Animal models of fetal growth restriction: Considerations for translational medicine.

Fetal growth restriction (FGR) is the failure of a fetus to reach its full genetic growth potential. It occurs in up to 8% of pregnancies, and after premature birth is the second leading cause of infant mortality and morbidity. There is no treatment currently available for FGR. Its primary cause, when not attributable to structural or genetic defects of the fetus, is 'placental insufficiency'. This broad definition covers the inability of the fetus to acquire sufficient nutrients and oxygen, and is influenced by a number of factors including altered maternal or fetal blood flow, reduced nutrient transport or changes in the placenta such as increased barrier thickness inhibiting nutrient transfer. For those researchers studying FGR and developing new therapies, choosing an animal model is a crucial consideration. It is vital to clearly frame the question being asked, as this will impact the factor influencing fetal nutrient delivery in the model, and will also affect the applicability of the results to the human condition. This review examines the range of in vivo models of FGR available for those engaged in translational research

Latitudinal, vertical, and seasonal variations of C-1-C-4 alkyl nitrates in the troposphere over the Pacific Ocean during PEM-Tropics A and B: Oceanic and continental sources

We present concentration distributions of C1‐C4 alkyl nitrates observed during the NASA airborne campaigns Pacific Exploratory Mission (PEM) ‐Tropics A (September–October 1996) and PEM‐Tropics B (March–April 1999). The total geographic range for PEM‐Tropics A was 45°N–72°S latitude and 153°E–75°W longitude, and for PEM‐Tropics B was 40°N–36°S latitude and 149°E–75°W longitude. The maximum altitude for these missions was 12 km. These experiments provide the most extensive set of tropospheric measurements collected to date over the tropical Pacific Ocean. We observed high methyl nitrate (MeONO2, CH3ONO2) mixing ratios (approximately 50 pptv) at low altitudes in a latitude band between 8°N to 13°S stretching across the equatorial Pacific, illustrating the oceanic source of MeONO2. This source may be associated with the high‐nutrient, low‐chlorophyll character of equatorial Pacific waters. We discuss MeONO2 and ethyl nitrate (EtONO2, C2H5ONO2), whose abundance is dominated by equatorial oceanic sources, 2‐Propyl nitrate (2‐PrONO2, 2‐C3H7ONO2), which has significant oceanic and northern hemispheric (NH) sources associated with urban/industrial hydrocarbon emissions, and 2‐butyl nitrate (2‐BuONO2 2‐C4H8ONO2), which has mostly NH sources. PEM‐Tropics A and B resulted in remarkably similar equatorial mixing ratios. The excellent correlations between MeONO2 and the other alkyl nitrates in this region produced comparable correlation slopes between the two expeditions. By contrast, NH air masses influenced by urban/industrial emissions typically exhibited much lower MeONO2:EtONO2, MeONO2:2‐PrONO2, and MeONO2:2‐BuONO2 ratios. These relationships can be useful as a diagnostic of air mass origin. North of 10°N, the springtime PEM‐Tropics B mixing ratios of C2‐C4 alkyl nitrates were many‐fold higher at low‐mid altitudes than for late summer PEM‐Tropics A, consistent with strong continental outflow of NMHC precursors during spring

Workshop on Two-Phase Fluid Behavior in a Space Environment

The Workshop was successful in achieving its main objective of identifying a large number of technical issues relating to the design of two-phase systems for space applications. The principal concern expressed was the need for verified analytical tools that will allow an engineer to confidently design a system to a known degree of accuracy. New and improved materials, for such applications as thermal storage and as heat transfer fluids, were also identified as major needs. In addition to these research efforts, a number of specific hardware needs were identified which will require development. These include heat pumps, low weight radiators, advanced heat pipes, stability enhancement devices, high heat flux evaporators, and liquid/vapor separators. Also identified was the need for a centralized source of reliable, up-to-date information on two-phase flow in a space environment

Hydroxyl concentration estimates in the sunlit snowpack at Summit, Greenland

Experiments were performed at Summit, Greenland (72°34′ N, 38°29′ W) to investigate hydroxyl mixing ratios in the sunlit surface snowpack (or firn). We added a carefully selected mixture of hydrocarbon gases (with a wide range of hydroxyl reactivities) to a UV and visible light transparent flow chamber containing undisturbed natural firn. The relative decrease in mixing ratios of these gases allowed estimation of the lower limit mixing ratio of hydroxyl radicals in the near-surface firn pore spaces. Hydroxyl mixing ratios in the firn air followed a diurnal cycle in summer 2003 (10-12 July), with peak values of more than 3.2×106 molecules cm-3 between 13:00 and 16:00 local time. The minimum value estimated was 1.1×106 molecules cm-3 at 20:00 local time. Results during spring of 2004 showed lower, but rapidly increasing, peak hydroxyl mixing ratios of 1.1×106 molecules cm-3 in the early afternoon on 15 April and 1.5×106 molecules cm-3 on 1 May. Our firn hydroxyl estimates were similar to directly measured above-snow ambient levels during the spring field season, but were only about 30% of ambient levels during summer. © 2007 Elsevier Ltd. All rights reserved

Large-scale latitudinal and vertical distributions of NMHCs and selected halocarbons in the troposphere over the Pacific Ocean during the March-April 1999 Pacific Exploratory Mission (PEM-Tropics B)

Nonmethane hydrocarbons (NMHCs) and selected halocarbons were measured in whole air samples collected over the remote Pacific Ocean during NASA's Global Tropospheric Experiment (GTE) Pacific Exploratory Mission-Tropics B (PEM-Tropics B) in March and early April 1999. The large-scale spatial distributions of NMHCs and C2Cl4 reveal a much more pronounced north-south interhemispheric gradient, with higher concentrations in the north and lower levels in the south, than for the late August to early October 1996 PEM-Tropics A experiment. Strong continental outflow and winter-long accumulation of pollutants led to seasonally high Northern Hemisphere trace gas levels during PEM-Tropics B. Observations of enhanced levels of Halon 1211 (from developing Asian nations such as the PRC) and CH3Cl (from SE Asian biomass burning) support a significant southern Asian influence at altitudes above 1 km and north of 10° N. By contrast, at low altitude over the North Pacific the dominance of urban/industrial tracers, combined with low levels of Halon 1211 and CH3Cl, indicate a greater influence from developed nations such as Japan, Europe, and North America. Penetration of air exhibiting aged northern hemisphere characteristics was frequently observed at low altitudes over the equatorial central and western Pacific south to ∼5° S. The relative lack of southern hemisphere biomass burning sources and the westerly position of the South Pacific convergence zone contributed to significantly lower PEM-Tropics B mixing ratios of the NMHCs and CH3Cl south of 10° S compared to PEM-Tropics A. Therefore the trace gas composition of the South Pacific troposphere was considerably more representative of minimally polluted tropospheric conditions during PEM-Tropics B. Copyright 2001 by the American Geophysical Union

NMHCs and halocarbons in Asian continental outflow during the Transport and Chemical Evolution over the Pacific (TRACE-P) Field Campaign: Comparison with PEM-West B

We present an overview of the spatial distributions of nonmethane hydrocarbons (NMHCs) and halocarbons observed over the western north Pacific as part of the NASA GTE Transport and Chemical Evolution over the Pacific (TRACE‐P) airborne field campaign (February–April 2001). The TRACE‐P data are compared with earlier measurements from the Pacific Rim during the Pacific Exploratory Mission‐West B (PEM‐West B), which took place in February–March 1994, and with emission inventory data for 2000. Despite the limited spatial and temporal data coverage inherent to airborne sampling, mean levels of the longer‐lived NMHCs (including ethane, ethyne, and benzene) were remarkably similar to our results during the PEM‐West B campaign. By comparison, mixing ratios of the fire extinguisher Halon‐1211 (CF2ClBr) increased by about 50% in the period between 1994 and 2001. Southern China (south of 35°N), and particularly the Shanghai region, appears to have been a substantial source of Halon‐1211 during TRACE‐P. Our previous analysis of the PEM‐West B data employed methyl chloroform (CH3CCl3) as a useful industrial tracer. However, regulations have reduced its emissions to the extent that its mixing ratio during TRACE‐P was only one‐third of that measured in 1994. Methyl chloroform mixing ratio “hot spots,” indicating regions downwind of continuing emissions, included outflow from the vicinity of Shanghai, China, but particularly high emission ratios relative to CO were observed close to Japan and Korea. Tetrachloroethene (C2Cl4) levels have also decreased significantly, especially north of 25°N, but this gas still remains a useful indicator of northern industrial emissions. Methyl bromide (CH3Br) levels were systematically 1–2 pptv lower from 1994 to 2001, in accord with recent reports. However, air masses that had been advected over Japan and/or South Korean port cities typically exhibited elevated levels of CH3Br. As a consequence, emissions of CH3Br from Japan and Korea calculated employing CH3Br/CO ratios and scaled to CO emission inventory estimates, were almost as large as for all of south China (south of 35°N). Total east Asian emissions of CH3Br and CH3Cl were estimated to be roughly 4.7 Gg/yr and 167 Gg/yr, respectively, in 2001

S100A8/A9 regulates CD11b expression and neutrophil recruitment during chronic tuberculosis

Neutrophil accumulation is associated with lung pathology during active tuberculosis (ATB). However, the molecular mechanism or mechanisms by which neutrophils accumulate in the lung and contribute to TB immunopathology are not fully delineated. Using the well-established mouse model of TB, our new data provide evidence that the alarmin S100A8/A9 mediates neutrophil accumulation during progression to chronic TB. Depletion of neutrophils or S100A8/A9 deficiency resulted in improved Mycobacterium tuberculosis (Mtb) control during chronic but not acute TB. Mechanistically, we demonstrate that, following Mtb infection, S100A8/A9 expression is required for upregulation of the integrin molecule CD11b specifically on neutrophils, mediating their accumulation during chronic TB disease. These findings are further substantiated by increased expression of S100A8 and S100A9 mRNA in whole blood in human TB progressors when compared with nonprogressors and rapidly decreased S100A8/A9 protein levels in the serum upon TB treatment. Furthermore, we demonstrate that S100A8/A9 serum levels along with chemokines are useful in distinguishing between ATB and asymptomatic Mtb-infected latent individuals. Thus, our results support targeting S100A8/A9 pathways as host-directed therapy for TB

Development and testing of a spray-dried tuberculosis vaccine candidate in a mouse model

Converting a vaccine into a thermostable dry powder is advantageous as it reduces the resource burden linked with the cold chain and provides flexibility in dosage and administration through different routes. Such a dry powder presentation may be especially useful in the development of a vaccine towards the respiratory infectious disease tuberculosis (TB). This study assesses the immunogenicity and protective efficacy of spray-dried ID93+GLA-SE, a promising TB vaccine candidate, agains