Neuroanatomic Correlates of Female Sexual Dysfunction in Multiple Sclerosis

OBJECTIVE: This study intended to determine associations between alterations of female sexual arousal as well as vaginal lubrication and the site of cerebral multiple sclerosis (MS) lesions. METHODS: In 44 women with MS (mean age: 36.5 ± 9.9 years), we assessed their medical history and evaluated sexual function using the Female Sexual Function Index scores for arousal and vaginal lubrication. We determined potential confounding factors of sexual dysfunction: age; disease duration; physical disability; depression; bladder or urinary dysfunction; and total volume of cerebral lesions. Arousal and lubrication scores were correlated with one another and with potential confounding factors. Cerebral MS lesions were recorded on imaging scans. A voxel-based lesion symptom mapping (VLSM) analysis adjusted for confounding variables was performed correlating cerebral sites of MS lesions with arousal and lubrication scores. RESULTS: Decreased arousal scores correlated with decreased lubrication scores; decreased lubrication scores were associated with bladder or urinary symptoms. Arousal and lubrication scores were not associated with any other variables. Multivariate VLSM analysis, including arousal and lubrication scores as covariables of interest, showed right occipital lesions associated with impaired arousal and left insular lesions associated with decreased lubrication. Impaired lubrication remained associated with left insular lesions after adjustment for bladder or urinary dysfunction. INTERPRETATION: Our data indicate that impaired female sexual arousal is associated with MS lesions in the occipital region, integrating visual information and modulating attention toward visual input. Impaired lubrication correlated with lesions in the left insular region, contributing to mapping and generating visceral arousal states

Competition between Magnetic and Structural Transition in CrN

CrN is observed to undergo a paramagnetic to antiferromagnetic transition accompanied by a shear distortion from cubic NaCl-type to orthorhombic structure. Our first-principle plane wave and ultrasoft pseudopotential calculations confirm that the distorted antiferromagnetic phase with spin configuration arranged in double ferromagnetic sheets along [110] is the most stable. Antiferromagnetic ordering leads to a large depletion of states around Fermi level, but it does not open a gap. Simultaneous occurence of structural distortion and antiferromagnetic order is analyzed.Comment: 10 pages, 10 figure

Temporal Pattern of ICAM-I Mediated Regulatory T Cell Recruitment to Sites of Inflammation in Adoptive Transfer Model of Multiple Sclerosis

Migration of immune cells to the target organ plays a key role in autoimmune disorders like multiple sclerosis (MS). However, the exact underlying mechanisms of this active process during autoimmune lesion pathogenesis remain elusive. To test if pro-inflammatory and regulatory T cells migrate via a similar molecular mechanism, we analyzed the expression of different adhesion molecules, as well as the composition of infiltrating T cells in an in vivo model of MS, adoptive transfer experimental autoimmune encephalomyelitis in rats. We found that the upregulation of ICAM-I and VCAM-I parallels the development of clinical disease onset, but persists on elevated levels also in the phase of clinical remission. However, the composition of infiltrating T cells found in the developing versus resolving lesion phase changed over time, containing increased numbers of regulatory T cells (FoxP3) only in the phase of clinical remission. In order to test the relevance of the expression of cell adhesion molecules, animals were treated with purified antibodies to ICAM-I and VCAM-I either in the phase of active disease or in early remission. Treatment with a blocking ICAM-I antibody in the phase of disease progression led to a milder disease course. However, administration during early clinical remission aggravates clinical symptoms. Treatment with anti-VCAM-I at different timepoints had no significant effect on the disease course. In summary, our results indicate that adhesion molecules are not only important for capture and migration of pro-inflammatory T cells into the central nervous system, but also permit access of anti-inflammatory cells, such as regulatory T cells. Therefore it is likely to assume that intervention at the blood brain barrier is time dependent and could result in different therapeutic outcomes depending on the phase of CNS lesion development

Challenges associated with modeling low-oxygen waters in Chesapeake Bay: a multiple model comparison

As three-dimensional (3-D) aquatic ecosystem models are used more frequently for operational water quality forecasts and ecological management decisions, it is important to understand the relative strengths and limitations of existing 3-D models of varying spatial resolution and biogeochemical complexity. To this end, 2-year simulations of the Chesapeake Bay from eight hydrodynamic-oxygen models have been statistically compared to each other and to historical monitoring data. Results show that although models have difficulty resolving the variables typically thought to be the main drivers of dissolved oxygen variability (stratification, nutrients, and chlorophyll), all eight models have significant skill in reproducing the mean and seasonal variability of dissolved oxygen. In addition, models with constant net respiration rates independent of nutrient supply and temperature reproduced observed dissolved oxygen concentrations about as well as much more complex, nutrient-dependent biogeochemical models. This finding has significant ramifications for short-term hypoxia forecasts in the Chesapeake Bay, which may be possible with very simple oxygen parameterizations, in contrast to the more complex full biogeochemical models required for scenario-based forecasting. However, models have difficulty simulating correct density and oxygen mixed layer depths, which are important ecologically in terms of habitat compression. Observations indicate a much stronger correlation between the depths of the top of the pycnocline and oxycline than between their maximum vertical gradients, highlighting the importance of the mixing depth in defining the region of aerobic habitat in the Chesapeake Bay when low-oxygen bottom waters are present. Improvement in hypoxia simulations will thus depend more on the ability of models to reproduce the correct mean and variability of the depth of the physically driven surface mixed layer than the precise magnitude of the vertical density gradient

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis

The first widespread solar energetic particle event of solar cycle 25 on 2020 November 29 : Shock wave properties and the wide distribution of solar energetic particles

Context. On 2020 November 29, an eruptive event occurred in an active region located behind the eastern solar limb as seen from Earth. The event consisted of an M4.4 class flare, a coronal mass ejection, an extreme ultraviolet (EUV) wave, and a white-light (WL) shock wave. The eruption gave rise to the first widespread solar energetic particle (SEP) event of solar cycle 25, which was observed at four widely separated heliospheric locations (similar to 230 degrees). Aims. Our aim is to better understand the source of this widespread SEP event, examine the role of the coronal shock wave in the wide distribution of SEPs, and investigate the shock wave properties at the field lines magnetically connected to the spacecraft. Methods. Using EUV and WL data, we reconstructed the global three-dimensional structure of the shock in the corona and computed its kinematics. We determined the magnetic field configurations in the corona and interplanetary space, inferred the magnetic connectivity of the spacecraft with the shock surface, and derived the evolution of the shock parameters at the connecting field lines. Results. Remote sensing observations show formation of the coronal shock wave occurring early during the eruption, and its rapid propagation to distant locations. The results of the shock wave modelling show multiple regions where a strong shock has formed and efficient particle acceleration is expected to take place. The pressure/shock wave is magnetically connected to all spacecraft locations before or during the estimated SEP release times. The release of the observed near-relativistic electrons occurs predominantly close to the time when the pressure/shock wave connects to the magnetic field lines or when the shock wave becomes supercritical, whereas the proton release is significantly delayed with respect to the time when the shock wave becomes supercritical, with the only exception being the proton release at the Parker Solar Probe. Conclusions. Our results suggest that the shock wave plays an important role in the spread of SEPs. Supercritical shock regions are connected to most of the spacecraft. The particle increase at Earth, which is barely connected to the wave, also suggests that the cross-field transport cannot be ignored. The release of energetic electrons seems to occur close to the time when the shock wave connects to, or becomes supercritical at, the field lines connecting to the spacecraft. Energetic protons are released with a time-delay relative to the time when the pressure/shock wave connects to the spacecraft locations. We attribute this delay to the time that it takes for the shock wave to accelerate protons efficiently.Peer reviewe

Housing Conditions Differentially Affect Physiological and Behavioural Stress Responses of Zebrafish, as well as the Response to Anxiolytics

Zebrafish are a widely utilised animal model in developmental genetics, and owing to recent advances in our understanding of zebrafish behaviour, their utility as a comparative model in behavioural neuroscience is beginning to be realised. One widely reported behavioural measure is the novel tank-diving assay, which has been often cited as a test of anxiety and stress reactivity. Despite its wide utilisation, and various validations against anxiolytic drugs, reporting of pre-test housing has been sparse in the literature. As zebrafish are a shoaling species, we predicted that housing environment would affect their stress reactivity and, as such, their response in the tank-diving procedure. In our first experiment, we tested various aspects of housing (large groups, large groups with no contact, paired, visual contact only, olfactory contact only) and found that the tank diving response was mediated by visual contact with conspecifics. We also tested the basal cortisol levels of group and individually housed fish, and found that individually housed individuals have lower basal cortisol levels. In our second experiment we found ethanol appeared to have an anxiolytic effect with individually housed fish but not those that were group housed. In our final experiment, we examined the effects of changing the fishes' water prior to tank diving as an additional acclimation procedure. We found that this had no effect on individually housed fish, but appeared to affect the typical tank diving responses of the group housed individuals. In conclusion, we demonstrate that housing represents an important factor in obtaining reliable data from this methodology, and should be considered by researchers interested in comparative models of anxiety in zebrafish in order to refine their approach and to increase the power in their experiments

4pi Models of CMEs and ICMEs

Coronal mass ejections (CMEs), which dynamically connect the solar surface to the far reaches of interplanetary space, represent a major anifestation of solar activity. They are not only of principal interest but also play a pivotal role in the context of space weather predictions. The steady improvement of both numerical methods and computational resources during recent years has allowed for the creation of increasingly realistic models of interplanetary CMEs (ICMEs), which can now be compared to high-quality observational data from various space-bound missions. This review discusses existing models of CMEs, characterizing them by scientific aim and scope, CME initiation method, and physical effects included, thereby stressing the importance of fully 3-D ('4pi') spatial coverage.Comment: 14 pages plus references. Comments welcome. Accepted for publication in Solar Physics (SUN-360 topical issue

The Effect of Proton Temperature Anisotropy on the Solar Minimum Corona and Wind

A semi-empirical, axisymmetric model of the solar minimum corona is developed by solving the equations for conservation of mass and momentum with prescribed anisotropic temperature distributions. In the high-latitude regions, the proton temperature anisotropy is strong and the associated mirror force plays an important role in driving the fast solar wind; the critical point where the outflow velocity equals the parallel sound speed is reached already at 1.5 Rsun from Sun center. The slow wind arises from a region with open field lines and weak anisotropy surrounding the equatorial streamer belt. The model parameters were chosen to reproduce the observed latitudinal extent of the equatorial streamer in the corona and at large distance from the Sun. We find that the magnetic cusp of the closed-field streamer core lies at about 1.95 Rsun. The transition from fast to slow wind is due to a decrease in temperature anisotropy combined with the non-monotonic behavior of the non-radial expansion factor in flow tubes that pass near the streamer cusp. In the slow wind, the plasma beta is of order unity and the critical point lies at about 5 Rsun, well beyond the magnetic cusp. The predicted outflow velocities are consistent with OVI Doppler dimming measurements from UVCS/SOHO. We also find good agreement with polarized brightness (pB) measurements from LASCO/SOHO and HI Ly-alpha images from UVCS/SOHO.Comment: 36 pages, 13 figures. AAS LaTeX Macros v5.0. To appear in The Astrophysical Journal, Vol. 598, No. 2, Issue December 1, 200

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far