Infection of the murine placenta by Listeria monocytogenes induces sex-specific responses in the fetal brain.

BACKGROUND: Epidemiological data indicate that prenatal infection is associated with an increased risk of several neurodevelopmental disorders in the progeny. These disorders display sex differences in presentation. The role of the placenta in the sex-specificity of infection-induced neurodevelopmental abnormalities is not well-defined. We used an imaging-based animal model of the bacterial pathogen Listeria monocytogenes to identify sex-specific effects of placental infection on neurodevelopment of the fetus. METHODS: Pregnant CD1 mice were infected with a bioluminescent strain of Listeria on embryonic day 14.5 (E14.5). Excised fetuses were imaged on E18.5 to identify the infected placentas. The associated fetal brains were analyzed for gene expression and altered brain structure due to infection. The behavior of adult offspring affected by prenatal Listeria infection was analyzed. RESULTS: Placental infection induced sex-specific alteration of gene expression patterns in the fetal brain and resulted in abnormal cortical development correlated with placental infection levels. Furthermore, male offspring exhibited abnormal social interaction, whereas females exhibited elevated anxiety. CONCLUSION: Placental infection by Listeria induced sex-specific abnormalities in neurodevelopment of the fetus. Prenatal infection also affected the behavior of the offspring in a sex-specific manner. IMPACT: Placental infection with Listeria monocytogenes induces sexually dichotomous gene expression patterns in the fetal brains of mice. Abnormal cortical lamination is correlated with placental infection levels. Placental infection results in autism-related behavior in male offspring and heightened anxiety levels in female offspring.

Long-Term Trend Analysis in the Solar Radiation and Climate Experiment (SORCE)/Spectral Irradiance Monitor (SIM).

The Solar Radiation and Climate Experiment/Spectral Irradiance Monitor (SORCE/SIM) instrument was launched on 25 January 2003 with mission termination occurring on 25 February 2020. The SORCE/SIM provides a unique data set of the variability in solar spectral irradiance (SSI) during the descending phase of Solar Cycle 23 (SC23) from April 2003 to February 2009, the weaker solar-maximum conditions of SC24, and the quiescent SC24/SC25 minimum. The determination of the magnitude and phase of SSI variations rely on the unambiguous determination of the effects of the space environment and solar-exposure-related degradation mechanisms. The instrument-only corrections for SIM are based on a comparison of two functionally identical (mirror image) prism spectrometers with four independent detectors in each spectrometer channel. The degradation correction is strictly instrumental in its methodology and makes no assumptions about the magnitude, slope, or wavelength dependence of the SSI variability.

Solar-Cycle Variability Results from the Solar Radiation and Climate Experiment (SORCE) Mission.

The Solar Radiation and Climate Experiment (SORCE) was a NASA mission that operated from 2003 to 2020 to provide key climate-monitoring measurements of total solar irradiance (TSI) and solar spectral irradiance (SSI). This 17-year mission made TSI and SSI observations during the declining phase of Solar Cycle 23, during all of Solar Cycle 24, and at the very beginning of Solar Cycle 25. The SORCE solar-variability results include comparisons of the solar irradiance observed during Solar Cycles 23 and 24 and the solar-cycle minima levels in 2008 - 2009 and 2019 - 2020. The differences between these two minima are very small and are not significantly above the estimate of instrument stability over the 11-year period. There are differences in the SSI variability for Solar Cycles 23 and 24, notably for wavelengths longer than 250 nm. Consistency comparisons with SORCE variability on solar-rotation timescales and solar-irradiance model predictions suggest that the SORCE Solar Cycle 24 SSI results might be more accurate than the SORCE Solar Cycle 23 results. The SORCE solar-variability results have been useful for many Sun-climate studies and will continue to serve as a reference for comparisons with future missions studying solar variability.

Overview of the Solar Radiation and Climate Experiment (SORCE) Seventeen-Year Mission.

The Solar Radiation and Climate Experiment (SORCE) was a NASA mission that operated from 2003 to 2020 to provide key climate-monitoring measurements of total solar irradiance (TSI) and solar spectral irradiance (SSI). Three important accomplishments of the SORCE mission are i) the continuation of the 42-year-long TSI climate data record, ii) the continuation of the ultraviolet SSI record, and iii) the initiation of the near-ultraviolet, visible, and near-infrared SSI records. All of the SORCE instruments functioned well over the 17-year mission, which far exceeded its five-year prime mission goal. The SORCE spacecraft, having mostly redundant subsystems, was also robust over the mission. The end of the SORCE mission was a planned passivation of the spacecraft following a successful two-year overlap with the NASA Total and Spectral Solar Irradiance Sensor (TSIS) mission, which continues the TSI and SSI climate records. There were a couple of instrument anomalies and a few spacecraft anomalies during SORCE's long mission, but operational changes and updates to flight software enabled SORCE to remain productive to the end of its mission. The most challenging of the anomalies was the degradation of the battery capacity that began to impact operations in 2009 and was the cause for the largest SORCE data gap (August 2013 - February 2014). An overview of the SORCE mission is provided with a couple of science highlights and a discussion of flight anomalies that impacted the solar observations. Companion articles about the SORCE instruments and their final science data-processing algorithms provide additional details about the instrument measurements over the duration of the mission.

The Instruments and Capabilities of the Miniature X-Ray Solar Spectrometer (MinXSS) CubeSats.

The Miniature X-ray Solar Spectrometer (MinXSS) CubeSat is the first solar science oriented CubeSat mission flown for the NASA Science Mission Directorate, with the main objective of measuring the solar soft X-ray (SXR) flux and a science goal of determining its influence on Earth's ionosphere and thermosphere. These observations can also be used to investigate solar quiescent, active region, and flare properties. The MinXSS X-ray instruments consist of a spectrometer, called X123, with a nominal 0.15 keV full-width at half-maximum (FWHM) resolution at 5.9 keV and a broadband X-ray photometer, called XP. Both instruments are designed to obtain measurements from 0.5 - 30 keV at a nominal time cadence of 10 s. A description of the MinXSS instruments, performance capabilities, and relation to the Geostationary Operational Environmental Satellite (GOES) 0.1 - 0.8 nm flux is given in this article. Early MinXSS results demonstrate the capability of measuring variations of the solar spectral soft X-ray (SXR) flux between 0.8 - 12 keV from at least GOES A5-M5 ( 5 × 10 - 8 - 5 × 10 - 5 W m - 2 ) levels and of inferring physical properties (temperature and emission measure) from the MinXSS data alone. Moreover, coronal elemental abundances can be inferred, specifically for Fe, Ca, Si, Mg, S, Ar, and Ni, when the count rate is sufficiently high at each elemental spectral feature. Additionally, temperature response curves and emission measure loci demonstrate the MinXSS sensitivity to plasma emission at different temperatures. MinXSS observations coupled with those from other solar observatories can help address some of the most compelling questions in solar coronal physics. Finally, simultaneous observations by MinXSS and the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) can provide the most spectrally complete soft X-ray solar flare photon flux measurements to date.

Decoupling Solar Variability and Instrument Trends Using the Multiple Same-Irradiance-Level (MuSIL) Analysis Technique.

The solar spectral irradiance (SSI) dataset is a key record for studying and understanding the energetics and radiation balance in Earth's environment. Understanding the long-term variations of the SSI over timescales of the 11-year solar activity cycle and longer is critical for many Sun-Earth research topics. Satellite measurements of the SSI have been made since the 1970s, most of them in the ultraviolet, but recently also in the visible and near-infrared. A limiting factor for the accuracy of previous solar variability results is the uncertainties for the instrument degradation corrections, which need fairly large corrections relative to the amount of solar cycle variability at some wavelengths. The primary objective of this investigation has been to separate out solar cycle variability and any residual uncorrected instrumental trends in the SSI measurements from the Solar Radiation and Climate Experiment (SORCE) mission and the Thermosphere, Mesosphere, Ionosphere, Energetic, and Dynamics (TIMED) mission. A new technique called the Multiple Same-Irradiance-Level (MuSIL) analysis has been developed, which examines an SSI time series at different levels of solar activity to provide long-term trends in an SSI record, and the most common result is a downward trend that most likely stems from uncorrected instrument degradation. This technique has been applied to each wavelength in the SSI records from SORCE (2003 - present) and TIMED (2002 - present) to provide new solar cycle variability results between 27 nm and 1600 nm with a resolution of about 1 nm at most wavelengths. This technique, which was validated with the highly accurate total solar irradiance (TSI) record, has an estimated relative uncertainty of about 5% of the measured solar cycle variability. The MuSIL results are further validated with the comparison of the new solar cycle variability results from different solar cycles.

The solar magnetic activity band interaction and instabilities that shape quasi-periodic variability.

Solar magnetism displays a host of variational timescales of which the enigmatic 11-year sunspot cycle is most prominent. Recent work has demonstrated that the sunspot cycle can be explained in terms of the intra- and extra-hemispheric interaction between the overlapping activity bands of the 22-year magnetic polarity cycle. Those activity bands appear to be driven by the rotation of the Sun's deep interior. Here we deduce that activity band interaction can qualitatively explain the 'Gnevyshev Gap'­a well-established feature of flare and sunspot occurrence. Strong quasi-annual variability in the number of flares, coronal mass ejections, the radiative and particulate environment of the heliosphere is also observed. We infer that this secondary variability is driven by surges of magnetism from the activity bands. Understanding the formation, interaction and instability of these activity bands will considerably improve forecast capability in space weather and solar activity over a range of timescales.

A Different View of Solar Spectral Irradiance Variations: Modeling Total Energy over Six-Month Intervals.

A different approach to studying solar spectral irradiance (SSI) variations, without the need for long-term (multi-year) instrument degradation corrections, is examining the total energy of the irradiance variation during 6-month periods. This duration is selected because a solar active region typically appears suddenly and then takes 5 to 7 months to decay and disperse back into the quiet-Sun network. The solar outburst energy, which is defined as the irradiance integrated over the 6-month period and thus includes the energy from all phases of active region evolution, could be considered the primary cause for the irradiance variations. Because solar cycle variation is the consequence of multiple active region outbursts, understanding the energy spectral variation may provide a reasonable estimate of the variations for the 11-year solar activity cycle. The moderate-term (6-month) variations from the Solar Radiation and Climate Experiment (SORCE) instruments can be decomposed into positive (in-phase with solar cycle) and negative (out-of-phase) contributions by modeling the variations using the San Fernando Observatory (SFO) facular excess and sunspot deficit proxies, respectively. These excess and deficit variations are fit over 6-month intervals every 2 months over the mission, and these fitted variations are then integrated over time for the 6-month energy. The dominant component indicates which wavelengths are in-phase and which are out-of-phase with solar activity. The results from this study indicate out-of-phase variations for the 1400 - 1600 nm range, with all other wavelengths having in-phase variations.

Influence of solar variability on the infrared radiative cooling of the thermosphere from 2002 to 2014.

Infrared radiative cooling of the thermosphere by carbon dioxide (CO2, 15 µm) and by nitric oxide (NO, 5.3 µm) has been observed for 12 years by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on the Thermosphere-Ionosphere-Mesosphere Energetics and Dynamics satellite. For the first time we present a record of the two most important thermospheric infrared cooling agents over a complete solar cycle. SABER has documented dramatic variability in the radiative cooling on time scales ranging from days to the 11 year solar cycle. Deep minima in global mean vertical profiles of radiative cooling are observed in 2008-2009. Current solar maximum conditions, evidenced in the rates of radiative cooling, are substantially weaker than prior maximum conditions in 2002-2003. The observed changes in thermospheric cooling correlate well with changes in solar ultraviolet irradiance and geomagnetic activity during the prior maximum conditions. NO and CO2 combine to emit 7 × 1018 more Joules annually at solar maximum than at solar minimum. KEY POINTS: First record of thermospheric IR cooling rates over a complete solar cycleIR cooling in current solar maximum conditions much weaker than prior maximumVariability in thermospheric IR cooling observed on scale of days to 11 years.

Dysregulation of the Mammalian Target of Rapamycin and p27Kip1 Promotes Intimal Hyperplasia in Diabetes Mellitus.

The proliferation and migration of vascular smooth muscle cells (VSMCs) in the intima of an artery, known as intimal hyperplasia, is an important component of cardiovascular diseases. This is seen most clearly in the case of in-stent restenosis, where drug eluting stents are used to deliver agents that prevent VSMC proliferation and migration. One class of agents that are highly effective in the prevention of in-stent restenosis is the mammalian Target of Rapamycin (mTOR) inhibitors. Inhibition of mTOR blocks protein synthesis, cell cycle progression, and cell migration. Key to the effects on cell cycle progression and cell migration is the inhibition of mTOR-mediated degradation of p27Kip1 protein. p27Kip1 is a cyclin dependent kinase inhibitor that is elevated in quiescent VSMCs and inhibits the G1 to S phase transition and cell migration. Under normal conditions, vascular injury promotes degradation of p27Kip1 protein in an mTOR dependent manner. Recent reports from our lab suggest that in the presence of diabetes mellitus, elevation of extracellular signal response kinase activity may promote decreased p27Kip1 mRNA and produce a relative resistance to mTOR inhibition. Here we review these findings and their relevance to designing treatments for cardiovascular disease in the presence of diabetes mellitus.

Loss of canonical insulin signaling accelerates vascular smooth muscle cell proliferation and migration through changes in p27Kip1 regulation.

Insulin resistance is associated with an accelerated rate of atherosclerosis. Vascular smooth muscle cell (VSMC) migration and proliferation are important components of atherosclerosis. To elucidate the effects of the loss of normal insulin receptor (IR) signaling on VSMC function, we compared the proliferation and migration of murine VSMCs lacking the IR (L2-VSMCs) with wild type (WT-VSMCs). We also examined changes in the response of L2-VSMCs to insulin stimulation and to inhibition of the mammalian target of rapamycin (mTOR), a kinase critical in VSMC proliferation and migration. The L2-VSMCs exhibit greater proliferation and migration rates compared with WT-VSMCs. L2-VSMCs also exhibit a resistance to the effects of rapamycin, an mTOR inhibitor, on proliferation, migration, and cell cycle progression. The resistance to mTOR inhibition is coupled with a loss of effect on the cyclin-dependent kinase inhibitor p27(Kip1), an inhibitor of cell cycle progression and VSMC migration. In response to stimulation with physiological insulin, the L2-VSMCs exhibit a loss of Akt phosphorylation and a significantly increased activation of the ERK-1/2 compared with WT-VSMCs. Insulin stimulation also decreased p27(Kip1) mRNA in L2-VSMCs but not in WT-VSMCs. The effect of insulin on p27(Kip1) mRNA was blocked by pretreatment with an ERK-1/2 pathway inhibitor. We conclude that loss of canonical insulin signaling results in increased ERK-1/2 activation in response to physiological insulin that decreases p27(Kip1) mRNA. These data demonstrate a potential mechanism where changes in IR signaling could lead to a decrease in p27(Kip1), accelerating VSMC proliferation and migration.

Summary statement: appropriate medical care for the secondary school-aged athlete.

OBJECTIVE: To present the recommendations made by the Appropriate Medical Care for Secondary School-Aged Athletes Task Force and to summarize the subsequent monograph developed around 11 consensus points. DATA SOURCES: The MEDLINE, CINAHL, and SportDiscus databases were searched for relevant literature regarding secondary school-aged athletes; health care administration; preparticipation physical examination; facilities; athletic equipment; emergency action planning; environmental conditions; recognition, evaluation, and treatment of injuries; rehabilitation and reconditioning; psychosocial consultation; nutrition; and prevention strategies. CONCLUSIONS AND RECOMMENDATIONS: Organizations that sponsor athletic programs for secondary school-aged athletes should establish an athletic health care team to ensure that appropriate medical care is provided to all participants. The 11 consensus points provide a framework-one that is supported by the medical literature and case law-for the development of an athletic health care team and for assigning responsibilities to the team, administrators, and staff members of institutions sponsoring secondary school and club-level athletic programs.

Doubly ionized carbon observed in the plasma tail of comet Kudo-Fujikawa.

Comet C/2002 X5 (Kudo-Fujikawa) was observed near its perihelion of 0.19 astronomical unit by the Ultraviolet Coronagraph Spectrometer aboard the Solar and Heliospheric Observatory spacecraft. Images of the comet reconstructed from high-resolution spectra reveal a quasi-spherical cloud of neutral hydrogen and a variable tail of C+ and C2+ that disconnects from the comet and subsequently regenerates. The high abundance of C2+ and C+, at least 24% relative to water, cannot be explained by photodissociation of carbon monoxide and is instead attributed to the evaporation and subsequent photoionization of atomic carbon from organic refractory compounds present in the cometary dust grains. This result serves to strengthen the connection between comets and the material from which the Solar System formed.