors are positioned in each entry. Each monitor is horizontally and vertically pivotable, and has nozzle means from which a jet of water under a pressure of about 1900 to 2200 psi is emitted. The high pressure jet cuts the coal, which is then fed to a machine that breaksmore » and crushes the coal into sizes wherein the resultant coal/water slurry will flow down a sloped flume into a dewatering station. The method further embodies differentially retreating along adjacent parallel entries by increments of desirably at least about 40 feet each. By the different retreat system, as a panel of coal is hydraulically mined in one entry, the monitor and associated equipment in a second adjacent parallel entry are moved back the desired increment to the next working position (retreated). When the panel of coal in the first entry is mined, the monitor is retreated in the same manner and hydraulic mining commences in the second adjacent parallel entry. The operation is thus alternated along the length of the parallel entries. 28 claims, 4 figures.« less

Data-model fusion to better understand emerging pathogens and improve infectious disease forecasting.

PubMed

LaDeau, Shannon L; Glass, Gregory E; Hobbs, N Thompson; Latimer, Andrew; Ostfeld, Richard S

2011-07-01

Ecologists worldwide are challenged to contribute solutions to urgent and pressing environmental problems by forecasting how populations, communities, and ecosystems will respond to global change. Rising to this challenge requires organizing ecological information derived from diverse sources and formally assimilating data with models of ecological processes. The study of infectious disease has depended on strategies for integrating patterns of observed disease incidence with mechanistic process models since John Snow first mapped cholera cases around a London water pump in 1854. Still, zoonotic and vector-borne diseases increasingly affect human populations, and methods used to successfully characterize directly transmitted diseases are often insufficient. We use four case studies to demonstrate that advances in disease forecasting require better understanding of zoonotic host and vector populations, as well of the dynamics that facilitate pathogen amplification and disease spillover into humans. In each case study, this goal is complicated by limited data, spatiotemporal variability in pathogen transmission and impact, and often, insufficient biological understanding. We present a conceptual framework for data-model fusion in infectious disease research that addresses these fundamental challenges using a hierarchical state-space structure to (1) integrate multiple data sources and spatial scales to inform latent parameters, (2) partition uncertainty in process and observation models, and (3) explicitly build upon existing ecological and epidemiological understanding. Given the constraints inherent in the study of infectious disease and the urgent need for progress, fusion of data and expertise via this type of conceptual framework should prove an indispensable tool.

Robust real-time cell analysis method for determining viral infectious titers during development of a viral vaccine production process.

PubMed

Charretier, Cédric; Saulnier, Aure; Benair, Loïc; Armanet, Corinne; Bassard, Isabelle; Daulon, Sandra; Bernigaud, Bertrand; Rodrigues de Sousa, Emanuel; Gonthier, Clémence; Zorn, Edouard; Vetter, Emmanuelle; Saintpierre, Claire; Riou, Patrice; Gaillac, David

2018-02-01

The classical cell-culture methods, such as cell culture infectious dose 50% (CCID 50 ) assays, are time-consuming, end-point assays currently used during the development of a viral vaccine production process to measure viral infectious titers. However, they are not suitable for handling the large number of tests required for high-throughput and large-scale screening analyses. Impedance-based bio-sensing techniques used in real-time cell analysis (RTCA) to assess cell layer biological status in vitro, provide real-time data. In this proof-of-concept study, we assessed the correlation between the results from CCID 50 and RTCA assays and compared time and costs using monovalent and tetravalent chimeric yellow fever dengue (CYD) vaccine strains. For the RTCA assay, Vero cells were infected with the CYD sample and real-time impedance was recorded, using the dimensionless cell index (CI). The CI peaked just after infection and decreased as the viral cytopathic effect occurred in a dose-dependent manner. The time to the median CI (CIT med ) was correlated with viral titers determined by CCID 50 over a range of about 4-5log 10 CCID 50 /ml. This in-house RTCA virus-titration assay was shown to be a robust method for determining real-time viral infectious titers, and could be an alternative to the classical CCID 50 assay during the development of viral vaccine production process. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Impact of the infectious period on epidemics

NASA Astrophysics Data System (ADS)

Wilkinson, Robert R.; Sharkey, Kieran J.

2018-05-01

The duration of the infectious period is a crucial determinant of the ability of an infectious disease to spread. We consider an epidemic model that is network based and non-Markovian, containing classic Kermack-McKendrick, pairwise, message passing, and spatial models as special cases. For this model, we prove a monotonic relationship between the variability of the infectious period (with fixed mean) and the probability that the infection will reach any given subset of the population by any given time. For certain families of distributions, this result implies that epidemic severity is decreasing with respect to the variance of the infectious period. The striking importance of this relationship is demonstrated numerically. We then prove, with a fixed basic reproductive ratio (R0), a monotonic relationship between the variability of the posterior transmission probability (which is a function of the infectious period) and the probability that the infection will reach any given subset of the population by any given time. Thus again, even when R0 is fixed, variability of the infectious period tends to dampen the epidemic. Numerical results illustrate this but indicate the relationship is weaker. We then show how our results apply to message passing, pairwise, and Kermack-McKendrick epidemic models, even when they are not exactly consistent with the stochastic dynamics. For Poissonian contact processes, and arbitrarily distributed infectious periods, we demonstrate how systems of delay differential equations and ordinary differential equations can provide upper and lower bounds, respectively, for the probability that any given individual has been infected by any given time.

76 FR 5058 - Airports of Entry or Departure for Flights to and From Cuba

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-28

... [CBP Dec 11-05] RIN 1651-AA86 Airports of Entry or Departure for Flights to and From Cuba AGENCY: U.S... (DHS) regulations, direct flights between the United States and Cuba must arrive at or depart from one... Border Protection (CBP) to process authorized flights between the United States and Cuba. These...

An Application of Fuzzy Theory to Technical Competency Analysis for the Entry-Level Electronic Technician.

ERIC Educational Resources Information Center

Chang, Liang-Te; And Others

A study was conducted to develop the electronic technical competencies of duty and task analysis by using a revised DACUM (Developing a Curriculum) method, a questionnaire survey, and a fuzzy synthesis operation. The revised DACUM process relied on inviting electronics trade professionals to analyze electronic technology for entry-level…

15 CFR Appendix C to Part 30 - Summary of Exemptions and Exclusions From EEI Filing

Code of Federal Regulations, 2012 CFR

2012-01-01

... or transshipped and exported directly from the port of arrival never having made entry into the United States. If entry for consumption or warehousing in the United States is made, then an EEI is... foreign country. Goods that were imported under bond for processing and re-exportation are not covered by...

15 CFR Appendix C to Part 30 - Summary of Exemptions and Exclusions From EEI Filing

Code of Federal Regulations, 2011 CFR

2011-01-01

... or transshipped and exported directly from the port of arrival never having made entry into the United States. If entry for consumption or warehousing in the United States is made, then an EEI is... foreign country. Goods that were imported under bond for processing and re-exportation are not covered by...

Study of the Effectiveness of OCR for Decentralized Data Capture and Conversion. Final Report.

ERIC Educational Resources Information Center

Liston, David M.; And Others

The ERIC network conversion to an OCR (Optical Character Recognition) mode of data entry was studied to analyze the potential effectiveness of OCR data entry for future EPC/s (Editorial Processing Centers). Study results are also applicable to any other system involving decentralized bibliographic data capture and conversion functions. The report…

Effects of Froude number and geometry on water entry of a 2-D ellipse

NASA Astrophysics Data System (ADS)

Zhang, Xu; Liu, Pei-qing; Qu, Qiu-lin; Wang, Rui; Agarwal, Ramesh K.

2018-05-01

By using the finite volume method with volume of fluid model and global dynamic mesh technique, the effects of Froude number and geometry on the water entry process of a 2-D ellipse are investigated numerically. For the time history of the vertical force, the computational fluid dynamics (CFD) results match the experimental data much better than the classical potential-flow theories due to the consideration of the viscosity, turbulence, surface tension, gravity, and compressibility. The results show that the position of peak pressure on ellipse shifts from the spray root to the bottom of ellipse at a critical time. The critical time changes with the geometry and Froude number. By studying the vertical force, the ellipse water entry process can be divided into the initial and late stages based on the critical dimensionless time of about 0.1. The geometry of the ellipse plays a dominant role in the initial stage, while the Froude number is more important in the late stage of entry. The classical Wagner theory is extended to the ellipse water entry, and the predicted maximum value of vertical force coefficient in the initial stage is 4πa/b that matches the CFD results very well, where a and b are the horizontal axis and vertical axis of the ellipse parallel and perpendicular to the initial calm water surface, respectively.

The Biosurveillance Analytics Resource Directory (BARD): Facilitating the use of epidemiological models for infectious disease surveillance

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

Margevicius, Kristen J.; Generous, Nicholas; Abeyta, Esteban

Epidemiological modeling for infectious disease is important for disease management and its routine implementation needs to be facilitated through better description of models in an operational context. A standardized model characterization process that allows selection or making manual comparisons of available models and their results is currently lacking. A key need is a universal framework to facilitate model description and understanding of its features. Los Alamos National Laboratory (LANL) has developed a comprehensive framework that can be used to characterize an infectious disease model in an operational context. The framework was developed through a consensus among a panel of subjectmore » matter experts. In this paper, we describe the framework, its application to model characterization, and the development of the Biosurveillance Analytics Resource Directory (BARD; http://brd.bsvgateway.org/brd/), to facilitate the rapid selection of operational models for specific infectious/communicable diseases. We offer this framework and associated database to stakeholders of the infectious disease modeling field as a tool for standardizing model description and facilitating the use of epidemiological models.« less

[Emerging infectious diseases: complex, unpredictable processes].

PubMed

Guégan, Jean-François

2016-01-01

In the light of a double approach, at first empirical, later theoretical and comparative, illustrated by the example of the Buruli ulcer and its mycobacterial agent Mycobacterium ulcerans on which I focused my research activity these last ten years by studying determinants and factors of emerging infectious or parasitic diseases, the complexity of events explaining emerging diseases will be presented. The cascade of events occurring at various levels of spatiotemporal scales and organization of life, which lead to the numerous observed emergences, nowadays requires better taking into account the interactions between host(s), pathogen(s) and the environment by including the behavior of both individuals and the population. In numerous research studies on emerging infectious diseases, microbial hazard is described rather than infectious disease risk, the latter resulting from the confrontation between an association of threatening phenomena, or hazards, and a susceptible population. Beyond, the theme of emerging infectious diseases and its links with global environmental and societal changes leads to reconsider some well-established knowledge in infectiology and parasitology. © Société de Biologie, 2017.

The Biosurveillance Analytics Resource Directory (BARD): Facilitating the Use of Epidemiological Models for Infectious Disease Surveillance

PubMed Central

Margevicius, Kristen J; Generous, Nicholas; Abeyta, Esteban; Althouse, Ben; Burkom, Howard; Castro, Lauren; Daughton, Ashlynn; Del Valle, Sara Y.; Fairchild, Geoffrey; Hyman, James M.; Kiang, Richard; Morse, Andrew P.; Pancerella, Carmen M.; Pullum, Laura; Ramanathan, Arvind; Schlegelmilch, Jeffrey; Scott, Aaron; Taylor-McCabe, Kirsten J; Vespignani, Alessandro; Deshpande, Alina

2016-01-01

Epidemiological modeling for infectious disease is important for disease management and its routine implementation needs to be facilitated through better description of models in an operational context. A standardized model characterization process that allows selection or making manual comparisons of available models and their results is currently lacking. A key need is a universal framework to facilitate model description and understanding of its features. Los Alamos National Laboratory (LANL) has developed a comprehensive framework that can be used to characterize an infectious disease model in an operational context. The framework was developed through a consensus among a panel of subject matter experts. In this paper, we describe the framework, its application to model characterization, and the development of the Biosurveillance Analytics Resource Directory (BARD; http://brd.bsvgateway.org/brd/), to facilitate the rapid selection of operational models for specific infectious/communicable diseases. We offer this framework and associated database to stakeholders of the infectious disease modeling field as a tool for standardizing model description and facilitating the use of epidemiological models. PMID:26820405

The Biosurveillance Analytics Resource Directory (BARD): Facilitating the Use of Epidemiological Models for Infectious Disease Surveillance.

PubMed

Margevicius, Kristen J; Generous, Nicholas; Abeyta, Esteban; Althouse, Ben; Burkom, Howard; Castro, Lauren; Daughton, Ashlynn; Del Valle, Sara Y; Fairchild, Geoffrey; Hyman, James M; Kiang, Richard; Morse, Andrew P; Pancerella, Carmen M; Pullum, Laura; Ramanathan, Arvind; Schlegelmilch, Jeffrey; Scott, Aaron; Taylor-McCabe, Kirsten J; Vespignani, Alessandro; Deshpande, Alina

2016-01-01

Epidemiological modeling for infectious disease is important for disease management and its routine implementation needs to be facilitated through better description of models in an operational context. A standardized model characterization process that allows selection or making manual comparisons of available models and their results is currently lacking. A key need is a universal framework to facilitate model description and understanding of its features. Los Alamos National Laboratory (LANL) has developed a comprehensive framework that can be used to characterize an infectious disease model in an operational context. The framework was developed through a consensus among a panel of subject matter experts. In this paper, we describe the framework, its application to model characterization, and the development of the Biosurveillance Analytics Resource Directory (BARD; http://brd.bsvgateway.org/brd/), to facilitate the rapid selection of operational models for specific infectious/communicable diseases. We offer this framework and associated database to stakeholders of the infectious disease modeling field as a tool for standardizing model description and facilitating the use of epidemiological models.

The Biosurveillance Analytics Resource Directory (BARD): Facilitating the use of epidemiological models for infectious disease surveillance

DOE PAGES

Margevicius, Kristen J.; Generous, Nicholas; Abeyta, Esteban; ...

2016-01-28

Epidemiological modeling for infectious disease is important for disease management and its routine implementation needs to be facilitated through better description of models in an operational context. A standardized model characterization process that allows selection or making manual comparisons of available models and their results is currently lacking. A key need is a universal framework to facilitate model description and understanding of its features. Los Alamos National Laboratory (LANL) has developed a comprehensive framework that can be used to characterize an infectious disease model in an operational context. The framework was developed through a consensus among a panel of subjectmore » matter experts. In this paper, we describe the framework, its application to model characterization, and the development of the Biosurveillance Analytics Resource Directory (BARD; http://brd.bsvgateway.org/brd/), to facilitate the rapid selection of operational models for specific infectious/communicable diseases. We offer this framework and associated database to stakeholders of the infectious disease modeling field as a tool for standardizing model description and facilitating the use of epidemiological models.« less

The climate change-infectious disease nexus: is it time for climate change syndemics?

PubMed

Heffernan, Claire

2013-12-01

Conceptualizing climate as a distinct variable limits our understanding of the synergies and interactions between climate change and the range of abiotic and biotic factors, which influence animal health. Frameworks such as eco-epidemiology and the epi-systems approach, while more holistic, view climate and climate change as one of many discreet drivers of disease. Here, I argue for a new paradigmatic framework: climate-change syndemics. Climate-change syndemics begins from the assumption that climate change is one of many potential influences on infectious disease processes, but crucially is unlikely to act independently or in isolation; and as such, it is the inter-relationship between factors that take primacy in explorations of infectious disease and climate change. Equally importantly, as climate change will impact a wide range of diseases, the frame of analysis is at the collective rather than individual level (for both human and animal infectious disease) across populations.

Chemotherapy Order Entry by a Clinical Support Pharmacy Technician in an Outpatient Medical Day Unit

PubMed Central

Neville, Heather; Broadfield, Larry; Harding, Claudia; Heukshorst, Shelley; Sweetapple, Jennifer; Rolle, Megan

2016-01-01

Background: Pharmacy technicians are expanding their scope of practice, often in partnership with pharmacists. In oncology, such a shift in responsibilities may lead to workflow efficiencies, but may also cause concerns about patient risk and medication errors. Objectives: The primary objective was to compare the time spent on order entry and order-entry checking before and after training of a clinical support pharmacy technician (CSPT) to perform chemotherapy order entry. The secondary objectives were to document workflow interruptions and to assess medication errors. Methods: This before-and-after observational study investigated chemotherapy order entry for ambulatory oncology patients. Order entry was performed by pharmacists before the process change (phase 1) and by 1 CSPT after the change (phase 2); order-entry checking was performed by a pharmacist during both phases. The tasks were timed by an independent observer using a personal digital assistant. A convenience sample of 125 orders was targeted for each phase. Data were exported to Microsoft Excel software, and timing differences for each task were tested with an unpaired t test. Results: Totals of 143 and 128 individual orders were timed for order entry during phase 1 (pharmacist) and phase 2 (CSPT), respectively. The mean total time to perform order entry was greater during phase 1 (1:37 min versus 1:20 min; p = 0.044). Totals of 144 and 122 individual orders were timed for order-entry checking (by a pharmacist) in phases 1 and 2, respectively, and there was no difference in mean total time for order-entry checking (1:21 min versus 1:20 min; p = 0.69). There were 33 interruptions not related to order entry (totalling 39:38 min) during phase 1 and 25 interruptions (totalling 30:08 min) during phase 2. Three errors were observed during order entry in phase 1 and one error during order-entry checking in phase 2; the errors were rated as having no effect on patient care. Conclusions: Chemotherapy order entry by a trained CSPT appeared to be just as safe and efficient as order entry by a pharmacist. Changes in pharmacy technicians’ scope of practice could increase the amount of time available for pharmacists to provide direct patient care in the oncology setting. PMID:27402999

Chemotherapy Order Entry by a Clinical Support Pharmacy Technician in an Outpatient Medical Day Unit.

PubMed

Neville, Heather; Broadfield, Larry; Harding, Claudia; Heukshorst, Shelley; Sweetapple, Jennifer; Rolle, Megan

2016-01-01

Pharmacy technicians are expanding their scope of practice, often in partnership with pharmacists. In oncology, such a shift in responsibilities may lead to workflow efficiencies, but may also cause concerns about patient risk and medication errors. The primary objective was to compare the time spent on order entry and order-entry checking before and after training of a clinical support pharmacy technician (CSPT) to perform chemotherapy order entry. The secondary objectives were to document workflow interruptions and to assess medication errors. This before-and-after observational study investigated chemotherapy order entry for ambulatory oncology patients. Order entry was performed by pharmacists before the process change (phase 1) and by 1 CSPT after the change (phase 2); order-entry checking was performed by a pharmacist during both phases. The tasks were timed by an independent observer using a personal digital assistant. A convenience sample of 125 orders was targeted for each phase. Data were exported to Microsoft Excel software, and timing differences for each task were tested with an unpaired t test. Totals of 143 and 128 individual orders were timed for order entry during phase 1 (pharmacist) and phase 2 (CSPT), respectively. The mean total time to perform order entry was greater during phase 1 (1:37 min versus 1:20 min; p = 0.044). Totals of 144 and 122 individual orders were timed for order-entry checking (by a pharmacist) in phases 1 and 2, respectively, and there was no difference in mean total time for order-entry checking (1:21 min versus 1:20 min; p = 0.69). There were 33 interruptions not related to order entry (totalling 39:38 min) during phase 1 and 25 interruptions (totalling 30:08 min) during phase 2. Three errors were observed during order entry in phase 1 and one error during order-entry checking in phase 2; the errors were rated as having no effect on patient care. Chemotherapy order entry by a trained CSPT appeared to be just as safe and efficient as order entry by a pharmacist. Changes in pharmacy technicians' scope of practice could increase the amount of time available for pharmacists to provide direct patient care in the oncology setting.

Parallel pulse processing and data acquisition for high speed, low error flow cytometry

DOEpatents

van den Engh, Gerrit J.; Stokdijk, Willem

1992-01-01

A digitally synchronized parallel pulse processing and data acquisition system for a flow cytometer has multiple parallel input channels with independent pulse digitization and FIFO storage buffer. A trigger circuit controls the pulse digitization on all channels. After an event has been stored in each FIFO, a bus controller moves the oldest entry from each FIFO buffer onto a common data bus. The trigger circuit generates an ID number for each FIFO entry, which is checked by an error detection circuit. The system has high speed and low error rate.

Structural and Functional Studies on the Marburg Virus GP2 Fusion Loop.

PubMed

Liu, Nina; Tao, Yisong; Brenowitz, Michael D; Girvin, Mark E; Lai, Jonathan R

2015-10-01

Marburg virus (MARV) and the ebolaviruses belong to the family Filoviridae (the members of which are filoviruses) that cause severe hemorrhagic fever. Infection requires fusion of the host and viral membranes, a process that occurs in the host cell endosomal compartment and is facilitated by the envelope glycoprotein fusion subunit, GP2. The N-terminal fusion loop (FL) of GP2 is a hydrophobic disulfide-bonded loop that is postulated to insert and disrupt the host endosomal membrane during fusion. Here, we describe the first structural and functional studies of a protein corresponding to the MARV GP2 FL. We found that this protein undergoes a pH-dependent conformational change, as monitored by circular dichroism and nuclear magnetic resonance. Furthermore, we report that, under low pH conditions, the MARV GP2 FL can induce content leakage from liposomes. The general aspects of this pH-dependent structure and lipid-perturbing behavior are consistent with previous reports on Ebola virus GP2 FL. However, nuclear magnetic resonance studies in lipid bicelles and mutational analysis indicate differences in structure exist between MARV and Ebola virus GP2 FL. These results provide new insight into the mechanism of MARV GP2-mediated cell entry. © The Author 2015. 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.

Validation of daily increments and a marine-entry check in the otoliths of sockeye salmon Oncorhynchus nerka post-smolts.

PubMed

Freshwater, C; Trudel, M; Beacham, T D; Neville, C-E; Tucker, S; Juanes, F

2015-07-01

Juvenile sockeye salmon Oncorhynchus nerka that were reared and smolted in laboratory conditions were found to produce otolith daily increments, as well as a consistently visible marine-entry check formed during their transition to salt water. Field-collected O. nerka post-smolts of an equivalent age also displayed visible checks; however, microchemistry estimates of marine-entry date using Sr:Ca ratios differed from visual estimates by c. 9 days suggesting that microstructural and microchemical processes occur on different time scales. © 2015 The Fisheries Society of the British Isles.

Space Shuttle third flight /STS-3/ entry RCS analysis. [Reaction Control System

NASA Technical Reports Server (NTRS)

Scallion, W. I.; Compton, H. R.; Suit, W. T.; Powell, R. W.; Blackstock, T. A.; Bates, B. L.

1983-01-01

Flight data obtained from three Space Transportation System orbiter entries (STS-1, 2, and 3) are processed and analyzed to determine the roll interactions caused by the firing of the entry reaction control system (RCS). Comparisons between the flight-derived parameters and the predicted derivatives without interaction effects are made. The flight-derived RCS Plume flow-field interaction effects are independently deduced by direct integration of the incremental changes in the wing upper surface pressures induced by RCS side thruster firings. The separately obtained interaction effects are compared to the predicted values and the differences are discussed.

Viral entry mechanisms: the increasing diversity of paramyxovirus entry

PubMed Central

Smith, Everett Clinton; Popa, Andreea; Chang, Andres; Masante, Cyril; Dutch, Rebecca Ellis

2009-01-01

The paramyxovirus family contains established human pathogens such as measles virus and human respiratory syncytial virus, and emerging pathogens including the Hendra and Nipah viruses and the recently identified human metapneumovirus. Two major envelope glycoproteins, the attachment protein and the fusion protein, promote the processes of viral attachment and virus-cell membrane fusion required for entry. While common mechanisms of fusion protein proteolytic activation and the mechanism of membrane fusion promotion have been shown in recent years, considerable diversity exists in the family related to receptor binding and the potential mechanisms of fusion triggering. PMID:19878307

Changes, disruption and innovation: An investigation of the introduction of new health information technology in a microbiology laboratory.

PubMed

Toouli, George; Georgiou, Andrew; Westbrook, Johanna

2012-01-01

It is expected that health information technology (HIT) will deliver a safer, more efficient and effective health care system. The aim of this study was to undertake a qualitative and video-ethnographic examination of the impact of information technologies on work processes in the reception area of a Microbiology Department, to ascertain what changed, how it changed and the impact of the change. The setting for this study was the microbiology laboratory of a large tertiary hospital in Sydney. The study consisted of qualitative (interview and focus group) data and observation sessions for the period August 2005 to October 2006 along with video footage shot in three sessions covering the original system and the two stages of the Cerner implementation. Data analysis was assisted by NVivo software and process maps were produced from the video footage. There were two laboratory information systems observed in the video footage with computerized provider order entry introduced four months later. Process maps highlighted the large number of pre data entry steps with the original system whilst the newer system incorporated many of these steps in to the data entry stage. However, any time saved with the new system was offset by the requirement to complete some data entry of patient information not previously required. Other changes noted included the change of responsibilities for the reception staff and the physical changes required to accommodate the increased activity around the data entry area. Implementing a new HIT is always an exciting time for any environment but ensuring that the implementation goes smoothly and with minimal trouble requires the administrator and their team to plan well in advance for staff training, physical layout and possible staff resource reallocation.

Preparing South Carolina Emergency Departments for Mass Casualties with an Emphasis on the Planning Process

DTIC Science & Technology

2013-03-01

population for patients with symptoms of acute infectious disease, especially smallpox, anthrax, plague, tularemia , and influenza 19 • 50 cases...disease, especially smallpox, anthrax, plague, tularemia , and influenza • 50 cases per million population for patients with symptoms of acute...an additional 1,548–2064 patients with symptoms of acute infectious disease, especially smallpox, anthrax, plague, tularemia , and influenza to be

Dysfunction of bovine endogenous retrovirus K2 envelope glycoprotein is related to unsuccessful intracellular trafficking.

PubMed

Nakaya, Yuki; Miyazawa, Takayuki

2014-06-01

Endogenous retroviruses (ERVs) are the remnants of retroviral infection of ancestral germ cells. Mutations introduced into ERVs halt the production of infectious agents, but their effects on the function of retroviral proteins are not fully understood. Retroviral envelope glycoproteins (Envs) are utilized in membrane fusion during viral entry, and we recently identified intact coding sequences for bovine endogenous retrovirus K1 (BERV-K1) and BERV-K2 Envs. Amino acid sequences of BERV-K1 Env (also called Fematrin-1) and BERV-K2 Env are similar, and both viruses are classified in the genus Betaretrovirus. While Fematrin-1 plays an important role in cell-to-cell fusion in bovine placenta, the BERV-K2 envelope gene is marginally expressed in vivo, and its recombinant Env protein is defective in membrane fusion due to inefficient cleavage of surface (SU) and transmembrane subunits. Here, we conducted chimeric analyses of Fematrin-1 and BERV-K2 Envs and revealed that defective maturation of BERV-K2 Env contributed to failed intracellular trafficking. Fluorescence microscopy and flow cytometric analysis suggested that in contrast to Fematrin-1 Env, BERV-K2 Env could not be transported from the endoplasmic reticulum to the trans-Golgi network, where cellular proteases required for processing retroviral Envs are localized. We also identified that one of the responsive regions of this phenomenon resided within a 65-amino-acid region of BERV-K2 SU. This is the first report to identify that retroviral Env SU is involved in the regulation of intracellular trafficking, and it may help to elucidate the maturation process of Fematrin-1 and other related Envs. Retroviruses utilize envelope glycoproteins (Envs) to enter host target cells. Mature retroviral Env is a heterodimer, which consists of surface (SU) and transmembrane (TM) subunits that are generated by the cleavage of an Env precursor protein in the trans-Golgi network. SU and TM mediate the recognition of the entry receptor and virus-host membrane fusion, respectively. However, unexplained issues remain for the maturation process of retroviral Env. We previously reported that bovine endogenous retrovirus K2 (BERV-K2) Env lost fusogenicity due to a defect in the cleavage of SU and TM. In this study, we identified that mutations residing in BERV-K2 SU disturbed intracellular trafficking of BERV-K2 Env and resulted its inefficient cleavage. Because SU is not known to play an important role in this process, our study may provide novel insights into the maturation mechanism of retroviral Envs. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Inhibitors of the entry of HIV into host cells.

PubMed

Meanwell, Nicholas A; Kadow, John F

2003-07-01

The development of mechanistic insight into the process by which HIV enters host cells has revealed a panoply of targets that offer considerable potential as sites for pharmacological intervention. The gp120/gp41 protein complex, expressed on the virion surface, mediates HIV entry by a process initiated by the engagement of the host cell receptor CD4. Subtle conformational changes triggered by this interaction expose elements of gp120 to the seven-transmembrane, G protein-coupled chemokine receptors CCR5 or CXCR4 expressed on host cells, a contact that relieves constraints imposed on gp41 by gp120. This leads to a major conformational rearrangement of gp41, which results in the insertion of the fusion peptide into the host cell membrane and the assembly of the amino terminus heptad repeat into a trimeric form that is subsequently recognized by the carboxy terminal heptad repeat. The latter process leads to juxtaposition of the viral and host cell membranes, a prelude to fusion. The most prominent strategies and targets that are actively being exploited as drug discovery opportunities are inhibition of the attachment of HIV to host cells, blockade of chemokine receptors and interference with the function of gp41. Inhibitors of each of these steps in the HIV entry process with potential clinical relevance are reviewed in the context of their status in the drug development process. The most significant entity to emerge from this area of research to date is enfuvirtide, a 36-amino acid derivative that interferes with the function of gp41. Enfuvirtide is the first HIV entry inhibitor to be granted a license for marketing (it was approved in the US and Europe in March 2003), and its introduction portends the beginning of what promises to be an exciting new era of HIV therapy.

Mars Entry Atmospheric Data System Modelling and Algorithm Development

NASA Technical Reports Server (NTRS)

Karlgaard, Christopher D.; Beck, Roger E.; OKeefe, Stephen A.; Siemers, Paul; White, Brady; Engelund, Walter C.; Munk, Michelle M.

2009-01-01

The Mars Entry Atmospheric Data System (MEADS) is being developed as part of the Mars Science Laboratory (MSL), Entry, Descent, and Landing Instrumentation (MEDLI) project. The MEADS project involves installing an array of seven pressure transducers linked to ports on the MSL forebody to record the surface pressure distribution during atmospheric entry. These measured surface pressures are used to generate estimates of atmospheric quantities based on modeled surface pressure distributions. In particular, the quantities to be estimated from the MEADS pressure measurements include the total pressure, dynamic pressure, Mach number, angle of attack, and angle of sideslip. Secondary objectives are to estimate atmospheric winds by coupling the pressure measurements with the on-board Inertial Measurement Unit (IMU) data. This paper provides details of the algorithm development, MEADS system performance based on calibration, and uncertainty analysis for the aerodynamic and atmospheric quantities of interest. The work presented here is part of the MEDLI performance pre-flight validation and will culminate with processing flight data after Mars entry in 2012.

The use of a personal digital assistant for wireless entry of data into a database via the Internet.

PubMed

Fowler, D L; Hogle, N J; Martini, F; Roh, M S

2002-01-01

Researchers typically record data on a worksheet and at some later time enter it into the database. Wireless data entry and retrieval using a personal digital assistant (PDA) at the site of patient contact can simplify this process and improve efficiency. A surgeon and a nurse coordinator provided the content for the database. The computer programmer created the database, placed the pages of the database on the PDA screen, and researched and installed security measures. Designing the database took 6 months. Meeting Health Insurance Portability and Accountability Act of 1996 (HIPAA) requirements for patient confidentiality, satisfying institutional Information Services requirements, and ensuring connectivity required an additional 8 months before the functional system was complete. It is now possible to achieve wireless entry and retrieval of data using a PDA. Potential advantages include collection and entry of data at the same time, easy entry of data from multiple sites, and retrieval of data at the patient's bedside.

Fused silica reflecting heat shields for outer planet entry probes

NASA Technical Reports Server (NTRS)

Congdon, W. M.; Peterson, D. L.

1975-01-01

The development of slip-cast fused silica is discussed as a heat shield designed to meet the needs of outer-planet entry probes. The distinguishing feature of silica is its ability to reflect the radiation imposed by planetary-entry environments. This reflectivity is particularly sensitive to degradation by the presence of trace amounts of contaminants introduced by the starting materials or by processing. The microstructure of a silica configuration also significantly influences the reflectivity and other thermomechanical properties. The processing techniques attendant on controlling microstructure while maintaining purity are discussed. The selection of a starting material of essential purity precludes the use of purified natural quartz and requires the use of synthetic fused silica. The silica is characterized in a limited combined heating test environment. The surface mass loss is controlled by liquid runoff from a relatively low-temperature melt layer; the reflectance is basically maintained and the material achieves a surprisingly high heat of ablation.

Paramyxovirus Glycoproteins and the Membrane Fusion Process.

PubMed

Aguilar, Hector C; Henderson, Bryce A; Zamora, J Lizbeth; Johnston, Gunner P

2016-09-01

The family Paramyxoviridae includes many viruses that significantly affect human and animal health. An essential step in the paramyxovirus life cycle is viral entry into host cells, mediated by virus-cell membrane fusion. Upon viral entry, infection results in expression of the paramyxoviral glycoproteins on the infected cell surface. This can lead to cell-cell fusion (syncytia formation), often linked to pathogenesis. Thus membrane fusion is essential for both viral entry and cell-cell fusion and an attractive target for therapeutic development. While there are important differences between viral-cell and cell-cell membrane fusion, many aspects are conserved. The paramyxoviruses generally utilize two envelope glycoproteins to orchestrate membrane fusion. Here, we discuss the roles of these glycoproteins in distinct steps of the membrane fusion process. These findings can offer insights into evolutionary relationships among Paramyxoviridae genera and offer future targets for prophylactic and therapeutic development.

Paramyxovirus Glycoproteins and the Membrane Fusion Process

PubMed Central

Aguilar, Hector C.; Henderson, Bryce A.; Zamora, J. Lizbeth; Johnston, Gunner P.

2016-01-01

The family Paramyxoviridae includes many viruses that significantly affect human and animal health. An essential step in the paramyxovirus life cycle is viral entry into host cells, mediated by virus-cell membrane fusion. Upon viral entry, infection results in expression of the paramyxoviral glycoproteins on the infected cell surface. This can lead to cell-cell fusion (syncytia formation), often linked to pathogenesis. Thus membrane fusion is essential for both viral entry and cell-cell fusion and an attractive target for therapeutic development. While there are important differences between viral-cell and cell-cell membrane fusion, many aspects are conserved. The paramyxoviruses generally utilize two envelope glycoproteins to orchestrate membrane fusion. Here, we discuss the roles of these glycoproteins in distinct steps of the membrane fusion process. These findings can offer insights into evolutionary relationships among Paramyxoviridae genera and offer future targets for prophylactic and therapeutic development. PMID:28138419

ALCHEMIST (Anesthesia Log, Charge Entry, Medical Information, and Statistics)

PubMed Central

Covey, M. Carl

1979-01-01

This paper presents an automated system for the handling of charges and information processing within the Anesthesiology department of the University of Arkansas for the Medical Sciences (UAMS). The purpose of the system is to take the place of cumbersome, manual billing procedures and in the process of automated charge generation, to compile a data base of patient data for later use. ALCHEMIST has demonstrated its value by increasing both the speed and the accuracy of generation of patient charges as well as facilitating the compilation of valuable, informative reports containing statistical summaries of all aspects of the UAMS operating wing case load. ALCHEMIST allows for the entry of fifty different sets of information (multiple items in some sets) for a total of 107 separate data elements from the original anesthetic record. All this data is entered as part of the charge entry procedure.

Structural Genomics and Drug Discovery for Infectious Diseases

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

Anderson, W.F.

The application of structural genomics methods and approaches to proteins from organisms causing infectious diseases is making available the three dimensional structures of many proteins that are potential drug targets and laying the groundwork for structure aided drug discovery efforts. There are a number of structural genomics projects with a focus on pathogens that have been initiated worldwide. The Center for Structural Genomics of Infectious Diseases (CSGID) was recently established to apply state-of-the-art high throughput structural biology technologies to the characterization of proteins from the National Institute for Allergy and Infectious Diseases (NIAID) category A-C pathogens and organisms causing emerging,more » or re-emerging infectious diseases. The target selection process emphasizes potential biomedical benefits. Selected proteins include known drug targets and their homologs, essential enzymes, virulence factors and vaccine candidates. The Center also provides a structure determination service for the infectious disease scientific community. The ultimate goal is to generate a library of structures that are available to the scientific community and can serve as a starting point for further research and structure aided drug discovery for infectious diseases. To achieve this goal, the CSGID will determine protein crystal structures of 400 proteins and protein-ligand complexes using proven, rapid, highly integrated, and cost-effective methods for such determination, primarily by X-ray crystallography. High throughput crystallographic structure determination is greatly aided by frequent, convenient access to high-performance beamlines at third-generation synchrotron X-ray sources.« less

Visible-light-responsive ZnCuO nanoparticles: benign photodynamic killers of infectious protozoans

PubMed Central

Nadhman, Akhtar; Nazir, Samina; Khan, Malik Ihsanullah; Ayub, Attiya; Muhammad, Bakhtiar; Khan, Momin; Shams, Dilawar Farhan; Yasinzai, Masoom

2015-01-01

Human beings suffer from several infectious agents such as viruses, bacteria, and protozoans. Recently, there has been a great interest in developing biocompatible nanostructures to deal with infectious agents. This study investigated benign ZnCuO nanostructures that were visible-light-responsive due to the resident copper in the lattice. The nanostructures were synthesized through a size-controlled hot-injection process, which was adaptable to the surface ligation processes. The nanostructures were then characterized through transmission electron microscopy, X-ray diffraction, diffused reflectance spectroscopy, Rutherford backscattering, and photoluminescence analysis to measure crystallite nature, size, luminescence, composition, and band-gap analyses. Antiprotozoal efficiency of the current nanoparticles revealed the photodynamic killing of Leishmania protozoan, thus acting as efficient metal-based photosensitizers. The crystalline nanoparticles showed good biocompatibility when tested for macrophage toxicity and in hemolysis assays. The study opens a wide avenue for using toxic material in resident nontoxic forms as an effective antiprotozoal treatment. PMID:26604755

Validation of Autoclave Protocols for Successful Decontamination of Category A Medical Waste Generated from Care of Patients with Serious Communicable Diseases

PubMed Central

Reimers, Mallory; Ernst, Neysa; Bova, Gregory; Nowakowski, Elaine; Bukowski, James; Ellis, Brandon C.; Smith, Chris; Sauer, Lauren; Dionne, Kim; Carroll, Karen C.; Maragakis, Lisa L.; Parrish, Nicole M.

2016-01-01

ABSTRACT In response to the Ebola outbreak in 2014, many hospitals designated specific areas to care for patients with Ebola and other highly infectious diseases. The safe handling of category A infectious substances is a unique challenge in this environment. One solution is on-site waste treatment with a steam sterilizer or autoclave. The Johns Hopkins Hospital (JHH) installed two pass-through autoclaves in its biocontainment unit (BCU). The JHH BCU and The Johns Hopkins biosafety level 3 (BSL-3) clinical microbiology laboratory designed and validated waste-handling protocols with simulated patient trash to ensure adequate sterilization. The results of the validation process revealed that autoclave factory default settings are potentially ineffective for certain types of medical waste and highlighted the critical role of waste packaging in successful sterilization. The lessons learned from the JHH validation process can inform the design of waste management protocols to ensure effective treatment of highly infectious medical waste. PMID:27927920

Some considerations concerning the challenge of incorporating social variables into epidemiological models of infectious disease transmission.

PubMed

Barnett, Tony; Fournié, Guillaume; Gupta, Sunetra; Seeley, Janet

2015-01-01

Incorporation of 'social' variables into epidemiological models remains a challenge. Too much detail and models cease to be useful; too little and the very notion of infection - a highly social process in human populations - may be considered with little reference to the social. The French sociologist Émile Durkheim proposed that the scientific study of society required identification and study of 'social currents'. Such 'currents' are what we might today describe as 'emergent properties', specifiable variables appertaining to individuals and groups, which represent the perspectives of social actors as they experience the environment in which they live their lives. Here we review the ways in which one particular emergent property, hope, relevant to a range of epidemiological situations, might be used in epidemiological modelling of infectious diseases in human populations. We also indicate how such an approach might be extended to include a range of other potential emergent properties to represent complex social and economic processes bearing on infectious disease transmission.

Validation of Autoclave Protocols for Successful Decontamination of Category A Medical Waste Generated from Care of Patients with Serious Communicable Diseases.

PubMed

Garibaldi, Brian T; Reimers, Mallory; Ernst, Neysa; Bova, Gregory; Nowakowski, Elaine; Bukowski, James; Ellis, Brandon C; Smith, Chris; Sauer, Lauren; Dionne, Kim; Carroll, Karen C; Maragakis, Lisa L; Parrish, Nicole M

2017-02-01

In response to the Ebola outbreak in 2014, many hospitals designated specific areas to care for patients with Ebola and other highly infectious diseases. The safe handling of category A infectious substances is a unique challenge in this environment. One solution is on-site waste treatment with a steam sterilizer or autoclave. The Johns Hopkins Hospital (JHH) installed two pass-through autoclaves in its biocontainment unit (BCU). The JHH BCU and The Johns Hopkins biosafety level 3 (BSL-3) clinical microbiology laboratory designed and validated waste-handling protocols with simulated patient trash to ensure adequate sterilization. The results of the validation process revealed that autoclave factory default settings are potentially ineffective for certain types of medical waste and highlighted the critical role of waste packaging in successful sterilization. The lessons learned from the JHH validation process can inform the design of waste management protocols to ensure effective treatment of highly infectious medical waste. Copyright © 2017 American Society for Microbiology.

Handheld vs. laptop computers for electronic data collection in clinical research: a crossover randomized trial.

PubMed

Haller, Guy; Haller, Dagmar M; Courvoisier, Delphine S; Lovis, Christian

2009-01-01

To compare users' speed, number of entry errors and satisfaction in using two current devices for electronic data collection in clinical research: handheld and laptop computers. The authors performed a randomized cross-over trial using 160 different paper-based questionnaires and representing altogether 45,440 variables. Four data coders were instructed to record, according to a random predefined and equally balanced sequence, the content of these questionnaires either on a laptop or on a handheld computer. Instructions on the kind of device to be used were provided to data-coders in individual sealed and opaque envelopes. Study conditions were controlled and the data entry process performed in a quiet environment. The authors compared the duration of the data recording process, the number of errors and users' satisfaction with the two devices. The authors divided errors into two separate categories, typing and missing data errors. The original paper-based questionnaire was used as a gold-standard. The overall duration of the recording process was significantly reduced (2.0 versus 3.3 min) when data were recorded on the laptop computer (p < 0.001). Data accuracy also improved. There were 5.8 typing errors per 1,000 entries with the laptop compared to 8.4 per 1,000 with the handheld computer (p < 0.001). The difference was even more important for missing data which decreased from 22.8 to 2.9 per 1,000 entries when a laptop was used (p < 0.001). Users found the laptop easier, faster and more satisfying to use than the handheld computer. Despite the increasing use of handheld computers for electronic data collection in clinical research, these devices should be used with caution. They double the duration of the data entry process and significantly increase the risk of typing errors and missing data. This may become a particularly crucial issue in studies where these devices are provided to patients or healthcare workers, unfamiliar with computer technologies, for self-reporting or research data collection processes.

Handheld vs. Laptop Computers for Electronic Data Collection in Clinical Research: A Crossover Randomized Trial

PubMed Central

Haller, Guy; Haller, Dagmar M.; Courvoisier, Delphine S.; Lovis, Christian

2009-01-01

Objective To compare users' speed, number of entry errors and satisfaction in using two current devices for electronic data collection in clinical research: handheld and laptop computers. Design The authors performed a randomized cross-over trial using 160 different paper-based questionnaires and representing altogether 45,440 variables. Four data coders were instructed to record, according to a random predefined and equally balanced sequence, the content of these questionnaires either on a laptop or on a handheld computer. Instructions on the kind of device to be used were provided to data-coders in individual sealed and opaque envelopes. Study conditions were controlled and the data entry process performed in a quiet environment. Measurements The authors compared the duration of the data recording process, the number of errors and users' satisfaction with the two devices. The authors divided errors into two separate categories, typing and missing data errors. The original paper-based questionnaire was used as a gold-standard. Results The overall duration of the recording process was significantly reduced (2.0 versus 3.3 min) when data were recorded on the laptop computer (p < 0.001). Data accuracy also improved. There were 5.8 typing errors per 1,000 entries with the laptop compared to 8.4 per 1,000 with the handheld computer (p < 0.001). The difference was even more important for missing data which decreased from 22.8 to 2.9 per 1,000 entries when a laptop was used (p < 0.001). Users found the laptop easier, faster and more satisfying to use than the handheld computer. Conclusions Despite the increasing use of handheld computers for electronic data collection in clinical research, these devices should be used with caution. They double the duration of the data entry process and significantly increase the risk of typing errors and missing data. This may become a particularly crucial issue in studies where these devices are provided to patients or healthcare workers, unfamiliar with Computer Technologies, for self-reporting or research data collection processes. PMID:19567799

The double burden of disease among mining workers in Papua, Indonesia: at the crossroads between Old and New health paradigms.

PubMed

Rodriguez-Fernandez, Rodrigo; Ng, Nawi; Susilo, Dwidjo; Prawira, John; Bangs, Michael J; Amiya, Rachel M

2016-09-08

As the global shift toward non-communicable diseases overlaps with the unfinished agenda of confronting infectious diseases in low- and middle-income countries, epidemiological links across both burdens must be recognized. This study examined the non-communicable disease-infectious disease overlap in the specific comorbidity rates for key diseases in an occupational cohort in Papua, Indonesia. Diagnosed cases of ischaemic heart disease, stroke, hypertension, diabetes (types 1 and 2), chronic obstructive pulmonary disease, asthma, cancer, HIV and AIDS, tuberculosis, and malaria were extracted from 22,550 patient records (21,513 men, 1037 women) stored in identical electronic health information systems from two clinic sites in Papua, Indonesia. Data were collected as International Classification of Diseases, 10th Revision, entries from records spanning January-December 2013. A novel application of Circos software was used to visualize the interconnectedness between the disease burdens as overlapping prevalence estimates representing comorbidities. Overall, NCDs represented 38 % of all disease cases, primarily in the form of type 2 diabetes (n = 1440) and hypertension (n = 1398). Malaria cases represented the largest single portion of the disease burden with 5310 recorded cases, followed by type 2 diabetes with 1400 cases. Tuberculosis occurred most frequently alongside malaria (29 %), followed by chronic obstructive pulmonary disease (19 %), asthma (17 %), and stroke (12 %). Hypertension-tuberculosis (4 %), tuberculosis-cancer (4 %), and asthma-tuberculosis (2 %) comorbidities were also observed. The high prevalence of multimorbidity, preponderance of non-communicable diseases, and extensive interweaving of non-communicable and infectious disease comorbidities highlighted in this cohort of mining workers in Papua, Indonesia reflect the markedly double disease burden increasingly plaguing Indonesia and other similar low- and middle-income countries - a challenge with which their over-stretched, under-resourced health systems are ill-equipped to cope. Integrated, person-centered treatment and control strategies rooted in the primary healthcare sector will be critical to reverse this trend.

Apolipoprotein B100 is required for hepatitis C infectivity and Mipomersen inhibits hepatitis C

PubMed Central

Schaefer, Esperance A K; Meixiong, James; Mark, Christina; Deik, Amy; Motola, Daniel L; Fusco, Dahlene; Yang, Andrew; Brisac, Cynthia; Salloum, Shadi; Lin, Wenyu; Clish, Clary B; Peng, Lee F; Chung, Raymond T

2016-01-01

AIM To characterize the role of apolipoprotein B100 (apoB100) in hepatitis C viral (HCV) infection. METHODS In this study, we utilize a gene editing tool, transcription activator-like effector nucleases (TALENs), to generate human hepatoma cells with a stable genetic deletion of APOB to assess of apoB in HCV. Using infectious cell culture-competent HCV, viral pseudoparticles, replicon models, and lipidomic analysis we determined the contribution of apoB to each step of the viral lifecycle. We further studied the effect of mipomersen, an FDA-approved antisense inhibitor of apoB100, on HCV using in vitro cell-culture competent HCV and determined its impact on viral infectivity with the TCID50 method. RESULTS We found that apoB100 is indispensable for HCV infection. Using the JFH-1 fully infectious cell-culture competent virus in Huh 7 hepatoma cells with TALEN-mediated gene deletion of apoB (APOB KO), we found a significant reduction in HCV RNA and protein levels following infection. Pseudoparticle and replicon models demonstrated that apoB did not play a role in HCV entry or replication. However, the virus produced by APOB KO cells had significantly diminished infectivity as measured by the TCID-50 method compared to wild-type virus. Lipidomic analysis demonstrated that these virions have a fundamentally altered lipidome, with complete depletion of cholesterol esters. We further demonstrate that inhibition of apoB using mipomersen, an FDA-approved anti-sense oligonucleotide, results in a potent anti-HCV effect and significantly reduces the infectivity of the virus. CONCLUSION ApoB is required for the generation of fully infectious HCV virions, and inhibition of apoB with mipomersen blocks HCV. Targeting lipid metabolic pathways to impair viral infectivity represents a novel host targeted strategy to inhibit HCV. PMID:28018102

STD 105: Process Groups as an Instructional Medium for Re-entry Women at Paul D. Camp Community College.

ERIC Educational Resources Information Center

Creamer, Elizabeth; Duggin, Molly; Kidd, Ronald

1999-01-01

An effective team-based, group-oriented personal development from a woman's perspective course explores the effects of several issues on the re-entry woman: the role that society and culture play in influencing women's vocational choices; women's roles; the economic necessity of work; stress; and relationships. A team-based approach provides a…

Development of a Screening Methodology for Entry into Medical Technical Training Courses. Final Report for Period October 1975-April 1977.

ERIC Educational Resources Information Center

Leisey, Sandra A.; Guinn, Nancy

At the request of the Air Force School of Aviation Medicine, a project was initiated to evaluate the current screening process used for entry into three medical technical training courses: Aeromedical Specialist, Environmental Health Specialist, and Physiological Training Specialist. A sample of 1,003 students were administered the General…

Survey of New Jersey Public School Districts Using Computers and Data Entry Equipment.

ERIC Educational Resources Information Center

Gaydos, Irvin A.

The twelve tables in this study represent the results of a Fall 1975 survey of the 589 operating school districts in the State of New Jersey to determine the status of computer and data entry equipment utilization. Results show that the number of users of this equipment increased noticeably, primarily in administrative processing areas such as…

The application of automated operations at the Institutional Processing Center

NASA Technical Reports Server (NTRS)

Barr, Thomas H.

1993-01-01

The JPL Institutional and Mission Computing Division, Communications, Computing and Network Services Section, with its mission contractor, OAO Corporation, have for some time been applying automation to the operation of JPL's Information Processing Center (IPC). Automation does not come in one easy to use package. Automation for a data processing center is made up of many different software and hardware products supported by trained personnel. The IPC automation effort formally began with console automation, and has since spiraled out to include production scheduling, data entry, report distribution, online reporting, failure reporting and resolution, documentation, library storage, and operator and user education, while requiring the interaction of multi-vendor and locally developed software. To begin the process, automation goals are determined. Then a team including operations personnel is formed to research and evaluate available options. By acquiring knowledge of current products and those in development, taking an active role in industry organizations, and learning of other data center's experiences, a forecast can be developed as to what direction technology is moving. With IPC management's approval, an implementation plan is developed and resources identified to test or implement new systems. As an example, IPC's new automated data entry system was researched by Data Entry, Production Control, and Advance Planning personnel. A proposal was then submitted to management for review. A determination to implement the new system was made and elements/personnel involved with the initial planning performed the implementation. The final steps of the implementation were educating data entry personnel in the areas effected and procedural changes necessary to the successful operation of the new system.

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

Rudraswami, N. G.; Prasad, M. Shyam; Dey, S.

Most dust-sized cosmic particles undergo ablation and chemical alteration during atmospheric entry, which alters their original properties. A comprehensive understanding of this process is essential in order to decipher their pre-entry characteristics. The purpose of the study is to illustrate the process of vaporization of different elements for various entry parameters. The numerical results for particles of various sizes and various zenith angles are treated in order to understand the changes in chemical composition that the particles undergo as they enter the atmosphere. Particles with large sizes (> few hundred μ m) and high entry velocities (>16 km s{sup −1})more » experience less time at peak temperatures compared to those that have lower velocities. Model calculations suggest that particles can survive with an entry velocity of 11 km s{sup −1} and zenith angles (ZA) of 30°–90°, which accounts for ∼66% of the region where particles retain their identities. Our results suggest that the changes in chemical composition of MgO, SiO{sub 2}, and FeO are not significant for an entry velocity of 11 km s{sup −1} and sizes <300 μ m, but the changes in these compositions become significant beyond this size, where FeO is lost to a major extent. However, at 16 km s{sup −1} the changes in MgO, SiO{sub 2}, and FeO are very intense, which is also reflected in Mg/Si, Fe/Si, Ca/Si, and Al/Si ratios, even for particles with a size of 100 μ m. Beyond 400 μ m particle sizes at 16 km s{sup −1}, most of the major elements are vaporized, leaving the refractory elements, Al and Ca, suspended in the troposphere.« less

Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein

PubMed Central

Millet, Jean Kaoru; Whittaker, Gary R.

2014-01-01

Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly identified betacoronavirus causing high morbidity and mortality in humans. The coronavirus spike (S) protein is the main determinant of viral entry, and although it was previously shown that MERS-CoV S can be activated by various proteases, the details of the mechanisms of proteolytic activation of fusion are still incompletely characterized. Here, we have uncovered distinctive characteristics of MERS-CoV S. We identify, by bioinformatics and peptide cleavage assays, two cleavage sites for furin, a ubiquitously expressed protease, which are located at the S1/S2 interface and at the S2′ position of the S protein. We show that although the S1/S2 site is proteolytically processed by furin during protein biosynthesis, the S2′ site is cleaved upon viral entry. MERS-CoV pseudovirion infection was shown to be enhanced by elevated levels of furin expression, and entry could be decreased by furin siRNA silencing. Enhanced furin activity appeared to partially override the low pH-dependent nature of MERS-CoV entry. Inhibition of furin activity was shown to decrease MERS-CoV S-mediated entry, as well as infection by the virus. Overall, we show that MERS-CoV has evolved an unusual two-step furin activation for fusion, suggestive of a role during the process of emergence into the human population. The ability of MERS-CoV to use furin in this manner, along with other proteases, may explain the polytropic nature of the virus. PMID:25288733

Impact of Computerized Provider Order Entry on Pharmacist Productivity

PubMed Central

Hatfield, Mark D.; Cox, Rodney; Mhatre, Shivani K.; Flowers, W. Perry

2014-01-01

Abstract Purpose: To examine the impact of computerized provider order entry (CPOE) implementation on average time spent on medication order entry and the number of order actions processed. Methods: An observational time and motion study was conducted from March 1 to March 17, 2011. Two similar community hospital pharmacies were compared: one without CPOE implementation and the other with CPOE implementation. Pharmacists in the central pharmacy department of both hospitals were observed in blocks of 1 hour, with 24 hours of observation in each facility. Time spent by pharmacists on distributive, administrative, clinical, and miscellaneous activities associated with order entry were recorded using time and motion instrument documentation. Information on medication order actions and order entry/verifications was obtained using the pharmacy network system. Results: The mean ± SD time spent by pharmacists per hour in the CPOE pharmacy was significantly less than the non-CPOE pharmacy for distributive activities (43.37 ± 7.75 vs 48.07 ± 8.61) and significantly greater than the non-CPOE pharmacy for administrative (8.58 ± 5.59 vs 5.72 ± 6.99) and clinical (7.38 ± 4.27 vs 4.22 ± 3.26) activities. The CPOE pharmacy was associated with a significantly higher number of order actions per hour (191.00 ± 82.52 vs 111.63 ± 25.66) and significantly less time spent (in minutes per hour) on order entry and order verification combined (28.30 ± 9.25 vs 36.56 ± 9.14) than the non-CPOE pharmacy. Conclusion: The implementation of CPOE facilitated pharmacists to allocate more time to clinical and administrative functions and increased the number of order actions processed per hour, thus enhancing workflow efficiency and productivity of the pharmacy department. PMID:24958959

Old foes, new understandings: nuclear entry of small non-enveloped DNA viruses.

PubMed

Fay, Nikta; Panté, Nelly

2015-06-01

The nuclear import of viral genomes is an important step of the infectious cycle for viruses that replicate in the nucleus of their host cells. Although most viruses use the cellular nuclear import machinery or some components of this machinery, others have developed sophisticated ways to reach the nucleus. Some of these have been known for some time; however, recent studies have changed our understanding of how some non-enveloped DNA viruses access the nucleus. For example, parvoviruses enter the nucleus through small disruptions of the nuclear membranes and nuclear lamina, and adenovirus tugs at the nuclear pore complex, using kinesin-1, to disassemble their capsids and deliver viral proteins and genomes into the nucleus. Here we review recent findings of the nuclear import strategies of three small non-enveloped DNA viruses, including adenovirus, parvovirus, and the polyomavirus simian virus 40. Copyright © 2015 Elsevier B.V. All rights reserved.

Contaminated water delivery as a simple and effective method of experimental Salmonella infection

PubMed Central

O’Donnell, Hope; Pham, Oanh H.; Benoun, Joseph M.; Ravesloot-Chávez, Marietta M.; McSorley, Stephen J.

2016-01-01

Aims In most infectious disease models, it is assumed that gavage needle infection is the most reliable means of pathogen delivery to the gastrointestinal tract. However, this methodology can cause esophageal tearing and induces stress in experimental animals, both of which have the potential to impact early infection and the subsequent immune response. Materials and Methods C57BL/6 mice were orally infected with virulent Salmonella Typhimurium SL1344 either by intragastric gavage preceded by sodium bicarbonate, or by contamination of drinking water. Results We demonstrate that water contamination delivery of Salmonella is equivalent to gavage inoculation in providing a consistent model of infection. Furthermore, exposure of mice to contaminated drinking water for as little as 4 hours allowed maximal mucosal and systemic infection, suggesting an abbreviated window exists for natural intestinal entry. Conclusions Together, these data question the need for gavage delivery for infection with oral pathogens. PMID:26439708

Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II recepter HLA-DR1

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

Mullen, M.; Haan, K.M.; Longnecker, R.

Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes long-term latent infections, and is associated with a variety of human tumors. The EBV gp42 glycoprotein binds MHC class II molecules, playing a critical role in infection of B lymphocytes. EBV gp42 belongs to the C-type lectin superfamily, with homology to NK receptors of the immune system. We report the crystal structure of gp42 bound to the human MHC class II molecule HLA-DR1. The gp42 binds HLA-DR1 using a surface site that is distinct from the canonical lectin and NK receptor ligand binding sites. At the canonical ligand binding site, gp42 forms amore » large hydrophobic groove, which could interact with other ligands necessary for EBV entry, providing a mechanism for coupling MHC recognition and membrane fusion.« less

[Vaccinations and malaria prophylaxis for international travelers].

PubMed

Alberer, Martin; Löscher, Thomas

2015-05-01

The prevention of infectious diseases by vaccination and by counselling about malaria prophylaxis is a central aspect of travel medicine. Besides mandatory vaccinations required for entry to certain countries various vaccinations may be indicated depending on destination and type of travel as well as on individual risks of the traveler. In addition, pre-travel counselling should always include a check-up of standard vaccinations. Protection against mosquito bites is the basis of malaria prophylaxis. The addition of chemoprophylaxis is warranted in high risk areas. When regular chemoprophylaxis is not applied it is recommended to carry an appropriate antimalarial drug which can be used for emergency stand-by treatment in case of unexplained fever and when medical attention is not available within 24 hours. Travelers should realize that self-treatment is a first-aid measure and that they should still seek medical advice as soon as possible. © Georg Thieme Verlag KG Stuttgart · New York.

Chemokine-mediated immune responses in the female genital tract mucosa.

PubMed

Deruaz, Maud; Luster, Andrew D

2015-04-01

The genital tract mucosa is the site where sexually transmitted infections gain entry to the host. The immune response at this site is thus critical to provide innate protection against pathogens that are seen for the very first time as well as provide long-term pathogen-specific immunity, which would be required for an effective vaccine against sexually transmitted infection. A finely regulated immune response is therefore required to provide an effective barrier against pathogens without compromising the capacity of the genital tract to allow for successful conception and fetal development. We review recent developments in our understanding of the immune response in the female genital tract to infectious pathogens, using herpes simplex virus-2, human immunodeficiency virus-1 and Chlamydia trachomatis as examples, with a particular focus on the role of chemokines in orchestrating immune cell migration necessary to achieve effective innate and adaptive immune responses in the female genital tract.

Antitubercular Nucleosides that Inhibit Siderophore Biosynthesis: SAR of the Glycosyl Domain

PubMed Central

Somu, Ravindranadh V.; Wilson, Daniel; Bennett, Eric M.; Boshoff, Helena; Celia, Laura; Beck, Brian; Barry, Clifton E.; Aldrich, Courtney C.

2008-01-01

Tuberculosis (TB) is the leading cause of infectious disease mortality in the world by a bacterial pathogen. We previously demonstrated that a bisubstrate inhibitor of the adenylation enzyme MbtA, which is responsible for the second step of mycobactin biosynthesis, exhibited potent antitubercular activity. Here we systematically investigate the structure activity relationships of the bisubstrate inhibitor glycosyl domain resulting in the identification of a carbocyclic analogue that possesses a KIapp value of 2.3 nM and MIC99 values of 1.56 μM against M. tuberculosis H37Rv. The SAR data suggest the intriguing possibility that the bisubstrate inhibitors utilize a transporter for entry across the mycobacterial cell-envelope. Additionally, we report improved conditions for the expression of MbtA and biochemical analysis demonstrating that MbtA follows a random sequential enzyme mechanism for the adenylation half-reaction. PMID:17181146

Current Status of Messenger RNA Delivery Systems.

PubMed

Stanton, Matthew G

2018-06-01

Messenger RNA is emerging as a highly versatile biological construct for creation of impactful medicines. mRNA vaccines directed toward infectious disease and cancer are in clinical development with encouraging early reads on tolerability and efficacy. The use of mRNA to direct intense but transient expression of paracrine factors is finding utility in reprogramming progenitor cells for wound healing and cardiac regeneration and for stimulation of antitumor immune responses, at least preclinically as we await clinical results. The use of mRNA for prolonged and repeated expression of proteins and enzymes to treat rare, typically monogenic disease is nearing clinical entry. These uses of mRNA require delivery solutions, and the application of and improvement to existing nanoparticle nucleic acid delivery systems have jump started the pace of development and reenergized the field of particle based nucleic acid delivery. The current status of mRNA delivery is reviewed in this article with an eye toward clinical tractability.

Progress toward measles elimination in the People's Republic of China, 2000-2009.

PubMed

Ma, Chao; An, Zhijie; Hao, Lixin; Cairns, K Lisa; Zhang, Yan; Ma, Jing; Cao, Lei; Wen, Ning; Xu, Wenbo; Liang, Xiaofeng; Yang, Weizhong; Luo, Huiming

2011-07-01

In 2006, China set a goal of measles elimination by 2012. To describe progress toward this goal, we reviewed relevant policies and strategies and analyzed national data for 2000-2009. In response to implementation of these strategies, including increased routine measles vaccination coverage and province-specific supplementary immunization activities (SIAs), reported measles incidence decreased to a historically low level of 39.5 cases per million in 2009. A synchronized nationwide SIA was scheduled in 2010 to further decrease susceptibility to measles. However, reaching and maintaining measles elimination will require strong political commitment and efforts for strengthening surveillance, increasing 2-dose vaccine coverage to >95%, stricter enforcement of the requirement to check immunization status at school entry, and careful attention to measles susceptibility in those aged ≥15 years. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Contaminated water delivery as a simple and effective method of experimental Salmonella infection.

PubMed

O'Donnell, Hope; Pham, Oanh H; Benoun, Joseph M; Ravesloot-Chávez, Marietta M; McSorley, Stephen J

2015-01-01

In most infectious disease models, it is assumed that gavage needle infection is the most reliable means of pathogen delivery to the GI tract. However, this methodology can cause esophageal tearing and induces stress in experimental animals, both of which have the potential to impact early infection and the subsequent immune response. C57BL/6 mice were orally infected with virulent Salmonella Typhimurium SL1344 either by intragastric gavage preceded by sodium bicarbonate, or by contamination of drinking water. We demonstrate that water contamination delivery of Salmonella is equivalent to gavage inoculation in providing a consistent model of infection. Furthermore, exposure of mice to contaminated drinking water for as little as 4 h allowed maximal mucosal and systemic infection, suggesting an abbreviated window exists for natural intestinal entry. Together, these data question the need for gavage delivery for infection with oral pathogens.

Infectious Agents in Atherosclerotic Cardiovascular Diseases through Oxidative Stress

PubMed Central

Di Pietro, Marisa; Filardo, Simone; Falasca, Francesca; Turriziani, Ombretta; Sessa, Rosa

2017-01-01

Accumulating evidence demonstrates that vascular oxidative stress is a critical feature of atherosclerotic process, potentially triggered by several infectious agents that are considered as risk co-factors for the atherosclerotic cardiovascular diseases (CVDs). C. pneumoniae has been shown to upregulate multiple enzymatic systems capable of producing reactive oxygen species (ROS) such as NADPH oxidase (NOX) and cyclooxygenase in vascular endothelial cells, NOX and cytochrome c oxidase in macrophages as well as nitric oxide synthase and lipoxygenase in platelets contributing to both early and late stages of atherosclerosis. P. gingivalis seems to be markedly involved in the atherosclerotic process as compared to A. actinomycetemcomitans contributing to LDL oxidation and foam cell formation. Particularly interesting is the evidence describing the NLRP3 inflammasome activation as a new molecular mechanism underlying P. gingivalis-induced oxidative stress and inflammation. Amongst viral agents, immunodeficiency virus-1 and hepatitis C virus seem to have a major role in promoting ROS production, contributing, hence, to the early stages of atherosclerosis including endothelial dysfunction and LDL oxidation. In conclusion, oxidative mechanisms activated by several infectious agents during the atherosclerotic process underlying CVDs are very complex and not well-known, remaining, thus, an attractive target for future research. PMID:29156574

Infectious Agents in Atherosclerotic Cardiovascular Diseases through Oxidative Stress.

PubMed

Di Pietro, Marisa; Filardo, Simone; Falasca, Francesca; Turriziani, Ombretta; Sessa, Rosa

2017-11-18

Accumulating evidence demonstrates that vascular oxidative stress is a critical feature of atherosclerotic process, potentially triggered by several infectious agents that are considered as risk co-factors for the atherosclerotic cardiovascular diseases (CVDs). C. pneumoniae has been shown to upregulate multiple enzymatic systems capable of producing reactive oxygen species (ROS) such as NADPH oxidase (NOX) and cyclooxygenase in vascular endothelial cells, NOX and cytochrome c oxidase in macrophages as well as nitric oxide synthase and lipoxygenase in platelets contributing to both early and late stages of atherosclerosis. P. gingivalis seems to be markedly involved in the atherosclerotic process as compared to A. actinomycetemcomitans contributing to LDL oxidation and foam cell formation. Particularly interesting is the evidence describing the NLRP3 inflammasome activation as a new molecular mechanism underlying P. gingivalis -induced oxidative stress and inflammation. Amongst viral agents, immunodeficiency virus-1 and hepatitis C virus seem to have a major role in promoting ROS production, contributing, hence, to the early stages of atherosclerosis including endothelial dysfunction and LDL oxidation. In conclusion, oxidative mechanisms activated by several infectious agents during the atherosclerotic process underlying CVDs are very complex and not well-known, remaining, thus, an attractive target for future research.

Inhibitors of SARS-CoV Entry - Identification using an Internally-Controlled Dual Envelope Pseudovirion Assay

PubMed Central

Zhou, Yanchen; Agudelo, Juliet; Lu, Kai; Goetz, David H.; Hansell, Elizabeth; Chen, Yen Ting; Roush, William R.; McKerrow, James; Craik, Charles S.; Amberg, Sean M.; Simmons, Graham

2011-01-01

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged as the causal agent of an endemic atypical pneumonia, infecting thousands of people worldwide. Although a number of promising potential vaccines and therapeutic agents for SARS-CoV have been described, no effective antiviral drug against SARS-CoV is currently available. The intricate, sequential nature of the viral entry process provides multiple valid targets for drug development. Here, we describe a rapid and safe cell-based high-throughput screening system, Dual Envelope Pseudovirion (DEP) Assay, for specifically screening inhibitors of viral entry. The assay system employs a novel dual envelope strategy, using lentiviral pseudovirions as targets whose entry is driven by the SARS-CoV Spike glycoprotein. A second, unrelated viral envelope is used as an internal control to reduce the number of false positives. As an example of the power of this assay a class of inhibitors is reported with the potential to inhibit SARS-CoV at two steps of the replication cycle, viral entry and particle assembly. This assay system can be easily adapted to screen entry inhibitors against other viruses with the careful selection of matching partner virus envelopes. PMID:21820471

Knowledge information management toolkit and method

DOEpatents

Hempstead, Antoinette R.; Brown, Kenneth L.

2006-08-15

A system is provided for managing user entry and/or modification of knowledge information into a knowledge base file having an integrator support component and a data source access support component. The system includes processing circuitry, memory, a user interface, and a knowledge base toolkit. The memory communicates with the processing circuitry and is configured to store at least one knowledge base. The user interface communicates with the processing circuitry and is configured for user entry and/or modification of knowledge pieces within a knowledge base. The knowledge base toolkit is configured for converting knowledge in at least one knowledge base from a first knowledge base form into a second knowledge base form. A method is also provided.

Bibliography of atomic and molecular processes. Volume 1, 1978-1981

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

Barnett, C.F.; Crandall, D.H.; Farmer, B.J.

1982-10-01

This annotated bibliography lists 10,676 works on atomic and molecular processes reported in publications dated 1978-1981. Sources include scientific journals, conference proceedings, and books. Each entry is designated by one or more of the 114 categories of atomic and molecular processes used by the Controlled Fusion Atomic Data Center, Oak Ridge National Laboratory to classify data. Also indicated is whether the work was experimental or theoretical, what energy range was covered, what reactants were investigated, and the county of origin of the first author. Following the bibliographical listing, the entries are indexed according to the categories and according to reactantsmore » within each subcategory.« less

ELECTRA © Launch and Re-Entry Safety Analysis Tool

NASA Astrophysics Data System (ADS)

Lazare, B.; Arnal, M. H.; Aussilhou, C.; Blazquez, A.; Chemama, F.

2010-09-01

French Space Operation Act gives as prime objective to National Technical Regulations to protect people, properties, public health and environment. In this frame, an independent technical assessment of French space operation is delegated to CNES. To perform this task and also for his owns operations CNES needs efficient state-of-the-art tools for evaluating risks. The development of the ELECTRA© tool, undertaken in 2007, meets the requirement for precise quantification of the risks involved in launching and re-entry of spacecraft. The ELECTRA© project draws on the proven expertise of CNES technical centers in the field of flight analysis and safety, spaceflight dynamics and the design of spacecraft. The ELECTRA© tool was specifically designed to evaluate the risks involved in the re-entry and return to Earth of all or part of a spacecraft. It will also be used for locating and visualizing nominal or accidental re-entry zones while comparing them with suitable geographic data such as population density, urban areas, and shipping lines, among others. The method chosen for ELECTRA© consists of two main steps: calculating the possible reentry trajectories for each fragment after the spacecraft breaks up; calculating the risks while taking into account the energy of the fragments, the population density and protection afforded by buildings. For launch operations and active re-entry, the risk calculation will be weighted by the probability of instantaneous failure of the spacecraft and integrated for the whole trajectory. ELECTRA©’s development is today at the end of the validation phase, last step before delivery to users. Validation process has been performed in different ways: numerical application way for the risk formulation; benchmarking process for casualty area, level of energy of the fragments entries and level of protection housing module; best practices in space transportation industries concerning dependability evaluation; benchmarking process for world population repartition leading to the choice of a worldwide used model called GPW V3. Then, the complementary part for validation has been numerous system tests, most of them by comparison with already existing tools, operationally used for example into the European Space port in French Guyana. The purpose of this article is to review the method and models chosen by CNES for describing physical phenomena and the results of validation process including comparison with other risk assessment tools.

Scratch2 prevents cell cycle re-entry by repressing miR-25 in postmitotic primary neurons.

PubMed

Rodríguez-Aznar, Eva; Barrallo-Gimeno, Alejandro; Nieto, M Angela

2013-03-20

During the development of the nervous system the regulation of cell cycle, differentiation, and survival is tightly interlinked. Newly generated neurons must keep cell cycle components under strict control, as cell cycle re-entry leads to neuronal degeneration and death. However, despite their relevance, the mechanisms controlling this process remain largely unexplored. Here we show that Scratch2 is involved in the control of the cell cycle in neurons in the developing spinal cord of the zebrafish embryo. scratch2 knockdown induces postmitotic neurons to re-enter mitosis. Scratch2 prevents cell cycle re-entry by maintaining high levels of the cycle inhibitor p57 through the downregulation of miR-25. Thus, Scratch2 appears to safeguard the homeostasis of postmitotic primary neurons by preventing cell cycle re-entry.

Early detection and response for measles and rubella cases through the (Nursery) School Absenteeism Surveillance System in Ibaraki Prefecture.

PubMed

Watanabe, Miki; Kurita, Junko; Takagi, Takeshi; Nagata, Noriko; Nagasu, Natsuki; Sugawara, Tamie; Ohkusa, Yasushi

2016-01-01

Objectives In Ibaraki Prefecture, all (nursery) schools have joined the (Nursery) School Absenteeism Surveillance System (hereafter denoted as (N)SASSy), which is operated by the Japan School Health Association to monitor the prevalence of infectious diseases, the early detection and response for outbreaks, and prevention of large outbreaks. Prefectural government officers also utilize it as a control measure for infectious diseases. In particular, when cases of measles or rubella are registered, (N)SASSy sends e-mails automatically to prefectural government officers to activate control measures. This paper summarizes administrative responses by prefectural government officers for measles or rubella cases using (N)SASSy and discusses the future challenges.Methods We summarized registration, detection, and first response data for measles or rubella cases in (N)SASSy and compared the number of detected and reported cases enforced by the Infectious Diseases Control Law from January 1, 2013 to December 31, 2014.Results The public health center questioned hospitals/clinics and (nursery) schools about all registered measles or rubella cases in (N)SASSy on the same day to check the entered information. In the past 2 years, there were 5 measles and 56 rubella cases in 2013 and 1 measles and 19 rubella cases in 2014 registered with (N)SASSy. All cases were checked and investigated by the public health center. Of all cases detected by (N)SASSy, 7 rubella cases in 2013 and 1 rubella case in 2014 were reported based on the law. No measles cases were reported in the 2 years. The results of investigations and laboratory tests were given as feedback to the (nursery) schools. If the case did not case definition determined by the law, we changed the status in (N)SASSy to suspected or discarded cases.Conclusion Since (N)SASSy assists prefectural government officers with earlier detection of and response for infectious diseases, it definitely contributes to infection control. Immediate feedback of the laboratory test results to the (nursery) schools was also useful to confirm cases of measles or rubella. As data entry in (nursery) schools is needed for stable operation and utilization of (N)SASSy, it is important that workshops for (N)SASSy are held for (nursery) school teachers every year to maintain accuracy. Our future challenges include the coordination among (nursery) schools, hospitals/clinics, and prefectural government and their applications for infection control.

Optometrists Association Australia Universal (entry-level) and Therapeutic Competency Standards for Optometry 2008.

PubMed

Kiely, Patricia M

2009-07-01

Competency standards for entry-level to the profession of optometry in Australia were first developed in 1993, revised in 1997 and expanded in 2000 to include therapeutic competency standards. The entry-level standards cover the competencies required by a person entering the profession without therapeutic endorsement of their registration. The therapeutic competency standards address the additional competencies required for therapeutic endorsement of registration. This paper presents a revised version of the universal (entry-level) and therapeutic competency standards for the profession of optometry in Australia in 2008. Expert members of the profession and representatives from schools of optometry, registration boards in Australia, state divisions of Optometrists Association Australia and the New Zealand Association of Optometrists were consulted in the process of updating the standards. Three new elements of competency have been added to the standards. Twenty-three new performance criteria with associated indicators have been added. Some performance criteria from the earlier document have been combined. Substantial alterations were made to the presentation of indicators throughout the document. The updated entry-level (universal) and therapeutic competency standards were adopted on behalf of the profession by the National Council of Optometrists Association Australia in November 2008. Competency standards are used by Australian and New Zealand registration authorities for the purposes of registration and therapeutic endorsement of registration via the Optometry Council of Australia and New Zealand accreditation and assessment processes. They have also been used as the basis of the World Council of Optometry Global Competency-Based Model.

A parallel genome-wide RNAi screening strategy to identify host proteins important for entry of Marburg virus and H5N1 influenza virus.

PubMed

Cheng, Han; Koning, Katie; O'Hearn, Aileen; Wang, Minxiu; Rumschlag-Booms, Emily; Varhegyi, Elizabeth; Rong, Lijun

2015-11-24

Genome-wide RNAi screening has been widely used to identify host proteins involved in replication and infection of different viruses, and numerous host factors are implicated in the replication cycles of these viruses, demonstrating the power of this approach. However, discrepancies on target identification of the same viruses by different groups suggest that high throughput RNAi screening strategies need to be carefully designed, developed and optimized prior to the large scale screening. Two genome-wide RNAi screens were performed in parallel against the entry of pseudotyped Marburg viruses and avian influenza virus H5N1 utilizing an HIV-1 based surrogate system, to identify host factors which are important for virus entry. A comparative analysis approach was employed in data analysis, which alleviated systematic positional effects and reduced the false positive number of virus-specific hits. The parallel nature of the strategy allows us to easily identify the host factors for a specific virus with a greatly reduced number of false positives in the initial screen, which is one of the major problems with high throughput screening. The power of this strategy is illustrated by a genome-wide RNAi screen for identifying the host factors important for Marburg virus and/or avian influenza virus H5N1 as described in this study. This strategy is particularly useful for highly pathogenic viruses since pseudotyping allows us to perform high throughput screens in the biosafety level 2 (BSL-2) containment instead of the BSL-3 or BSL-4 for the infectious viruses, with alleviated safety concerns. The screening strategy together with the unique comparative analysis approach makes the data more suitable for hit selection and enables us to identify virus-specific hits with a much lower false positive rate.

Global Foot-and-Mouth Disease Research Update and Gap Analysis: 7 - Pathogenesis and Molecular Biology.

PubMed

Robinson, L; Knight-Jones, T J D; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

2016-06-01

We assessed research knowledge gaps in the fields of FMDV (foot-and-mouth disease virus) pathogenesis and molecular biology by performing a literature review (2011-15) and collecting research updates (2014) from 33 institutes from across the world. Findings were used to identify priority areas for future research. There have been important advances in FMDV pathogenesis; FMDV remains in lymph nodes of many recovered animals that otherwise do not appear persistently infected, even in species previously not associated with the carrier state. Whether virus retention helps maintain host immunity and/or virus survival is not known. Studies of FMDV pathogenesis in wildlife have provided insights into disease epidemiology, in endemic and epidemic settings. Many aspects of FMDV infection and virus entry remain unknown; however, at the cellular level, we know that expression level and availability of integrins (that permit viral entry), rate of clearance of infected cells and strength of anti-viral type I IFN (interferon) response are key determinants of tissue tropism. Extending findings to improved understanding of transmission requires a standardized approach and adoption of natural routes of infection during experimental study. There has been recognition of the importance of autophagosomes for FMDV entry into the cytoplasm following cell surface receptor binding, and that distinct internal cellular membranes are exploited for viral replication and immune evasion. New roles for viral proteins in blocking type I IFN production and downstream signalling have been identified facilitating research in anti-viral therapeutics. We know more about how infection affects cell protein expression, and research into molecular determinants of capsid stability has aided the development of stable vaccines. We have an expanding knowledge of viral and host molecular determinates of virulence and infectiousness, and of how phylogenetics may be used to estimate vaccine match and strain distribution. With ongoing advances, these areas could translate into significantly improved disease control. © 2016 Blackwell Verlag GmbH.

From micro to mainframe. A practical approach to perinatal data processing.

PubMed

Yeh, S Y; Lincoln, T

1985-04-01

A new, practical approach to perinatal data processing for a large obstetric population is described. This was done with a microcomputer for data entry and a mainframe computer for data reduction. The Screen Oriented Data Access (SODA) program was used to generate the data entry form and to input data into the Apple II Plus computer. Data were stored on diskettes and transmitted through a modern and telephone line to the IBM 370/168 computer. The Statistical Analysis System (SAS) program was used for statistical analyses and report generations. This approach was found to be most practical, flexible, and economical.

Parallel pulse processing and data acquisition for high speed, low error flow cytometry

DOEpatents

Engh, G.J. van den; Stokdijk, W.

1992-09-22

A digitally synchronized parallel pulse processing and data acquisition system for a flow cytometer has multiple parallel input channels with independent pulse digitization and FIFO storage buffer. A trigger circuit controls the pulse digitization on all channels. After an event has been stored in each FIFO, a bus controller moves the oldest entry from each FIFO buffer onto a common data bus. The trigger circuit generates an ID number for each FIFO entry, which is checked by an error detection circuit. The system has high speed and low error rate. 17 figs.

Lander Trajectory Reconstruction computer program

NASA Technical Reports Server (NTRS)

Adams, G. L.; Bradt, A. J.; Ferguson, J. B.; Schnelker, H. J.

1971-01-01

The Lander Trajectory Reconstruction (LTR) computer program is a tool for analysis of the planetary entry trajectory and atmosphere reconstruction process for a lander or probe. The program can be divided into two parts: (1) the data generator and (2) the reconstructor. The data generator provides the real environment in which the lander or probe is presumed to find itself. The reconstructor reconstructs the entry trajectory and atmosphere using sensor data generated by the data generator and a Kalman-Schmidt consider filter. A wide variety of vehicle and environmental parameters may be either solved-for or considered in the filter process.

Infectious particles, stress, and induced prion amyloids

PubMed Central

2013-01-01

Transmissible encephalopathies (TSEs) are believed by many to arise by spontaneous conversion of host prion protein (PrP) into an infectious amyloid (PrP-res, PrPSc) without nucleic acid. Many TSE agents reside in the environment, with infection controlled by public health measures. These include the disappearance of kuru with the cessation of ritual cannibalism, the dramatic reduction of epidemic bovine encephalopathy (BSE) by removal of contaminated feed, and the lack of endemic scrapie in geographically isolated Australian sheep with susceptible PrP genotypes. While prion protein modeling has engendered an intense focus on common types of protein misfolding and amyloid formation in diverse organisms and diseases, the biological characteristics of infectious TSE agents, and their recognition by the host as foreign entities, raises several fundamental new directions for fruitful investigation such as: (1) unrecognized microbial agents in the environmental metagenome that may cause latent neurodegenerative disease, (2) the evolutionary social and protective functions of different amyloid proteins in diverse organisms from bacteria to mammals, and (3) amyloid formation as a beneficial innate immune response to stress (infectious and non-infectious). This innate process however, once initiated, can become unstoppable in accelerated neuronal aging. PMID:23633671

Development of a pathway model to assess the exposure of European pine trees to pine wood nematode via the trade of wood.

PubMed

Douma, J C; van der Werf, W; Hemerik, L; Magnusson, C; Robinet, C

2017-04-01

Pine wood nematode (PWN), Bursaphelenchus xylophilus, is a threat for pine species (Pinus spp.) throughout the world. The nematode is native to North America, and invaded Japan, China, Korea, and Taiwan, and more recently Portugal and Spain. PWN enters new areas through trade in wood products. Once established, eradication is not practically feasible. Therefore, preventing entry of PWN into new areas is crucial. Entry risk analysis can assist in targeting management to reduce the probability of entry. Assessing the entry of PWN is challenging due to the complexity of the wood trade and the wood processing chain. In this paper, we develop a pathway model that describes the wood trade and wood processing chain to determine the structure of the entry process. We consider entry of PWN through imported coniferous wood from China, a possible origin of Portuguese populations, to Europe. We show that exposure increased over years due to an increase in imports of sawn wood. From 2000 to 2012, Europe received an estimated 84 PWN propagules from China, 88% of which arose from imported sawn wood and 12% from round wood. The region in Portugal where the PWN was first reported is among those with the highest PWN transfer per unit of imported wood due to a high host cover and vector activity. An estimated 62% of PWN is expected to enter in countries where PWN is not expected to cause the wilt of pine trees because of low summer temperatures (e.g., Belgium, Sweden, Norway). In these countries, PWN is not easily detected, and such countries can thus serve as potential reservoirs of PWN. The model identifies ports and regions with high exposure, which helps targeting monitoring and surveillance, even in areas where wilt disease is not expected to occur. In addition, we show that exposure is most efficiently reduced by additional treatments in the country of origin, and/or import wood from PWN-free zones. Pathway modelling assists plant health managers in analyzing risks along the pathway and planning measures for enhancing biosecurity. © 2016 by the Ecological Society of America.

Optimizing the user interface of a data entry module for an electronic patient record for cardiac rehabilitation: A mixed method usability approach.

PubMed

van Engen-Verheul, Mariëtte M; Peute, Linda W P; de Keizer, Nicolette F; Peek, Niels; Jaspers, Monique W M

2016-03-01

Cumbersome electronic patient record (EPR) interfaces may complicate data-entry in clinical practice. Completeness of data entered in the EPR determines, among other things, the value of computerized clinical decision support (CCDS). Quantitative usability evaluations can provide insight into mismatches between the system design model of data entry and users' data entry behavior, but not into the underlying causes for these mismatches. Mixed method usability evaluation studies may provide these insights, and thus support generating redesign recommendations for improving an EPR system's data entry interface. To improve the usability of the data entry interface of an EPR system with CCDS in the field of cardiac rehabilitation (CR), and additionally, to assess the value of a mixed method usability approach in this context. Seven CR professionals performed a think-aloud usability evaluation both before (beta-version) and after the redesign of the system. Observed usability problems from both evaluations were analyzed and categorized using Zhang et al.'s heuristic principles of good interface design. We combined the think-aloud usability evaluation of the system's beta-version with the measurement of a new usability construct: users' deviations in action sequence from the system's predefined data entry order sequence. Recommendations for redesign were implemented. We assessed whether the redesign improved CR professionals' (1) task efficacy (with respect to the completeness of data they collected), and (2) task efficiency (with respect to the average number of mouse clicks they needed to complete data entry subtasks). With the system's beta version, 40% of health care professionals' navigation actions through the system deviated from the predefined next system action. The causes for these deviations as revealed by the think-aloud method mostly concerned mismatches between the system design model for data entry action sequences and users expectations of these action sequences, based on their paper-based daily routines. This caused non completion of data entry tasks (31% of main tasks completed), and more navigation actions than minimally required (146% of the minimum required). In the redesigned system the data entry navigational structure was organized in a flexible way around an overview screen to better mimic users' paper-based daily routines of collecting patient data. This redesign resulted in an increased number of completed main tasks (70%) and a decrease in navigation actions (133% of the minimum required). The think-aloud usability evaluation of the redesigned system showed that remaining problems concerned flexibility (e.g., lack of customization options) and consistency (mainly with layout and position of items on the screen). The mixed method usability evaluation was supportive in revealing the magnitude and causes of mismatches between the system design model of data-entry with users' data entry behavior. However, as both task efficacy and efficiency were still not optimal with the redesigned EPR, we advise to perform a cognitive analysis on end users' mental processes and behavior patterns in daily work processes specifically during the requirements analysis phase of development of interactive healthcare information systems. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Open access tools for quality-assured and efficient data entry in a large, state-wide tobacco survey in India.

PubMed

Shewade, Hemant Deepak; Vidhubala, E; Subramani, Divyaraj Prabhakar; Lal, Pranay; Bhatt, Neelam; Sundaramoorthi, C; Singh, Rana J; Kumar, Ajay M V

2017-01-01

A large state-wide tobacco survey was conducted using modified version of pretested, globally validated Global Adult Tobacco Survey (GATS) questionnaire in 2015-22016 in Tamil Nadu, India. Due to resource constrains, data collection was carrid out using paper-based questionnaires (unlike the GATS-India, 2009-2010, which used hand-held computer devices) while data entry was done using open access tools. The objective of this paper is to describe the process of data entry and assess its quality assurance and efficiency. In EpiData language, a variable is referred to as 'field' and a questionnaire (set of fields) as 'record'. EpiData software was used for double data entry with adequate checks followed by validation. Teamviewer was used for remote training and trouble shooting. The EpiData databases (one each for each district and each zone in Chennai city) were housed in shared Dropbox folders, which enabled secure sharing of files and automatic back-up. Each database for a district/zone had separate file for data entry of household level and individual level questionnaire. Of 32,945 households, there were 111,363 individuals aged ≥15 years. The average proportion of records with data entry errors for a district/zone in household level and individual level file was 4% and 24%, respectively. These are the errors that would have gone unnoticed if single entry was used. The median (inter-quartile range) time taken for double data entry for a single household level and individual level questionnaire was 30 (24, 40) s and 86 (64, 126) s, respectively. Efficient and quality-assured near-real-time data entry in a large sub-national tobacco survey was performed using innovative, resource-efficient use of open access tools.

Hepatitis C virus depends on E-cadherin as an entry factor and regulates its expression in epithelial-to-mesenchymal transition.

PubMed

Li, Qisheng; Sodroski, Catherine; Lowey, Brianna; Schweitzer, Cameron J; Cha, Helen; Zhang, Fang; Liang, T Jake

2016-07-05

Hepatitis C virus (HCV) enters the host cell through interactions with a cascade of cellular factors. Although significant progress has been made in understanding HCV entry, the precise mechanisms by which HCV exploits the receptor complex and host machinery to enter the cell remain unclear. This intricate process of viral entry likely depends on additional yet-to-be-defined cellular molecules. Recently, by applying integrative functional genomics approaches, we identified and interrogated distinct sets of host dependencies in the complete HCV life cycle. Viral entry assays using HCV pseudoparticles (HCVpps) of various genotypes uncovered multiple previously unappreciated host factors, including E-cadherin, that mediate HCV entry. E-cadherin silencing significantly inhibited HCV infection in Huh7.5.1 cells, HepG2/miR122/CD81 cells, and primary human hepatocytes at a postbinding entry step. Knockdown of E-cadherin, however, had no effect on HCV RNA replication or internal ribosomal entry site (IRES)-mediated translation. In addition, an E-cadherin monoclonal antibody effectively blocked HCV entry and infection in hepatocytes. Mechanistic studies demonstrated that E-cadherin is closely associated with claudin-1 (CLDN1) and occludin (OCLN) on the cell membrane. Depletion of E-cadherin drastically diminished the cell-surface distribution of these two tight junction proteins in various hepatic cell lines, indicating that E-cadherin plays an important regulatory role in CLDN1/OCLN localization on the cell surface. Furthermore, loss of E-cadherin expression in hepatocytes is associated with HCV-induced epithelial-to-mesenchymal transition (EMT), providing an important link between HCV infection and liver cancer. Our data indicate that a dynamic interplay among E-cadherin, tight junctions, and EMT exists and mediates an important function in HCV entry.

Quality Assessment of Process Measures in Antimicrobial Stewardship: Concordance of Valacyclovir Indication and Automatic Prospective Approval in Computerized Provider Order Entry

PubMed Central

Lee, Tiffany; McCoy, Christopher; Mahoney, Monica V

2017-01-01

Abstract Background The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) recommend computerized decision support at the time of prescribing as an antimicrobial stewardship (AST) tool. Providing antimicrobial indications during prescribing can optimize infection-specific therapy through appropriate antimicrobial selection, dosing, and frequency. The Leapfrog group identifies this as a quality measure for their report card system. At Beth Israel Deaconess Medical Center (BIDMC), indication-based dosing has been incorporated in the computerized provider order entry (CPOE) system since 2006. At BIDMC, valacyclovir is only approved for the treatment of varicella zoster (VZV) infection or prophylaxis of solid organ transplant (SOT) patients at low risk for cytomegalovirus. These indications bypass the need for AST approval. Accuracy validation of the selected indications has not been formally performed. Methods A retrospective chart review was performed in patients prescribed valacyclovir during an 8-month period in 2016. Electronic medical records, laboratory reports, and pharmacy records were reviewed to identify the suspected/confirmed infection. The primary outcome was the concordance rate of selected CPOE valacyclovir indication compared with suspected/confirmed infection at the time of ordering. The secondary outcome was the proportion of valacyclovir use per institutional protocol. Results Overall, 117 patients were included, with a median age of 57.9 years, 51 (43.6%) were male, and 4 (3.4%) were located in an intensive care unit. Fifty-nine orders (50.4%) selected VZV as the indication, followed by 21 orders (17.9%) for SOT prophylaxis. Of orders with any CPOE indication, only 59/101 (58.4%) were concordant with suspected/confirmed infection. Of the valacyclovir orders with a VZV indication, 37 (62.7%) were concordant. Of the orders with SOT prophylaxis indications, 5 (23.8%) were concordant. Furthermore, only 46 orders (39.3%) were per BIDMC-protocol. Conclusion Concordance of CPOE indication selection and suspected/confirmed infection for valacyclovir was low. Using CPOE to grant automatic prospective approval must be monitored and audited for accuracy if employed as an AST tool. Disclosures All authors: No reported disclosures.

[Tetanus in neonates and women of child-bearing age in the Dakar hospital infectious diseases unit].

PubMed

Manga, N M; Dia, N M; Ndour, C T; Diop, S A; Fortes, L; Mbaye, M; Diop, B M; Sow, P S

2009-12-01

This study had for aim to describe and compare the epidemiological, clinical and outcome features of tetanus in neonates (NT) and women of child bearing age (WCBAT) in Dakar. This retrospective study was made on NT (3 to 28 days of age) and WCBAT (15 to 49 years of age) patient files, admitted in the Fann University Hospital Infectious Diseases Clinic from 2000 to 2007. One hundred and thirty-eight WCBAT (11.9%) and 103 NT (8.9%), for a total of 1156 cases of tetanus were admitted. A decrease of the annual rate of these populations was noted over this 8 year period. The majority (59.4%) of WCBAT was between 15 and 25 years of age and the mean age of NT was 9.3 days. Most of the patients in both groups came from suburban areas (78%). The tetanus immunization status was not updated for 92% of WCBAT. The most frequent portals of entry were cutaneous wounds for WCBAT (77.4%) and umbilical stumps for NT (85.4%). On admission, 64% of NT presented with severe tetanus (stage III on the Mollaret scale) compared to 11.6% for WCBAT. The death rate was significantly higher in NT (48.5%) than in WCBAT (26.8%); p=0.0005. To eliminate neonatal tetanus, the prognosis of which is worse in Dakar, an intensification of the large vaccination program is needed with supplementary vaccination campaigns including women of child bearing age in areas of risk.

An atypical genotype of Toxoplasma gondii as a cause of mortality in Hector's dolphins (Cephalorhynchus hectori).

PubMed

Roe, W D; Howe, L; Baker, E J; Burrows, L; Hunter, S A

2013-02-18

Hector's dolphins (Cephalorhynchus hectori) are a small endangered coastal species that are endemic to New Zealand. Anthropogenic factors, particularly accidental capture in fishing nets, are believed to be the biggest threat to survival of this species. The role of infectious disease as a cause of mortality has not previously been well investigated. This study investigates Toxoplasma gondii infection in Hector's dolphins, finding that 7 of 28 (25%) dolphins examined died due to disseminated toxoplasmosis, including 2 of 3 Maui's dolphins, a critically endangered sub-species. A further 10 dolphins had one or more tissues that were positive for the presence of T. gondii DNA using PCR. Genotyping revealed that 7 of 8 successfully amplified isolates were an atypical Type II genotype. Fatal cases had necrotising and haemorrhagic lesions in the lung (n=7), lymph nodes (n=6), liver (n=4) and adrenals (n=3). Tachyzoites and tissue cysts were present in other organs including the brain (n=5), heart (n=1), stomach (n=1) and uterus (n=1) with minimal associated inflammatory response. One dolphin had a marked suppurative metritis in the presence of numerous intra-epithelial tachyzoites. No dolphins had underlying morbillivirus infection. This study provides the first evidence that infectious agents could be important in the population decline of this species, and highlights the need for further research into the route of entry of T. gondii organisms into the marine environment worldwide. Copyright © 2012 Elsevier B.V. All rights reserved.

Restriction by APOBEC3 proteins of endogenous retroviruses with an extracellular life cycle: ex vivo effects and in vivo "traces" on the murine IAPE and human HERV-K elements

PubMed Central

Esnault, Cécile; Priet, Stéphane; Ribet, David; Heidmann, Odile; Heidmann, Thierry

2008-01-01

Background APOBEC3 cytosine deaminases have been demonstrated to restrict infectivity of a series of retroviruses, with different efficiencies depending on the retrovirus. In addition, APOBEC3 proteins can severely restrict the intracellular transposition of a series of retroelements with a strictly intracellular life cycle, including the murine IAP and MusD LTR-retrotransposons. Results Here we show that the IAPE element, which is the infectious progenitor of the strictly intracellular IAP elements, and the infectious human endogenous retrovirus HERV-K are restricted by both murine and human APOBEC3 proteins in an ex vivo assay for infectivity, with evidence in most cases of strand-specific G-to-A editing of the proviruses, with the expected signatures. In silico analysis of the naturally occurring genomic copies of the corresponding endogenous elements performed on the mouse and human genomes discloses "traces" of APOBEC3-editing, with the specific signature of the murine APOBEC3 and human APOBEC3G enzymes, respectively, and to a variable extent depending on the family member. Conclusion These results indicate that the IAPE and HERV-K elements, which can only replicate via an extracellular infection cycle, have been restricted at the time of their entry, amplification and integration into their target host genomes by definite APOBEC3 proteins, most probably acting in evolution to limit the mutagenic effect of these endogenized extracellular parasites. PMID:18702815

Enhanced in vivo targeting of murine nonparenchymal liver cells with monophosphoryl lipid A functionalized microcapsules.

PubMed

Pietrzak-Nguyen, Anette; Fichter, Michael; Dedters, Marvin; Pretsch, Leah; Gregory, Stephen H; Meyer, Claudius; Doganci, Aysefa; Diken, Mustafa; Landfester, Katharina; Baier, Grit; Gehring, Stephan

2014-07-14

A broad spectrum of infectious liver diseases emphasizes the need of microparticles for targeted delivery of immunomodulatory substances to the liver. Microcapsules (MCs) are particularly attractive for innovative drug and vaccine formulations, enabling the combination of antigen, drugs, and adjuvants. The present study aimed to develop microcapsules characterized by an enhanced liver deposition and accelerated uptake by nonparenchymal liver cells (NPCs). Initially, two formulations of biodegradable microcapsules were synthesized from either hydroxyethyl starch (HES) or mannose. Notably, HES-MCs accumulated primarily in the liver, while mannose particles displayed a lung preference. Functionalization of HES-MCs with anti-CD40, anti-DEC205, and/or monophosphoryl lipid A (MPLA) enhanced uptake of MCs by nonparenchymal liver cells in vitro. In contrast, only MPLA-coated HES-MCs promoted significantly the in vivo uptake by NPCs. Finally, HES-MCs equipped with MPLA, anti-CD40, and anti-DEC205 induced the secretion of TNF-α, IL-6 by Kupffer cells (KCs), and IFN-γ and IL-12p70 by liver dendritic cells (DCs). The enhanced uptake and activation of KCs by MPLA-HES-MCs is a promising approach to prevent or treat infection, since KCs are exploited as an entry gate in various infectious diseases, such as malaria. In parallel, loading and activating liver DCs, usually prone to tolerance, bears the potential to induce antigen specific, intrahepatic immune responses necessary to prevent and treat infections affecting the liver.

Modulation of iridovirus-induced apoptosis by endocytosis, early expression, JNK, and apical caspase

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

Chitnis, Nilesh S.; D'Costa, Susan M.; Paul, Eric R.

Chilo iridescent virus (CIV) is the type species for the family Iridoviridae, which are large, isometric, cytoplasmic dsDNA viruses. We examined the mechanism of apoptosis induction by CIV. High CIV doses (CIV{sub XS}; 400 {mu}g/ml), UV-irradiated virus (CIV{sub UV}; 10 {mu}g/ml) and CVPE (CIV protein extract; 10 {mu}g/ml) induced apoptosis in 60% of treated Choristoneura fumiferana (IPRI-CF-124T) cells. Normal doses of infectious CIV (10 {mu}g/ml) induced apoptosis in only 10% of C. fumiferana (CF) cells. Apoptosis was inhibited by Z-IETD-FMK, an apical caspase inhibitor, indicating that CIV-induced apoptosis requires caspase activity. The putative caspase in CF cells was designated Cf-caspase-i.more » CIV{sub UV} or CVPE enhanced Cf-caspase-i activity by 80% at 24 h relative to mock-treated cells. Since the MAP kinase pathway induces or inhibits apoptosis depending on the context, we used JNK inhibitor SP600125 and demonstrated drastic suppression of CVPE-induced apoptosis. Thus, the JNK signaling pathway is significant for apoptosis in this system. Virus interaction with the cell surface was not sufficient for apoptosis since CIV{sub UV} particles bound to polysterene beads failed to induce apoptosis. Endocytosis inhibitors (bafilomycin or ammonium chloride) negated apoptosis induction by CIV{sub UV}, CIV{sub XS} or CVPE indicating that entry through this mode is required. Given the weak apoptotic response to infectious CIV, we postulated that viral gene expression inhibited apoptosis. CIV infection of cells pretreated with cycloheximide induced apoptosis in 69% of the cells compared to 10% in normal infections. Furthermore, blocking viral DNA replication with aphidicolin or phosphonoacetic acid suppressed apoptosis and Cf-caspase-i activity, indicating that early viral expression is necessary for inhibition of apoptosis, and de novo synthesis of viral proteins is not required for induction. We show for the first time that, in a member of the family Iridoviridae, apoptosis: (i) requires entry and endocytosis of virions or virion proteins, (ii) is inhibited under conditions permitting early viral expression, and (iii) requires the JNK signaling pathway. This is the first report of JNK signal requirement during apoptosis induction by an insect virus.« less

Attorney General forces Infectious Diseases Society of America to redo Lyme guidelines due to flawed development process.

PubMed

Johnson, L; Stricker, R B

2009-05-01

Lyme disease is one of the most controversial illnesses in the history of medicine. In 2006 the Connecticut Attorney General launched an antitrust investigation into the Lyme guidelines development process of the Infectious Diseases Society of America (IDSA). In a recent settlement with IDSA, the Attorney General noted important commercial conflicts of interest and suppression of scientific evidence that had tainted the guidelines process. This paper explores two broad ethical themes that influenced the IDSA investigation. The first is the growing problem of conflicts of interest among guidelines developers, and the second is the increasing centralisation of medical decisions by insurance companies, which use treatment guidelines as a means of controlling the practices of individual doctors and denying treatment for patients. The implications of the first-ever antitrust investigation of medical guidelines and the proposed model to remediate the tainted IDSA guidelines process are also discussed.

Practices and challenges of infectious waste management: A qualitative descriptive study from tertiary care hospitals in Pakistan

PubMed Central

Kumar, Ramesh; Shaikh, Babar Tasneem; Somrongthong, Ratana; Chapman, Robert S

2015-01-01

Background and Objective: Infectious waste management practices among health care workers in the tertiary care hospitals have been questionable. The study intended to identify issues that impede a proper infectious waste management. Methods: Besides direct observation, in-depths interviews were conducted with the hospital administrators and senior management involved in healthcare waste management during March 2014. We looked at the processes related to segregation, collection, storage and disposal of hospital waste, and identified variety of issues in all the steps. Results: Serious gaps and deficiencies were observed related to segregation, collection, storage and disposal of the hospital wastes, hence proving to be hazardous to the patients as well as the visitors. Poor safety, insufficient budget, lack of trainings, weak monitoring and supervision, and poor coordination has eventually resulted in improper waste management in the tertiary hospitals of Rawalpindi. Conclusion: Study has concluded that the poor resources and lack of healthcare worker’s training in infectious waste results in poor waste management at hospitals. PMID:26430405

Construction and characterization of a full-length infectious molecular clone from the HIV type 1 subtype Thai-B isolated in Henan province, China.

PubMed

Wang, Zheng; Li, Jinyun; Li, Lin; Feng, Fuming; Li, Hanping; Bao, Zuoyi

2008-02-01

Among the various subtypes of the M group of human immunodeficiency virus type 1 (HIV-1), subtype Thai-B is the most prevalent in China, particularly in the country's central region. Here we report on the construction of an infectious molecular clone (CNHN24) of this HIV-1 subtype. We show that the viral stock obtained after transfection of CHNH24 could replicate efficiently in PBMC and MT4 cells. Unlike other previously reported HIV infectious clones, CNHN24 was constructed with the low copy plasmid pLG338, allowing for the HIV genome to be very stable during the process of molecular manipulation. Given the prevalence of subtype Thai-B in China's HIV epidemic, the availability of pCNHN24 as the first infectious molecular clone of this subtype provides a useful tool for a wide range of studies including antiviral drug and vaccine research as related to this subtype of viruses.

Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

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

Voss, Kelsey; Amaya, Moushimi; Mueller, Claudius

New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated inmore » Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses. - Highlights: • VEEV infection activated multiple components of the ERK signaling cascade. • Inhibition of ERK activation using Ag-126 inhibited VEEV multiplication. • Activation of ERK by Ceramide C6 increased infectious titers of TC-83. • Ag-126 inhibited virulent strains of all New World alphaviruses. • Ag-126 treatment increased percent survival of infected cells.« less

Comparison of Infectious Agents Susceptibility to Photocatalytic Effects of Nanosized Titanium and Zinc Oxides: A Practical Approach

NASA Astrophysics Data System (ADS)

Bogdan, Janusz; Zarzyńska, Joanna; Pławińska-Czarnak, Joanna

2015-08-01

Nanotechnology contributes towards a more effective eradication of pathogens that have emerged in hospitals, veterinary clinics, and food processing plants and that are resistant to traditional drugs or disinfectants. Since new methods of pathogens eradication must be invented and implemented, nanotechnology seems to have become the response to that acute need. A remarkable achievement in this field of science was the creation of self-disinfecting surfaces that base on advanced oxidation processes (AOPs). Thus, the phenomenon of photocatalysis was practically applied. Among the AOPs that have been most studied in respect of their ability to eradicate viruses, prions, bacteria, yeasts, and molds, there are the processes of TiO2/UV and ZnO/UV. Titanium dioxide (TiO2) and zinc oxide (ZnO) act as photocatalysts, after they have been powdered to nanoparticles. Ultraviolet (UV) radiation is an agent that determines their excitation. Methods using photocatalytic properties of nanosized TiO2 and ZnO prove to be highly efficient in inactivation of infectious agents. Therefore, they are being applied on a growing scale. AOP-based disinfection is regarded as a very promising tool that might help overcome problems in food hygiene and public health protection. The susceptibility of infectious agents to photocatalylic processes can be generally arranged in the following order: viruses > prions > Gram-negative bacteria > Gram-positive bacteria > yeasts > molds.

Airborne transmission of highly pathogenic influenza virus during processing of infected poultry

USDA-ARS?s Scientific Manuscript database

Human infections with H5N1 highly pathogenic avian influenza (HPAI) virus occur following exposure to virus-infected poultry, often during the slaughter processes. Infectious virus within bioaerosols was detected during laboratory-simulated processing of asymptomatic chickens infected with human- (c...

Quantitative membrane proteomics reveals a role for tetraspanin enriched microdomains during entry of human cytomegalovirus

PubMed Central

John, Nessy; Malouli, Daniel

2017-01-01

Human cytomegalovirus (HCMV) depends on and modulates multiple host cell membrane proteins during each stage of the viral life cycle. To gain a global view of the impact of HCMV-infection on membrane proteins, we analyzed HCMV-induced changes in the abundance of membrane proteins in fibroblasts using stable isotope labeling with amino acids (SILAC), membrane fractionation and protein identification by two-dimensional liquid chromatography and tandem mass spectrometry. This systematic approach revealed that CD81, CD44, CD98, caveolin-1 and catenin delta-1 were down-regulated during infection whereas GRP-78 was up-regulated. Since CD81 downregulation was also observed during infection with UV-inactivated virus we hypothesized that this tetraspanin is part of the viral entry process. Interestingly, additional members of the tetraspanin family, CD9 and CD151, were also downregulated during HCMV-entry. Since tetraspanin-enriched microdomains (TEM) cluster host cell membrane proteins including known CMV receptors such as integrins, we studied whether TEMs are required for viral entry. When TEMs were disrupted with the cholesterol chelator methyl-β-cylcodextrin, viral entry was inhibited and this inhibition correlated with reduced surface levels of CD81, CD9 and CD151, whereas integrin levels remained unchanged. Furthermore, simultaneous siRNA-mediated knockdown of multiple tetraspanins inhibited viral entry whereas individual knockdown had little effect suggesting essential, but redundant roles for individual tetraspanins during entry. Taken together, our data suggest that TEM act as platforms for receptors utilized by HCMV for entry into cells. PMID:29121670

Mediators and mechanisms of herpes simplex virus entry into ocular cells.

PubMed

Farooq, Asim V; Valyi-Nagy, Tibor; Shukla, Deepak

2010-06-01

The entry of herpes simplex virus into cells was once thought to be a general process. It is now understood that the virus is able to use multiple mechanisms for entry and spread, including the use of receptors and co-receptors that have been determined to be cell-type specific. This is certainly true for ocular cell types, which is important as the virus may use different mechanisms to gain access to multiple anatomic structures in close proximity, leading to various ocular diseases. There are some patterns that may be utilized by the virus in the eye and elsewhere, including surfing along filopodia in moving from cell to cell. There are common themes as well as intriguing differences in the entry mechanisms of herpes simplex virus into ocular cells. We discuss these issues in the context of conjunctivitis, keratitis, acute retinal necrosis, and other ocular diseases.

Mediators and Mechanisms of Herpes Simplex Virus Entry into Ocular Cells

PubMed Central

Farooq, Asim V.; Valyi-Nagy, Tibor; Shukla, Deepak

2010-01-01

The entry of herpes simplex virus (HSV) into cells was once thought to be a general process. It is now understood that the virus is able to use multiple mechanisms for entry and spread, including the use of receptors and co-receptors that have been determined to be cell-type specific. This is certainly true for ocular cell types, which is important as the virus may use different mechanisms to gain access to multiple anatomic structures in close proximity, leading to various ocular diseases. There are some patterns that may be utilized by the virus in the eye and elsewhere, including surfing along filopodia in moving from cell to cell. There are common themes as well as intriguing differences in the entry mechanisms of HSV into ocular cells. We discuss these issues in the context of conjunctivitis, keratitis, acute retinal necrosis and other ocular diseases. PMID:20465436

Multiscale Modeling of Virus Entry via Receptor-Mediated Endocytosis

NASA Astrophysics Data System (ADS)

Liu, Jin

2012-11-01

Virus infections are ubiquitous and remain major threats to human health worldwide. Viruses are intracellular parasites and must enter host cells to initiate infection. Receptor-mediated endocytosis is the most common entry pathway taken by viruses, the whole process is highly complex and dictated by various events, such as virus motions, membrane deformations, receptor diffusion and ligand-receptor reactions, occurring at multiple length and time scales. We develop a multiscale model for virus entry through receptor-mediated endocytosis. The binding of virus to cell surface is based on a mesoscale three dimensional stochastic adhesion model, the internalization (endocytosis) of virus and cellular membrane deformation is based on the discretization of Helfrich Hamiltonian in a curvilinear space using Monte Carlo method. The multiscale model is based on the combination of these two models. We will implement this model to study the herpes simplex virus entry into B78 cells and compare the model predictions with experimental measurements.

Apolipoprotein B-associated cholesterol is a determinant of treatment outcome in patients with chronic hepatitis C virus infection receiving anti-viral agents interferon-alpha and ribavirin.

PubMed

Sheridan, D A; Price, D A; Schmid, M L; Toms, G L; Donaldson, P; Neely, D; Bassendine, M F

2009-06-15

Hepatitis C virus (HCV) co-opts very-low-density lipoprotein (VLDL) pathways for replication, secretion and entry into hepatocytes and associates with apolipoprotein B (apoB) in plasma. Each VLDL contains apoB-100 and variable amounts of apolipoproteins E and C, cholesterol and triglycerides. To determine whether baseline lipid levels predicted treatment outcome. Retrospective analysis was performed of 250 chronic hepatitis C (CHC) patients who had received anti-viral agents interferon-alpha and ribavirin; 165 had a sustained virological response (SVR). Pre- and post-treatment nonfasting lipid profiles were measured and non-high-density lipoprotein (non-HDL) cholesterol (i.e. apoB-associated) was calculated. Binary logistic regression analysis assessed factors independently associated with treatment outcome. There was an independent association between higher apoB-associated cholesterol (non-HDL-C) and increased odds of SVR (odds ratio 2.09, P = 0.042). In multivariate analysis, non-HDL-C was significantly lower in HCV genotype 3 (g3) than genotype 1 (P = 0.007); this was reversible upon eradication of HCVg3 (pre-treatment non-HDL-C = 2.8 mmol/L, SVR = 3.6 mmol/L, P < 0.001). Higher apoB-associated cholesterol is positively associated with treatment outcome in CHC patients receiving anti-viral therapy, possibly due to competition between apoB-containing lipoproteins and infectious low-density HCV lipo-viral particles for hepatocyte entry via shared lipoprotein receptors.

Klebsiella Pneumoniae Liver Abscess: A Case Series of Six Asian Patients

PubMed Central

Oikonomou, Katerina G.; Aye, Myint

2017-01-01

Case series Patient: Female, 60 • Male, 45 • Male, 56 • Male, 65 • Female, 57 • Male, 35 Final Diagnosis: Klebsiella pneumoniae liver abscess Symptoms: Fever Medication: — Clinical Procedure: — Specialty: Infectious Diseases Objective: Rare co-existance of disease or pathology Background: Liver abscesses represent a serious infection of hepatic parenchyma and are associated with significant morbidity and mortality. The emergence of a new hypervirulent variant of Klebsiella pneumoniae, which can cause serious infections in the Asian population, is under investigation. We report a case series of six Asian patients hospitalized at our institution from January 2013 to November 2015 for liver abscess due to Klebsiella pneumoniae. Case Report: Charts of six Asian patients were retrospectively reviewed. Four patients were male and two were female. The mean age was 53 years (range: 35–64 years). All patients had no known past medical history of immunodeficiency. Three patients had multiple liver abscesses at the time of initial presentation. In five patients, the source of entry of the pathogenic microorganism was unknown and in one patient the suspected source of entry was the gastrointestinal tract. In three patients there was also concomitant Klebsiella pneumoniae bacteremia. The mean duration of antibiotic treatment was seven weeks and the mean duration of hospital stay was 13.5 days. Conclusions: Liver abscess should always be included in the differential diagnosis in cases of sepsis without obvious source and/or in the clinical scenarios of fever, abdominal pain, and liver lesions. PMID:28947732

Computer-based physician order entry: the state of the art.

PubMed Central

Sittig, D F; Stead, W W

1994-01-01

Direct computer-based physician order entry has been the subject of debate for over 20 years. Many sites have implemented systems successfully. Others have failed outright or flirted with disaster, incurring substantial delays, cost overruns, and threatened work actions. The rationale for physician order entry includes process improvement, support of cost-conscious decision making, clinical decision support, and optimization of physicians' time. Barriers to physician order entry result from the changes required in practice patterns, roles within the care team, teaching patterns, and institutional policies. Key ingredients for successful implementation include: the system must be fast and easy to use, the user interface must behave consistently in all situations, the institution must have broad and committed involvement and direction by clinicians prior to implementation, the top leadership of the organization must be committed to the project, and a group of problem solvers and users must meet regularly to work out procedural issues. This article reviews the peer-reviewed scientific literature to present the current state of the art of computer-based physician order entry. PMID:7719793