scholarly journals Characterization and Immunogenicity of Mycobacterium paratuberculosis Secreted and Cellular Proteins

1996 ◽  
Author(s):  
Herve Bercovier ◽  
Raul Barletta ◽  
Shlomo Sela
Keyword(s):  
Cellular Immunity ◽  
Diagnostic Tests ◽  
Stress Factors ◽  
Protein Antigen ◽  
Cellular Proteins ◽  
Secreted Proteins ◽  
Mycobacterium Paratuberculosis ◽  
The Usa ◽  
Acellular Vaccine

Our long-term goal is to develop an efficient acellular vaccine against paratuberculosis based on protein antigen(s). A prerequisite to achieve this goal is to analyze and characterize Mycobacterium paratuberculosis (Mpt) secreted and cellular proteins eliciting a protective immune response. In the context of this general objective, we proposed to identify, clone, produce, and characterize: the Mpt 85B antigen and other Mpt immunoreactive secreted proteins, the Mpt L7/L12 ribosomal protein and other immunoreactive cellular proteins, Mpt protein determinants involved in invasion of epithelial cells, and Mpt protein antigens specifically expressed in macrophages. Paratuberculosis is still a very serious problem in Israel and in the USA. In the USA, a recent survey evaluated that 21.6% of the dairy herd were infected with Mpt resulting in 200-250 million dollars in annual losses. Very little is known on the virulence factors and on protective antigens of Mpt. At present, the only means of controlling this disease are culling or vaccination. The current vaccines do not allow a clear differentiation between infected and vaccinated animals. Our long-term goal is to develop an efficient acellular paratuberculosis vaccine based on Mpt protein antigen(s) compatible with diagnostic tests. To achieve this goal it is necessary to analyze and characterize secreted and cellular proteins candidate for such a vaccine. Representative Mpt libraries (shuttle plasmid and phage) were constructed and used to study Mpt genes and gene products described below and will be made available to other research groups. In addition, two approaches were performed which did not yield the expected results. Mav or Mpt DNA genes that confer upon Msg or E. coli the ability to invade and/or survive within HEp-2 cells were not identified. Likewise, we were unable to characterize the 34-39 kDa induced secreted proteins induced by stress factors due to technical difficulties inherent to the complexity of the media needed to support substantial M. pt growth. We identified, isolated, sequenced five Mpt proteins and expressed four of them as recombinant proteins that allowed the study of their immunological properties in sensitized mice. The AphC protein, found to be up regulated by low iron environment, and the SOD protein are both involved in protecting mycobacteria against damage and killing by reactive oxygen (Sod) and nitrogen (AhpC) intermediates, the main bactericidal mechanisms of phagocytic cells. SOD and L7/L12 ribosomal proteins are structural proteins constitutively expressed. 85B and CFP20 are both secreted proteins. SOD, L7/L12, 85B and CFP20 were shown to induce a Th1 response in immunized mice whereas AphC was shown by others to have a similar activity. These proteins did not interfere with the DTH reaction of naturally infected cows. Cellular immunity provides protection in mycobacterial infections, therefore molecules inducing cellular immunity and preferentially a Th1 pathway will be the best candidate for the development of an acellular vaccine. The proteins characterized in this grant that induce a cell-mediated immunity and seem compatible with diagnostic tests, are good candidates for the construction of a future acellular vaccine.

Sanctions of the USA and the Policy of Bank of Russia:double Blow to the National Economy

2014 ◽  
pp. 13-29 ◽  
Author(s):  
S. Glazyev
Keyword(s):  
National Security ◽  
Economic Sanctions ◽  
Capital Flight ◽  
Practical Advice ◽  
The Us ◽  
Monetary Authorities ◽  
The Usa ◽  
Simultaneous Adoption ◽  
The Eu

This article examines fundamental questions of monetary policy in the context of challenges to the national security of Russia in connection with the imposition of economic sanctions by the US and the EU. It is proved that the policy of the Russian monetary authorities, particularly the Central Bank, artificially limiting the money supply in the domestic market and pandering to the export of capital, compounds the effects of economic sanctions and plunges the economy into depression. The article presents practical advice on the transition from external to domestic sources of long-term credit with the simultaneous adoption of measures to prevent capital flight.

Strategies to Protect Hematopoietic Stem Cells from Culture-Induced Stress Conditions

2020 ◽  
Vol 15 ◽  
Author(s):  
Fatima Aerts-Kaya
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Ex Vivo ◽  
Stress Conditions ◽  
Stress Factors ◽  
Hematopoietic Stem ◽  
Induced Stress

: In contrast to their almost unlimited potential for expansion in vivo and despite years of dedicated research and optimization of expansion protocols, the expansion of Hematopoietic Stem Cells (HSCs) in vitro remains remarkably limited. Increased understanding of the mechanisms that are involved in maintenance, expansion and differentiation of HSCs will enable the development of better protocols for expansion of HSCs. This will allow procurement of HSCs with long-term engraftment potential and a better understanding of the effects of the external influences in and on the hematopoietic niche that may affect HSC function. During collection and culture of HSCs, the cells are exposed to suboptimal conditions that may induce different levels of stress and ultimately affect their self-renewal, differentiation and long-term engraftment potential. Some of these stress factors include normoxia, oxidative stress, extra-physiologic oxygen shock/stress (EPHOSS), endoplasmic reticulum (ER) stress, replicative stress, and stress related to DNA damage. Coping with these stress factors may help reduce the negative effects of cell culture on HSC potential, provide a better understanding of the true impact of certain treatments in the absence of confounding stress factors. This may facilitate the development of better ex vivo expansion protocols of HSCs with long-term engraftment potential without induction of stem cell exhaustion by cellular senescence or loss of cell viability. This review summarizes some of available strategies that may be used to protect HSCs from culture-induced stress conditions.

scholarly journals Responses of Vertebrate Wildlife to Oil and Natural Gas Development: Patterns and Frontiers

2021 ◽  
Author(s):  
A. D. Chalfoun
Keyword(s):  
Natural Gas ◽  
Anthropogenic Activities ◽  
Spatial Scales ◽  
Habitat Type ◽  
Population Level ◽  
Low Frequencies ◽  
Natural Gas Development ◽  
The Usa ◽  
Oil And Natural Gas

Abstract Purpose of Review Anthropogenic activities can lead to the loss, fragmentation, and alteration of wildlife habitats. I reviewed the recent literature (2014–2019) focused on the responses of avian, mammalian, and herpetofaunal species to oil and natural gas development, a widespread and still-expanding land use worldwide. My primary goals were to identify any generalities in species’ responses to development and summarize remaining gaps in knowledge. To do so, I evaluated the directionality of a wide variety of responses in relation to taxon, location, development type, development metric, habitat type, and spatiotemporal aspects. Recent Findings Studies (n = 70) were restricted to the USA and Canada, and taxonomically biased towards birds and mammals. Longer studies, but not those incorporating multiple spatial scales, were more likely to detect significant responses. Negative responses of all types were present in relatively low frequencies across all taxa, locations, development types, and development metrics but were context-dependent. The directionality of responses by the same species often varied across studies or development metrics. Summary The state of knowledge about wildlife responses to oil and natural gas development has developed considerably, though many biases and gaps remain. Studies outside of North America and that focus on herpetofauna are lacking. Tests of mechanistic hypotheses for effects, long-term studies, assessment of response thresholds, and experimental designs that isolate the effects of different stimuli associated with development, remain critical. Moreover, tests of the efficacy of habitat mitigation efforts have been rare. Finally, investigations of the demographic effects of development across the full annual cycle were absent for non-game species and are critical for the estimation of population-level effects.

scholarly journals Person-Centered Health Care: An Approach That Integrates Acute and Long-Term Care

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 704-704
Author(s):  
Yuchi Young ◽  
Barbara Resnick
Keyword(s):  
Older Adults ◽  
Health Care ◽  
Health Systems ◽  
Long Term Care ◽  
The United States ◽  
World Population ◽  
Term Care ◽  
The Usa ◽  
Aged Society

Abstract The world population is aging. The proportion of the population over 60 will nearly double from 12% in 2015 to 22% in 2050. Global life expectancy has more than doubled from 31 years in 1900 to 72.6 years in 2019. The need for long-term care (LTC) services is expanding with the same rapidity. A comprehensive response is needed to address the needs of older adults. Learning from health systems in other countries enables health systems to incorporate best long-term care practices to fit each country and its culture. This symposium aims to compare long-term care policies and services in Taiwan, Singapore, and the USA where significant growth in aging populations is evidenced. In 2025, the aging population will be 20% in Taiwan, 20% in Singapore and 18 % in the USA. In the case of Taiwan, it has moved from aging society status to aged society, and to super-aged society in 27 years. Such accelerated rate of aging in Taiwan is unparalleled when compared to European countries and the United States. In response to this dramatic change, Taiwan has passed long-term care legislation that expands services to care for older adults, and developed person-centered health care that integrates acute and long-term care services. Some preliminary results related to access, care and patterns of utilization will be shared in the symposium. International Comparisons of Healthy Aging Interest Group Sponsored Symposium.

scholarly journals Assessment of thrombotic risk during long-term treatment of immune thrombocytopenia with fostamatinib

2021 ◽  
Vol 12 ◽  
pp. 204062072110108
Author(s):  
Nichola Cooper ◽  
Ivy Altomare ◽  
Mark R. Thomas ◽  
Phillip L. R. Nicolson ◽  
Steve P. Watson ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Term Treatment ◽  
Phase Iii ◽  
Thromboembolic Events ◽  
Thrombotic Risk ◽  
Long Term Treatment ◽  
Heavily Pretreated ◽  
The Usa ◽  
Syk Inhibitor

Background: Patients with immune thrombocytopenia (ITP) are at risk of bleeding and, paradoxically, thromboembolic events (TEEs), irrespective of thrombocytopenia. The risk of thrombosis is increased by advanced age, obesity, and prothrombotic comorbidities: cancer, hyperlipidemia, diabetes, hypertension, coronary artery disease, and chronic kidney disease, among others. Certain ITP treatments further increase the risk of TEE, especially splenectomy and thrombopoietin receptor agonists. Spleen tyrosine kinase (SYK) is a key signaling molecule common to thromboembolic and hemostatic (in addition to inflammatory) pathways. Fostamatinib is an orally administered SYK inhibitor approved in the USA and Europe for treatment of chronic ITP in adults. Methods: The phase III and extension studies included heavily pretreated patients with long-standing ITP, many of whom had risk factors for thrombosis prior to initiating fostamatinib. This report describes long-term safety and efficacy of fostamatinib in 146 patients with up to 5 years of treatment, a total of 229 patient-years, and assesses the incidence of thromboembolic events (by standardized MedDRA query). Results: Platelet counts ⩾50,000/µL were achieved in 54% of patients and the safety profile was as described in the phase III clinical studies with no new toxicities observed over the 5 years of follow-up. The only TEE occurred in one patient (0.7%, or 0.44/100 patient-years), who experienced a mild transient ischemic attack. This is a much lower rate than might be expected in ITP patients. Conclusion: This report demonstrates durable efficacy and a very low incidence of TEE in patients receiving long-term treatment of ITP with the SYK inhibitor fostamatinib. identifiers: NCT02076399, NCT02076412, and NCT02077192.

scholarly journals Tree Vitality and Forest Health: Can Tree-Ring Stable Isotopes Be Used as Indicators?

2021 ◽  
Author(s):  
Paolo Cherubini ◽  
Giovanna Battipaglia ◽  
John L. Innes
Keyword(s):  
Air Pollution ◽  
Stable Isotopes ◽  
Tree Ring ◽  
Forest Decline ◽  
Forest Health ◽  
Stress Factors ◽  
Tree Vitality ◽  
The Past ◽  
Physiological Processes

Abstract Purpose of Review Society is concerned about the long-term condition of the forests. Although a clear definition of forest health is still missing, to evaluate forest health, monitoring efforts in the past 40 years have concentrated on the assessment of tree vitality, trying to estimate tree photosynthesis rates and productivity. Used in monitoring forest decline in Central Europe since the 1980s, crown foliage transparency has been commonly believed to be the best indicator of tree condition in relation to air pollution, although annual variations appear more closely related to water stress. Although crown transparency is not a good indicator of tree photosynthesis rates, defoliation is still one of the most used indicators of tree vitality. Tree rings have been often used as indicators of past productivity. However, long-term tree growth trends are difficult to interpret because of sampling bias, and ring width patterns do not provide any information about tree physiological processes. Recent Findings In the past two decades, tree-ring stable isotopes have been used not only to reconstruct the impact of past climatic events, such as drought, but also in the study of forest decline induced by air pollution episodes, and other natural disturbances and environmental stress, such as pest outbreaks and wildfires. They have proven to be useful tools for understanding physiological processes and tree response to such stress factors. Summary Tree-ring stable isotopes integrate crown transpiration rates and photosynthesis rates and may enhance our understanding of tree vitality. They are promising indicators of tree vitality. We call for the use of tree-ring stable isotopes in future monitoring programmes.

scholarly journals Analytical detection of influenza A(H3N2)v and other A variant viruses from the USA by rapid influenza diagnostic tests

2012 ◽  
Vol 7 (4) ◽  
pp. 491-496 ◽  
Author(s):  
Amanda Balish ◽  
Rebecca Garten ◽  
Alexander Klimov ◽  
Julie Villanueva
Keyword(s):  
Diagnostic Tests ◽  
Influenza A ◽  
The Usa ◽  
Analytical Detection

Glycyrrhizic acid: the assessment of a no effect level

2000 ◽  
Vol 19 (8) ◽  
pp. 434-439 ◽  
Author(s):  
C E M van Gelderen ◽  
J A Bijlsma ◽  
W van Dokkum ◽  
T J F Savelkoull
Keyword(s):  
Body Weight ◽  
Pilot Study ◽  
Glycyrrhizic Acid ◽  
Mild Hypertension ◽  
Daily Intake ◽  
Long Term Effects ◽  
Healthy Female ◽  
The Usa ◽  
Effect Level

Because from earlier experiments in rats and a pilot study in humans a no effect level of glycyrrhizic acid could not be established, a second experiment was performed in healthy volunteers. The experiment was performed in females only, because the effects were most marked in females in the pilot study. Doses of 0, 1, 2 and 4 mg glycyrrhizic acid/kg body weight were administered orally for 8 weeks to 39 healthy female volunteers aged 19-40 years. The experimentlasted 12 weeks including an adaptation and a “wash-out” period.Ano-effectlevel of2 mg/kgis proposed from the results ofthis study, from which an acceptable daily intake (ADI) of 0.2 mg/kg body weight can be extrapolated with a safety factor of 10. This means consumption of 12 mg glycyrrhizic acid/day for a person with a body weight of 60 kg. This would be equal to 6 g licorice a day, assuming that licorice contains 0.2% of glycyrrhizic acid. The proposed ADI is below the limit advised by the Dutch Nutrition Council of 200 mg glycyrrhizic acid/day. This reflects the relatively mild acute toxicity of glycyrrhizic acid, which is also emphasised by the “generally recognised as safe” (GRAS) status of glycyrrhizic acid in the USA in 1983. However, the long-term effects of a mild chronic intoxication (causing, for example, a mild hypertension), although not immediately lethal, justify special attention to the amount of glycyrrhizic acid used daily.

An International Appraisal of the Minimum Duration of Chronic Animal Toxicity Studies

1992 ◽  
Vol 11 (3) ◽  
pp. 155-162 ◽  
Author(s):  
Cynthia E. Lumley ◽  
Christopher Parkinson ◽  
Stuart R. Walker
Keyword(s):  
Data Base ◽  
Toxicity Tests ◽  
Repeat Dose ◽  
Carcinogenic Potential ◽  
New Findings ◽  
Regulatory Guidelines ◽  
The Usa ◽  
Adequate Data ◽  
Pathology Data

1 There are international differences in regulatory guidelines for the appropriate duration of chronic, two species repeat-dose animal tests for new medicines intended for long-term use in man, ranging from 6 months in Europe to 12 months in Japan and the USA.1 2 An adequate data base is necessary to support any challenge to the scientific rationale behind regulatory guidelines with regard to the design, duration and relevance of toxicity tests of new medicines. 3 The Centre for Medicines Research has established an international toxicology data base which has been expanded to enable a comparison of data obtained within 6 months, with information from longer periods, for 154 studies. 4 Although new findings were revealed after 6 months for 9/75 cases for which pathology data are available at 6 and 12 months or longer, and 21/80 with data at 1 or 3 (but not 6 months) and 12 months or longer, in no instance did these influence the decision to drop or further develop the compounds in question. 5 These data suggest that a 6-month period of dosing is all that is routinely required for evaluating the chronic toxic (excluding carcinogenic) potential of a new chemical entity intended for therapeutic use.

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