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At least 37 records · Page 2

Sequence Length of HIV-1 Subtype B Increases over Time: Analysis of a Cohort of Patients with Hemophilia over 30 Years

We aimed to investigate whether the sequence length of HIV-1 increases over time. We performed a longitudinal analysis of full-length coding region sequences (FLs) during an HIV-1 outbreak among patients with hemophilia and local controls infected with the Korean subclade B of HIV-1 (KSB). Genes were amplified by overlapping RT-PCR or nested PCR and subjected to direct sequencing. Overall, 141 FLs were sequentially determined over 30 years in 62 KSB-infected patients. Phylogenetic analysis indicated that within KSB, two FLs from plasma donors O and P comprised two clusters, together with 8 and 12 patients with hemophilia, respectively. Signature pattern analysis of the KSB of HIV-1 revealed 91 signature nucleotide residues (1.1%). In total, 48 and 43 signature nucleotides originated from clusters O and P, respectively. Six positions contained 100% specific nucleotide(s) in clusters O and P. In-depth FL analysis for over 30 years indicated that the KSB FL significantly increased over time before combination antiretroviral therapy (cART) and decreased with cART. This increase occurred due to the significant increase in env and nef genes, originating in the variable regions of both genes. The increase in sequence length of HIV-1 over time suggests an evolutionary direction.

59 BASIC BIOLOGICAL SCIENCES↗

High Sensitivity of Mobile Phone Microscopy Screening for Schistosoma haematobium in Azaguié, Côte d’Ivoire

Schistosomiasis infections continue to impact African settings disproportionately, and there is an urgent need for novel tools to evaluate infection control and elimination strategies at the community level. Mobile phone microscopes are portable and semiautomated devices with multiple applications for screening neglected tropical diseases. In a community-based schistosomiasis screening program in Azaguié, Côte d’Ivoire, mobile phone microscopy demonstrated a sensitivity of 85.7% (95% CI: 69.7–95.2%) and specificity of 93.3% (95% CI: 87.7–96.9%) for Schistosoma haematobium identification compared with conventional light microscopy, and 95% sensitivity (95% CI: 74.1–99.8%) with egg concentrations of five or more per 10 mL of urine. Mobile phone microscopy is a promising tool for schistosomiasis control and elimination efforts.

59 BASIC BIOLOGICAL SCIENCES↗

Proceedings from the 2001 NASA Occupational Health Conference: Risk Assessment and Management in 2001

This Conference convened approximately 86 registered participants of invited guest speakers, NASA presenters, and a broad spectrum of the Occupational Health disciplines representing NASA Headquarters and all NASA Field Centers. Two days' Professional Development Courses on Exposure Assessment Strategies and Statistics and on Advanced Cardiac Life Support training and recertification preceded the Conference. With the theme, 'Risk Assessment and Management in 2001,' conferees were first provided updates from the Program Principal Center Office and the Headquarters Office. Plenary sessions elaborated on several topics: biological terrorism, OSHA recordability, Workers' Compensation issues, Federal ergonomic standards, bridging aerospace medicine and occupational health-especially in management of risk in spaceflight, and EAP operations with mission failures. A keynote address dealt with resiliency skills for 21st century workers and two NASA astronaut speakers highlighted a tour of the Johnson Space Center. During discipline specific breakout sessions, current issues in occupational health management and policy, credentialing and privileging, health risk assessment, measurement and standardization, audits, database development, prevention and rehabilitation, international travel and infection control, employee assistance, nursing process, and environmental health were presented.

Roberson, Sheri↗

Physician's Breakout Session

Dr. William Barry, Manager, NASA Occupational Health Program, moderated this session. As in one of the opening sessions, he re-iterated that the overall theme for the next year will be facilitating and implementing NIAT-1 (NASA Integrated Action Team - Action 1). He presented a candidate list of topics for consideration and discussion: (1) NIAT-1; (2) Skin cancer detection and the NASA Solar Safe Program; (3) Weapons of mass destruction; (4) Quality assurance; (5) Audits; (6) Environment of care; (7) Infection control; (8) Medication management; and (9) Confidentiality of medical records.

Barry, William↗

NRSF causes cAMP-sensitive suppression of sodium current in cultured hippocampal neurons

The neuron restrictive silencer factor (NRSF/REST) has been shown to bind to the promoters of many neuron-specific genes and is able to suppress transcription of Na(+) channels in PC12 cells, although its functional effect in terminally differentiated neurons is unknown. We constructed lentiviral vectors to express NRSF as a bicistronic message with green fluorescent protein (GFP) and followed infected hippocampal neurons in culture over a period of 1-2 wk. NRSF-expressing neurons showed a time-dependent suppression of Na(+) channel function as measured by whole cell electrophysiology. Suppression was reversed or prevented by the addition of membrane-permeable cAMP analogues and enhanced by cAMP antagonists but not affected by increasing protein expression with a viral enhancer. Secondary effects, including altered sensitivity to glutamate and GABA and reduced outward K(+) currents, were duplicated by culturing GFP-infected control neurons in TTX. The striking similarity of the phenotypes makes NRSF potentially useful as a genetic "silencer" and also suggests avenues of further exploration that may elucidate the transcription factor's in vivo role in neuronal plasticity.

Hippocampus/cytology/metabolism↗

Application of Emerging Pharmaceutical Technologies for Therapeutic Challenges of Space Exploration Missions

An important requirement of therapeutics for extended duration exploration missions beyond low Earth orbit will be the development of pharmaceutical technologies suitable for sustained and preventive health care in remote and adverse environmental conditions. Availability of sustained, stable and targeted delivery pharmaceuticals for preventive health of major organ systems including gastrointestinal, hepato-renal, musculo-skeletal and immune function are essential to offset adverse effects of space environment beyond low Earth orbit. Specifically, medical needs may include multi-drug combinations for hormone replacement, radiation protection, immune enhancement and organ function restoration. Additionally, extended stability of pharmaceuticals dispensed in space must be also considered in future drug development. Emerging technologies that can deliver stable and multi-therapy pharmaceutical preparations and delivery systems include nanotechnology based drug delivery platforms, targeted-delivery systems in non-oral and non-parenteral formulation matrices. Synthetic nanomaterials designed with molecular precision offer defined structures, electronics, and chemistries to be efficient drug carriers with clear advantages over conventional materials of drug delivery matricies. Nano-carrier materials like the bottle brush polymers may be suitable for systemic delivery of drug cocktails while Superparamagnetic Iron Oxide Nanoparticles or (SPIONS) have great potential to serve as carriers for targeted drug delivery to a specific site. These and other emerging concepts of drug delivery and extended shelf-life technologies will be reviewed in light of their application to address health-care challenges of exploration missions. Innovations in alternate treatments for sustained immune enhancement and infection control will be also discussed.

Putcha, Lakshmi↗

Effect of treatment with interferon-gamma and concanavalin A on the course of infection of mice with Salmonella typhimurium strain LT-2

The effect of pretreatment of mice with 34 units/day, for five days, of interferon-gamma (IFN-gamma) on the course of infection with LD50 of Salmonella typhimurium strain LT-2 was assessed, using two IFN preparations: (1) a hybridoma supernatant fluid containing concanavalin-A-induced IFN-gamma activity and (2) pure murine IFN-gamma produced by recombinant DNA technology. The hybridoma supernatant-treated Salmonella-infected mice were found to die faster than mice treated only with Salmonella. Pure murine IFN-gamma was found to protect infected mice significantly, with 95 percent of mice surviving LD50 infection. In contrast, the Salmonella-infected mice treated with hybridoma supernatant were found to die faster than the Salmonella-infected untreated controls. Mice treated with concanavalin A alone prior to infection with S. typhimurium died more quickly than the untreated infected controls, suggesting that contamination with concanavalin A had a detrimental effect on mice survival.

Gould, Cheryl L.↗

Transcription Factors Controlling the Rhizobium–Legume Symbiosis: Integrating Infection, Organogenesis and the Abiotic Environment

Abstract Legume roots engage in a symbiotic relationship with rhizobia, leading to the development of nitrogen-fixing nodules. Nodule development is a sophisticated process and is under the tight regulation of the plant. The symbiosis initiates with a signal exchange between the two partners, followed by the development of a new organ colonized by rhizobia. Over two decades of study have shed light on the transcriptional regulation of rhizobium–legume symbiosis. A large number of transcription factors (TFs) have been implicated in one or more stages of this symbiosis. Legumes must monitor nodule development amidst a dynamic physical environment. Some environmental factors are conducive to nodulation, whereas others are stressful. The modulation of rhizobium–legume symbiosis by the abiotic environment adds another layer of complexity and is also transcriptionally regulated. Several symbiotic TFs act as integrators between symbiosis and the response to the abiotic environment. In this review, we trace the role of various TFs involved in rhizobium–legume symbiosis along its developmental route and highlight the ones that also act as communicators between this symbiosis and the response to the abiotic environment. Finally, we discuss contemporary approaches to study TF-target interactions in plants and probe their potential utility in the field of rhizobium–legume symbiosis.

Cell Biology↗

Experimental system for the control of surgically induced infections, operating and maintenance instructions D203613-004

An experimental portable system used to control surgically induced infections is described. The system consists of a portable clean room comprised of a laminar flow filter system consistent with Federal standards; a helmet-shoulder pad assembly; a communication system; a helmet ventilation system; a transparent walled enclosure; and surgical gowns. Guidelines for the set up and operation of such equipment are given along with corrective steps to use in case of system malfunctions. Cleaning procedures, maintenance requirements, and disassembly and transfer particulars are included.

Tevebaugh, M. D.↗

Experimental system for the control of surgically induced infections

The results are presented of the development tests performed on the experimental system for the control of surgically induced infections. Tests were performed on the portable clean room to demonstrate assembly, collapsability, portability and storage. Collapsing, relocating and storing within the surgery room can be accomplished in 12 minutes. The storage envelope dimensions are 1.64 m x 4.24 m x 2.62 m high. The disassembly transfer to another room, and reassembly were demonstrated. The laminar air flow velocity profile within the enclosure was measured. In the undisturbed area of the enclosure the air flow met the Federal Standard 209a requirements of 27.45 meters per minute + or - 6.10 meters per minute. Smoke tests with simulated surgery equipment and personnel in the enclosure did not indicate any detrimental air flow patterns. It is concluded that the system as designed will perform the functions required for its intended use.

Source record↗

Experimental system, and its evaluation for the control of surgically inducted infections

The effect is reported to design, fabricate, test and evaluate a prototype experimental system for the control of surgically induced infections. The purpose is to provide the cleanest possible environment within a hospital surgery room and eliminate contamination sources that could cause infections during surgery. The system design is described. The system provides for a portable laminar flow clean room, a full bubble helmet system with associated communications and ventilation subsystems for operating room personnel, and surgical gowns that minimize the migration of bacteria. The development test results consisting of portability, laminar flowrate, air flow pattern, electrostatic buildup, noise level, ventilation, human factors, electrical and material compatibility tests are summarized. The conclusions are that the experimental system is effective in reducing the airborne and wound contamination although the helmets and gowns may not be a significant part of this reduction. Definitive conclusions with regard to the infection rate cannot be made at this time.

Tevebaugh, M. D.↗

Within-Host Phenotypic Evolution and the Population-Level Control of Chronic Viral Infections by Treatment and Prophylaxis

Chronic viral infections can persist for decades spanning thousands of viral generations, leading to a highly diverse population of viruses with its own complex evolutionary history. We propose an expandable mathematical framework for understanding how the emergence of genetic and phenotypic diversity affects the population-level control of those infections by both non-curative treatment and chemo-prophylactic measures. Our frameworks allows both neutral and phenotypic evolution, and we consider the specific evolution of contagiousness, resistance to therapy, and efficacy of prophylaxis. We compute both the controlled and uncontrolled, population-level basic reproduction number accounting for the within-host evolutionary process where new phenotypes emerge and are lost in infected persons, which we also extend to include both treatment and prophylactic control efforts. We used these results to discuss the conditions under which the relative efficacy of prophylactic versus therapeutic methods of control are superior. Finally, we give expressions for the endemic equilibrium of these models for certain constrained versions of the within-host evolutionary model providing a potential method for estimating within-host evolutionary parameters from population-level genetic sequence data.

sensitivity analysis↗

Protection of wheat against leaf and stem rust and powdery mildew diseases by inhibition of polyamine metabolism

In higher plants, polyamines arise from arginine by one of two pathways: via ornithine and ornithine decarboxylase or via agmatine and arginine decarboxylase but in fungi, only the ornithine decarboxylase pathway is present. Since polyamines are required for normal growth of microorganisms and plants and since the ornithine pathway can be irreversibly blocked by alpha-difluoromethylornithine (DFMO) which has no effect on arginine decarboxylase, fungal infection of green plants might be controlled by the site-directed use of such a specific metabolic inhibitor. DFMO at relatively low concentrations provided effective control of the three biotrophic fungal pathogens studied, Puccinia recondita (leaf rust), P. graminis f. sp. tritici (stem rust), and Erysiphe graminis (powdery mildew) on wheat (Triticum aestivum L.) Effective control of infection by leaf or stem rust fungi was obtained with sprays of DFMO that ranged from about 0.01 to 0.20 mM in experiments where the inhibitor was applied after spore inoculation. The powdery mildew fungus was somewhat more tolerant of DFMO, but good control of the pathogen was obtained at less than 1.0 mM. In general, application of DFMO after spore inoculation was more effective than application before inoculation. Less control was obtained following treatment with alpha-difluoromethylarginine (DFMA) but the relatively high degree of control obtained raises the possibility of a DFMA to DFMO conversion by arginase.

NASA Discipline Number 40-10↗

Viral infections likely mediate microbial controls on ecosystem responses to global warming

Abstract Climate change is affecting how energy and matter flow through ecosystems, thereby altering global carbon and nutrient cycles. Microorganisms play a fundamental role in carbon and nutrient cycling and are thus an integral link between ecosystems and climate. Here, we highlight a major black box hindering our ability to anticipate ecosystem climate responses: viral infections within complex microbial food webs. We show how understanding and predicting ecosystem responses to warming could be challenging—if not impossible—without accounting for the direct and indirect effects of viral infections on different microbes (bacteria, archaea, fungi, protists) that together perform diverse ecosystem functions. Importantly, understanding how rising temperatures associated with climate change influence viruses and virus-host dynamics is crucial to this task, yet is severely understudied. In this perspective, we (i) synthesize existing knowledge about virus-microbe-temperature interactions and (ii) identify important gaps to guide future investigations regarding how climate change might alter microbial food web effects on ecosystem functioning. To provide real-world context, we consider how these processes may operate in peatlands—globally significant carbon sinks that are threatened by climate change. We stress that understanding how warming affects biogeochemical cycles in any ecosystem hinges on disentangling complex interactions and temperature responses within microbial food webs.

54 ENVIRONMENTAL SCIENCES↗

Controlling Host Responses to Infection

Pathogen invasion of host cells causes a myriad of functional changes including alterations of chromatin accessibility often limiting defense responses, shunting of cellular resources to centers of viral replication, and rearrangement of intracellular membranes to facilitate genome reproduction and progeny release. Systems biology approaches provide global snapshots of pathogen induced changes following infection and provide a variety of tools to begin to define how cellular homeostasis is disrupted, but improvements on these tools are required to determine how cellular functions are altered post infection. Chromatin accessibility techniques, biochemical assays to assess the activity of epigenetic enzymes, scalable sample collection platforms, and activity-based probes were used to characterize how human respiratory viruses modify host responses in infected human lungs over time. These studies enhanced our knowledge of how pathogens usurp the host environment during infection and identify additional targets for future evaluations of medical countermeasures.

59 BASIC BIOLOGICAL SCIENCES↗

Experimental system for the control of surgically induced infections

The development tests to be performed on the experimental system are described in detail. The test equipment, conditions, and procedures are given. The portable clean room tests include assembly, collapsability, portability, and storage; laminar flow rate; static pressure; air flow pattern; and electrostatic buildup. The other tests are on the ventilation system, human factors evaluation, electrical subsystem, and material compatibility.

Tevebaugh, M. D.↗

Experimental system for the control of surgically induced infections

The experimental system is described, and the procedures for surgery usage and maintenance are outlined. Basically the system consists of the following: (1) a portable clean room comprised of a horizontal laminar flow filter system and a transparent walled enclosure, (2) a helmet-shoulder pad assembly, (3) a communications system, (4) a helmet ventilation system, and (5) surgical gowns.

Source record↗