Search NASA⌕ Search

SEARCH · Search NASA

Results for “lung (human)”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11

Cross-protective antibodies against common endemic respiratory viruses

Respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and human parainfluenza virus types one (HPIV1) and three (HPIV3) can cause severe disease and death in immunocompromised patients, the elderly, and those with underlying lung disease. A protective monoclonal antibody exists for RSV, but clinical use is limited to high-risk infant populations. Hence, therapeutic options for these viruses in vulnerable patient populations are currently limited. Here, we present the discovery, in vitro characterization, and in vivo efficacy testing of two cross-neutralizing monoclonal antibodies, one targeting both HPIV3 and HPIV1 and the other targeting both RSV and HMPV. The 3 × 1 antibody is capable of targeting multiple parainfluenza viruses; the MxR antibody shares features with other previously reported monoclonal antibodies that are capable of neutralizing both RSV and HMPV. We obtained structures using cryo-electron microscopy of these antibodies in complex with their antigens at 3.62 Å resolution for 3 × 1 bound to HPIV3 and at 2.24 Å for MxR bound to RSV, providing a structural basis for in vitro binding and neutralization. Together, a cocktail of 3 × 1 and MxR could have clinical utility in providing broad protection against four of the respiratory viruses that cause significant morbidity and mortality in at-risk individuals.

60 APPLIED LIFE SCIENCES↗

Toxicologic evaluation of the migration of a plasticizer, DI (2-ethylhexyl) phthalate (DEHP) from vinyl plastics

The intravenous administration of DEHP solubilized by means of a number of different detergents leads to respiratory distress and death in rats. At autopsy the lungs are grossly enlarged, edamatous, and hemorrhagic. Light and electron microscopic evaluation of the lungs indicate engorgement of the interalveolar septa with edema fluid and polymorphonuclear leucocytes, degranulation of the leukocytes, and progessive destruction of the endothelial and epithelial cells. Consistent with the conclusion that solubilized DEHP results in a syndrome of "shock lung" is the associated massive fall in arterial blood pressure and the prevention of the lung pathology by pretreatment with pharmacologic doses of an antiinflammatory steroid, methylprednisolone. Evidence is also presented that suggests that the DEHP inadvertently administered to humans during transfusions is also in a solubilized state in the plasma.

Rubin, R. J.↗

Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates

The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of vaccines has provided highly anticipated relief, but effective therapeutics are required to further reduce the risk and severity of infections. Monoclonal antibodies have been shown to be effective as therapeutics for SARS-CoV-2, but as new variants of concern (VoC) continue to emerge, their utility and use have waned due to limited or no efficacy against these variants. Furthermore, cumbersome systemic administration limits easy and broad access to such drugs. As well, concentrations of systemically administered antibodies in the mucosal epithelium, a primary site of initial infection, are dependent on neonatal Fc receptor mediated transport and require high drug concentrations. To reduce the viral load more effectively in the lung, we developed an inhalable formulation of a SARS-CoV-2 neutralizing antibody binding to a conserved epitope on the Spike protein, ensuring pan-neutralizing properties. Administration of this antibody via a vibrating mesh nebulization device retained antibody integrity and resulted in effective distribution of the antibody in the upper and lower respiratory tract of non-human primates (NHP). In comparison with intravenous administration, significantly higher antibody concentrations can be obtained in the lung, resulting in highly effective reduction in viral load post SARS-CoV-2 challenge. This approach may reduce the barriers of access and uptake of antibody therapeutics in real-world clinical settings and provide a more effective blueprint for targeting existing and potentially emerging respiratory tract viruses.

60 APPLIED LIFE SCIENCES↗

The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection

SARS-CoV-2 infection-induced aggravation of host innate immune response not only causes tissue damage and multiorgan failure in COVID-19 patients but also induces host genome damage and activates DNA damage response pathways. To test whether the compromised DNA repair capacity of individuals modulates the severity of COVID-19 infection, we analyze DNA repair gene expression in publicly available patient datasets and observe a lower level of the DNA glycosylase NEIL2 in the lungs of severely infected COVID-19 patients. This observation of lower NEIL2 levels is further validated in infected patients, hamsters and ACE2 receptor-expressing human A549 (A549-ACE2) cells. Furthermore, delivery of recombinant NEIL2 in A549-ACE2 cells shows decreased expression of proinflammatory genes and viral E-gene, as well as lowers the yield of viral progeny compared to mock-treated cells. Mechanistically, NEIL2 cooperatively binds to the 5’-UTR of SARS-CoV-2 genomic RNA to block viral protein synthesis. Collectively, these data strongly suggest that the maintenance of basal NEIL2 levels is critical for the protective response of hosts to viral infection and disease.

60 APPLIED LIFE SCIENCES↗

Omics-Lethal Human Viruses, Influenza A Experiment IM103

The purpose of this experiment was to evaluate the host response to wild-type Influenza A/Vietnam/1203/2004 (H5N1; "VN1203") virus infection and mock infection. Sample data was obtained for mouse lung tissue and processed for mRNA, miRNA, proteomics, lipidomics, and metabolomics expression analysis. Secondary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics, metabolomics, lipidomics, and transcriptomics dataset download each have a direct relationship to a primary sample submission corresponding to a specific Influenza A virus infection.

59 BASIC BIOLOGICAL SCIENCES↗

The Next Generation of Cold Immersion Dry Suit Design Evolution for Hypothermia Prevention

This new utility patent is an active design that relies on the lung's role as an organic heat exchanger for providing deep body core heating of air. It is based on the fact that the greatest heat loss mechanism for an insulated human body immersed in a cold water environment is due to heat loss through respiration. This innovation successfully merges two existing technologies (cold immersion suit and existing valve technologies) to produce a new product that helps prevent against the onset of hypothermia at sea. During normal operations, a human maintains an approximate body temperature of [98.6 F (37 C)]. A mechanism was developed to recover the warm temperature from the body and reticulate it in a survival suit. The primary intention is to develop an encompassing systems design that can both easily and cost effectively be integrated in all existing currently manufactured cold water survival suits, and as such, it should be noted that the cold water immersion suit is only used as a framework or tool for laying out the required design elements. At the heart of the suit is the Warm Air Recovery (WAR) system, which relies on a single, large Main Purge Valve (MPV) and secondary Purge Valves (PV) to operate. The main purge valve has a thin membrane, which is normally closed, and acts as a one-way check valve. When warm air is expelled from the lungs, it causes the main purge valve to open. Air forced from the MPV is dumped directly into the suit, thereby providing warmth to the torso, legs, and arms. A slight positive over-pressure in the suit causes warm waste air (or water if the suit is punctured) to be safely vented into the sea through large PVs located at the bottom of each arm and leg. The secondary purge valves act to prevent the buildup of large concentrations of CO2 gas and help guard against asphyxia. It is noted that the MPV causes the inhalation and exhalation cycles to be completely isolated from one another in the current suit design.

Galofaro, Joel↗

Toxicological Risks During Human Space Exploration

The goal of toxicological risk assessment of human space flight is to identify and quantify significant risks to astronaut health from air pollution inside the vehicle or habitat, and to develop a strategy for control of those risks. The approach to completing a toxicological risk assessment involves data and experience on the frequency and severity of toxicological incidents that have occurred during space flight. Control of these incidents depends on being able to understand their cause from in-flight and ground-based analysis of air samples, crew reports of air quality, and known failures in containment of toxic chemicals. Toxicological risk assessment in exploration missions must be based on an evaluation of the unique toxic hazards presented by the habitat location. For example, lunar and Martian dust must be toxicologically evaluated to determine the appropriate control measures for exploration missions. Experience with near-earth flights has shown that the toxic products from fires present the highest risk to crew health from air pollution. Systems and payload leaks also present a significant hazard. The health risk from toxicity associated with materials offgassing or accumulation of human metabolites is generally well controlled. Early tests of lunar and Martian dust simulants have shown that each posses the potential to cause fibrosis in the lung in a murine model. Toxicological risks from air pollutants in space habitats originate from many sources. A number of risks have been identified through near-earth operations; however, the evaluation of additional new risks present during exploration missions will be a challenge.

James, John T.↗

No Need to Wait for the Clean Air Dividend

Controlling smog and soot is the classic win-win situation, so it's great that the world is finally waking up to the idea. WHAT if there was a way to simultaneously slow down climate change, save millions of lives, improve crop yields and contribute to sustainable development and energy security? It sounds too good to be true, but it is possible. It won't be free or easy, but with some effort and moderate investment, it can be done. The way to do it is to reduce emissions leading to two types of pollution: black carbon and ozone. These are the only pollutants that we know contribute to both global warming and poor air quality. Black carbon is essentially soot, emitted from incomplete combustion of fossil fuels and biomass. It warms the climate in two ways: by absorbing heat in the atmosphere - similar to the greenhouse effect - and by reducing Earth's albedo, or ability to reflect sunlight. Inhaled into the lungs, it leads to cancer and cardiovascular disease. Ozone in the atmosphere also acts as a greenhouse gas, while ground-level ozone is toxic to humans and plants, so leads to both premature death and reduced crop yields. Ozone is not emitted directly but is produced by the action of sunlight on other pollutants, which are known as ozone precursors. Since black carbon and ozone are important components of soot and smog, a great deal of effort has already been put into developing methods to reduce emissions. So effective technology is available, but needs wider implementation. The recommended control measures for black carbon include widespread and tight emission standards on diesel cars and trucks; improved solid fuel cooking stoves, brick kilns and coke ovens in the developing world; and a ban on the open burning of agricultural waste. Implementation of these measures would have a rapid impact on the climate and human health, and also have the added benefit of greatly reducing emissions of carbon monoxide, an important ozone precursor. A second key ozone precursor is methane, which is also a powerful greenhouse gas in its own right. Control measures include reducing leaks from natural gas pipelines and storage tanks, and capturing it from coal, gas and oil extraction, landfills and wastewater treatment plants. Aeration of rice paddies and manure management can also reduce methane releases. Captured methane can often be sold or turned into power. In Monterrey, Mexico, for example, electricity generated from methane collected from the city landfill powers the public transportation system. So such measures can be beneficial even when ignoring the health and climate effects, as they can contribute to energy security and often pay for themselves. According to calculations by me and my colleagues, phasing in all these measures over the next 20 years would reduce global warming by about 0.5 degC in 2050, half of the projected increase between now and then (Science, vol 335, p 183). Regional benefits would be even greater, as black carbon disrupts rainfall patterns and magnifies warming and melting of snow and ice in parts of the world including the Arctic and the Himalayas. On top of the climate benefits, cutting black carbon and ozone would prevent over 3 million premature deaths from air pollution, and increase yields of staple crops by roughly 50 million tonnes a year. Improved cooking stoves would also decrease the demand for firewood in the developing world, reducing deforestation and freeing up time for those who collect wood - primarily women and children - to pursue other activities such as education. Similarly, improved brick kilns now being used in parts of Latin America and Asia require half as much fuel as traditional ones and are less time-intensive for the operators. This means that in addition to their environmental benefits, these measures can contribute to sustainable and human development. Tackling black carbon and methane is clearly a great idea, so why hasn't it been done already? There are many barriers. The upfront costs of some measures can be prohibitive even when they eventually pay for themselves. But this can be overcome by mechanisms such as international financing of capital costs. For other measures, the costs are typically borne by a few while the benefits accrue to everybody. In such cases civil society and governments must get involved. Governments are starting to act. In February, the US, Canada, Sweden, Bangladesh, Ghana and Mexico launched the Climate and Clean Air Coalition to support implementation of measures like these. This coalition will hopefully expand and achieve rapid, widespread adoption of measures to cut black carbon and ozone. While the climate benefits will be substantial, it is important to note that these measures cannot substitute for cuts in carbon dioxide. Black carbon, ozone, carbon monoxide and methane stay in the atmosphere for a fairly short time - a few days for black carbon and about a decade for methane. They thus respond quickly to emissions changes and give us substantial leverage over near-term climate change. In contrast, carbon dioxide is very long-lived and so responds slowly to emissions changes. This means that cuts have little immediate impact, but it also means they must be made now to avoid disastrous changes later on. Controlling short-lived climate pollutants is thus an issue of fairness. Much as failure to reduce carbon dioxide emissions soon would condemn future generations to disastrous change, failure to reduce near-term climate change condemns those alive today to suffer worsening effects of the sort already seen. Some wonder if we really can do both. We can, and we must.

Shindell, Drew↗

Structural insights into isoform-specific RAS-PI3Kα interactions and the role of RAS in PI3Kα activation

Abstract Mutations in RAS and PI3Kα are major drivers of human cancer. Their interaction plays a crucial role in activating PI3Kα and amplifying the PI3K-AKT-mTOR pathway. Disrupting RAS-PI3Kα interaction enhances survival in lung and skin cancer models and reduces tumor growth and angiogenesis, although the structural details of this interaction remain unclear. Here, we present structures of KRAS, RRAS2, and MRAS bound to the catalytic subunit (p110α) of PI3Kα, elucidating the interaction interfaces and local conformational changes upon complex formation. Structural and mutational analyses highlighted key residues in RAS and PI3Kα impacting binding affinity and revealed isoform-specific differences at the interaction interface in RAS and PI3K isoforms, providing a rationale for their differential affinities. Notably, in the RAS-p110α complex structures, RAS interaction with p110α is limited to the RAS-binding domain and does not involve the kinase domain. This study underscores the pivotal role of the RAS-PI3Kα interaction in PI3Kα activation and provides a blueprint for designing PI3Kα isoform-specific inhibitors to disrupt this interaction.

Science & Technology - Other Topics↗

Total body calcium analysis

A technique to quantitate total body calcium in humans is developed. Total body neutron irradiation is utilized to produce argon 37. The radio argon, which diffuses into the blood stream and is excreted through the lungs, is recovered from the exhaled breath and counted inside a proportional detector. Emphasis is placed on: (1) measurement of the rate of excretion of radio argon following total body neutron irradiation; (2) the development of the radio argon collection, purification, and counting systems; and (3) development of a patient irradiation facility using a 14 MeV neutron generator. Results and applications are discussed in detail.

Lewellen, T. K.↗

Omics-Lethal Human Viruses, MERS-CoV Experiment MM001

The purpose of this experiment was to evaluate the host response to wild-type Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) virus infection. Sample data was obtained from primary mouse lung for mRNA, proteomics, lipidomics, and metabolomics expression analysis. Secondary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics, metabolomics, lipidomics, and transcriptomics dataset downloads each have a direct relationship to a primary sample submission corresponding to a specific MERS-CoV virus infection.

59 BASIC BIOLOGICAL SCIENCES↗

Dysregulation of lung epithelial cell homeostasis and immunity contributes to Middle East respiratory syndrome coronavirus disease severity

Coronaviruses (CoV) emerge suddenly from animal reservoirs to cause novel diseases in new hosts. Discovered in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic in camels in the Middle East and is continually causing local outbreaks and epidemics. While all three newly emerging human CoVs from the past 20 years (SARS-CoV, SARS-CoV-2, and MERS-CoV) cause respiratory disease, each CoV has unique host interactions that drive differential pathogeneses. To better understand the virus and host interactions driving lethal MERS-CoV infection, we performed a longitudinal multi-omics analysis of sublethal and lethal MERS-CoV infection in mice. Significant differences were observed in body weight loss, virus titers, and acute lung injury among lethal and sub-lethal virus doses. Virus-induced apoptosis of type I and II alveolar epithelial cells suggests that loss or dysregulation of these key cell populations was a major driver of severe disease. Omics analysis suggested differential pathogenesis was multi-factorial with clear differences among innate and adaptive immune pathways as well as those that regulate lung epithelial homeostasis. Infection of mice lacking functional T and B cells showed that adaptive immunity was important in controlling viral replication but also increased pathogenesis. In summary, we provide a high-resolution host response atlas for MERS-CoV infection and disease severity. Multi-omics studies of viral pathogenesis offer a unique opportunity to not only better understand the molecular mechanisms of disease but also to identify genes and pathways that can be exploited for therapeutic intervention all of which is important for our future pandemic preparedness.

MERS-CoV↗

Solar particle dose rate buildup and distribution in critical body organs

Human body organs have varying degrees of radiosensitivity as evidenced by radioepidemiologic tables. The major critical organs for both the male and female that have been identified include the lung, thyroid, stomach, and breast (female). Using computerized anatomical models of the 50th percentile United States Air Force male and female, we present the self-shielding effects of these various body organs and how the shielding effects change as the location (dose point) in the body varies. Several major solar proton events from previous solar cycles and several events from the current 22nd solar cycle have been analyzed. The solar particle event rise time, peak intensity, and decay time vary considerably from event to event. Absorbed dose and dose equivalent rate calculations and organ risk assessment data are presented for each critical body organ. These data are compared with the current NASA astronaut dose limits as recommended by the National Council on Radiation Protection and Measurements.

Atwell, William↗

Computational ranking identifies Plexin-B2 in circulating tumor cell clustering with monocytes in breast cancer metastasis

Abstract Multicellular circulating tumor cell (CTC) clusters can be up to 50 times more efficient than single CTCs in mediating viable metastasis. Here, combining computational ranking and functional determination, we identify the transmembrane protein Plexin-B2 (PLXNB2) as one of the top molecular targets associated with unfavorable distant metastasis-free survival, showing enriched expression in CTC clusters versus single CTCs from patients with advanced breast cancer (mostly female). Loss of PLXNB2 (Plxnb2) reduces the formation of homotypic tumor cell clusters and heterotypic tumor-myeloid cell clusters, reducing spontaneous metastases in female mice bearing human (mouse) breast cancer. Interactions of PLXNB2 with its ligands SEMA4C on tumor cells and SEMA4A on myeloid cells (monocytes) promote homotypic and heterotypic CTC cluster formation, respectively, thereby driving lung metastasis. Global proteomic analysis reveals downstream effectors of the PLXNB2 pathway associated with tumor cell clustering. Thus, PLXNB2 is a therapeutic target for preventing new metastasis in breast cancer.

Science & Technology - Other Topics↗

Mathematical modelling of a human external respiratory system

A closed system of algebraic and common differential equations solved by computer is investigated. It includes equations which describe the activity pattern of the respiratory center, the phrenic nerve, the thrust produced by the diaphragm as a function of the lung volume and discharge frequency of the phrenic nerve, as well as certain relations of the lung stretch receptors and chemoreceptors on various lung and blood characteristics, equations for lung biomechanics, pulmonary blood flow, alveolar gas exchange and capillary blood composition equations to determine various air and blood flow and gas exchange parameters, and various gas mixing and arterial and venous blood composition equations, to determine other blood, air and gas mixing characteristics. Data are presented by means of graphs and tables, and some advantages of this model over others are demonstrated by test results.

Source record↗

A susceptibility gene signature for ERBB2-driven mammary tumour development and metastasis in collaborative cross mice

Background: Deeper insights into ERBB2-driven cancers are essential to develop new treatment approaches for ERBB2+ breast cancers (BCs). We employed the Collaborative Cross (CC) mouse model to unearth genetic factors underpinning Erbb2-driven mammary tumour development and metastasis. Methods: 732 F1 hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains were monitored for mammary tumour phenotypes. GWAS pinpointed SNPs that influence various tumour phenotypes. Multivariate analyses and models were used to construct the polygenic score and to develop a mouse tumour susceptibility gene signature (mTSGS), where the corresponding human ortholog was identified and designated as hTSGS. The importance and clinical value of hTSGS in human BC was evaluated using public datasets, encompassing TCGA, METABRIC, GSE96058, and I-SPY2 cohorts. The predictive power of mTSGS for response to chemotherapy was validated in vivo using genetically diverse MMTV-Erbb2 mice. Findings: Distinct variances in tumour onset, multiplicity, and metastatic patterns were observed in F1-hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains. Besides lung metastasis, liver and kidney metastases emerged in specific CC strains. GWAS identified specific SNPs significantly associated with tumour onset, multiplicity, lung metastasis, and liver metastasis. Multivariate analyses flagged SNPs in 20 genes (Stx6, Ramp1, Traf3ip1, Nckap5, Pfkfb2, Trmt1l, Rprd1b, Rer1, Sepsecs, Rhobtb1, Tsen15, Abcc3, Arid5b, Tnr, Dock2, Tti1, Fam81a, Oxr1, Plxna2, and Tbc1d31) independently tied to various tumour characteristics, designated as a mTSGS. hTSGS scores (hTSGSS) based on their transcriptional level showed prognostic values, superseding clinical factors and PAM50 subtype across multiple human BC cohorts, and predicted pathological complete response independent of and superior to MammaPrint score in I-SPY2 study. The power of mTSGS score for predicting chemotherapy response was further validated in an in vivo mouse MMTV-Erbb2 model, showing that, like findings in human patients, mouse tumours with low mTSGS scores were most likely to respond to treatment. Interpretation: Our investigation has unveiled many new genes predisposing individuals to ERBB2-driven cancer. Translational findings indicate that hTSGS holds promise as a biomarker for refining treatment strategies for patients with BC.

60 APPLIED LIFE SCIENCES↗

Assessment of autonomic response by broad-band respiration

We present a technique for introducing broad-band respiratory perturbations so that the response characteristics of the autonomic nervous system can be determined noninvasively over a wide range of physiologically relevant frequencies. A subject's respiratory bandwidth was broadened by breathing on cue to a sequence of audible tones spaced by Poisson intervals. The transfer function between the respiratory input and the resulting instantaneous heart rate was then computed using spectral analysis techniques. Results using this method are comparable to those found using traditional techniques, but are obtained with an economy of data collection.

NASA Discipline Cardiopulmonary↗

Human α-defensin 5 suppressed colon cancer growth by targeting PI3K pathway

Defensins are highly conserved antimicrobial peptides, which ubiquitously expressed in different species. In addition to the functions in host defense, their aberrant expression have also been documented in cancerous tissue including breast cancer, lung caner and renal carcinoma etc. Whereas, roles of Defensin Alpha 5 (DEFA5) in colon cancer has not been explored. Bioinformatic analysis was used to study the expression of DEFA5 and its correlation with clinical outcomes; Western blot, qPCR, Co-immunoprecipitation, xenograft models were used to the study the molecular mechanism. Decreased expression of DEFA5 at protein level was observed in colon tissues. Colon cancer cell lines proliferation and colony formation capacity were significantly suppressed by DEFA5 overexpression. Moreover, in vivo tumor growth in nude mice was also suppressed by DEFA5 overexpression, suggesting a tumor suppressor role of DEFA5 in colon cancer. Mechanistically, DEFA5 directly binds to the subunits of PI3K complex, thus attenuates the downstream signaling transduction, leads to delayed cell growth and metastasis. Collectively, we concluded that DEFA5 showed an inhibitory effect in colon cancer cell growth and may serve as a potential tumor suppressor in colon cancer.

60 APPLIED LIFE SCIENCES↗