Highly structured slow solar wind emerging from an equatorial coronal hole.

During the solar minimum, when the Sun is at its least active, the solar wind1,2 is observed at high latitudes as a predominantly fast (more than 500 kilometres per second), highly Alfvénic rarefied stream of plasma originating from deep within coronal holes. Closer to the ecliptic plane, the solar wind is interspersed with a more variable slow wind3 of less than 500 kilometres per second. The precise origins of the slow wind streams are less certain4; theories and observations suggest that they may originate at the tips of helmet streamers5,6, from interchange reconnection near coronal hole boundaries7,8, or within coronal holes with highly diverging magnetic fields9,10. The heating mechanism required to drive the solar wind is also unresolved, although candidate mechanisms include Alfvén-wave turbulence11,12, heating by reconnection in nanoflares13, ion cyclotron wave heating14 and acceleration by thermal gradients1. At a distance of one astronomical unit, the wind is mixed and evolved, and therefore much of the diagnostic structure of these sources and processes has been lost. Here we present observations from the Parker Solar Probe15 at 36 to 54 solar radii that show evidence of slow Alfvénic solar wind emerging from a small equatorial coronal hole. The measured magnetic field exhibits patches of large, intermittent reversals that are associated with jets of plasma and enhanced Poynting flux and that are interspersed in a smoother and less turbulent flow with a near-radial magnetic field. Furthermore, plasma-wave measurements suggest the existence of electron and ion velocity-space micro-instabilities10,16 that are associated with plasma heating and thermalization processes. Our measurements suggest that there is an impulsive mechanism associated with solar-wind energization and that micro-instabilities play a part in heating, and we provide evidence that low-latitude coronal holes are a key source of the slow solar wind.

Explosive Particle Dispersion in Plasma Turbulence.

Particle dynamics are investigated in plasma turbulence, using self-consistent kinetic simulations, in two dimensions. In the steady state, the trajectories of single protons and proton pairs are studied, at different values of plasma ß (ratio between kinetic and magnetic pressure). For single-particle displacements, results are consistent with fluids and magnetic field line dynamics, where particles undergo normal diffusion for very long times, with higher ß's being more diffusive. In an intermediate time range, with separations lying in the inertial range, particles experience an explosive dispersion in time, consistent with the Richardson prediction. These results, obtained for the first time with a self-consistent kinetic model, are relevant for astrophysical and laboratory plasmas, where turbulence is crucial for heating, mixing, and acceleration processes.

Quasiperpendicular High Mach Number Shocks.

Shock waves exist throughout the Universe and are fundamental to understanding the nature of collisionless plasmas. Reformation is a process, driven by microphysics, which typically occurs at high Mach number supercritical shocks. While ongoing studies have investigated this process extensively both theoretically and via simulations, their observations remain few and far between. In this Letter we present a study of very high Mach number shocks in a parameter space that has been poorly explored and we identify reformation using in situ magnetic field observations from the Cassini spacecraft at 10 AU. This has given us an insight into quasiperpendicular shocks across 2 orders of magnitude in Alfvén Mach number (M_{A}) which could potentially bridge the gap between modest terrestrial shocks and more exotic astrophysical shocks. For the first time, we show evidence for cyclic reformation controlled by specular ion reflection occurring at the predicted time scale of ~0.3τ_{c}, where τ_{c} is the ion gyroperiod. In addition, we experimentally reveal the relationship between reformation and M_{A} and focus on the magnetic structure of such shocks to further show that for the same M_{A}, a reforming shock exhibits stronger magnetic field amplification than a shock that is not reforming.

Home-made explosive found inside injured Afghan.

There is extensive literature on metal fragments from improvised explosive devices being embedded in patients but there are no reports describing the clinical and radiological appearances of embedded home-made explosive (HME). We present a case of partially detonated HME being found inside a patient's forearm. We discuss the medical management of the injury, the ongoing risk to the patient and surgical team associated with the explosive and the safe disposal of the substance.

Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'.

The mouse neurological mutant 'motor endplate disease' (med) is characterized by early onset progressive paralysis of the hind limbs, severe muscle atrophy, degeneration of Purkinje cells and juvenile lethality. We have isolated a voltage-gated sodium channel gene, Scn8a, from the flanking region of a transgene-induced allele of med. Scn8a is expressed in brain and spinal cord but not in skeletal muscle or heart, and encodes a predicted protein of 1,732 amino acids. An intragenic deletion at the transgene insertion site results in loss of expression. Scn8a is closely related to other sodium channel alpha subunits, with greatest similarity to a brain transcript from the pufferfish Fugu rubripes. The human homologue, SCN8A, maps to chromosome 12q13 and is a candidate gene for inherited neurodegenerative disease.

Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10.

Spinocerebellar ataxia type 10 (SCA10; MIM 603516; refs 1,2) is an autosomal dominant disorder characterized by cerebellar ataxia and seizures. The gene SCA10 maps to a 3.8-cM interval on human chromosome 22q13-qter (refs 1,2). Because several other SCA subtypes show trinucleotide repeat expansions, we examined microsatellites in this region. We found an expansion of a pentanucleotide (ATTCT) repeat in intron 9 of SCA10 in all patients in five Mexican SCA10 families. There was an inverse correlation between the expansion size, up to 22.5 kb larger than the normal allele, and the age of onset (r2=0.34, P=0.018). Analysis of 562 chromosomes from unaffected individuals of various ethnic origins (including 242 chromosomes from Mexican persons) showed a range of 10 to 22 ATTCT repeats with no evidence of expansions. Our data indicate that the new SCA10 intronic ATTCT pentanucleotide repeat in SCA10 patients is unstable and represents the largest microsatellite expansion found so far in the human genome.

Gender differences in PTSD severity and pain outcomes: baseline results from the LAMP trial.

Background: Post-traumatic stress disorder (PTSD) and chronic pain are highly prevalent comorbid conditions. Veterans dually burdened by PTSD and chronic pain experience more severe outcomes compared to either disorder alone. Few studies have enrolled enough women Veterans to test gender differences in pain outcomes [catastrophizing, intensity, interference] by the severity of PTSD. Aim: Examine gender differences in the association between PTSD symptoms and pain outcomes among Veterans enrolled in a chronic pain clinical trial. Methods: Participants were 421 men and 386 women Veterans with chronic pain who provided complete data on PTSD symptoms and pain outcomes. We used hierarchical linear regression models to examine gender differences in pain outcomes by PTSD symptoms. Results: Adjusted multivariable models indicated that PTSD symptoms were associated with higher levels of pain catastrophizing (0.57, 95% CI [0.51, 0.63]), pain intensity (0.30, 95% CI [0.24, 0.37]), and pain interference (0.46, 95% CI [0.39, 0.52]). No evidence suggesting differences in this association were found in either the crude or adjusted models (all interaction p-values<0.05). Conclusion: These findings may reflect the underlying mutual maintenance of these conditions whereby the sensation of pain could trigger PTSD symptoms, particularly if the trauma and pain are associated with the same event. Clinical implications and opportunities testing relevant treatments that may benefit both chronic pain and PTSD are discussed.

Microsphere erosion in outer hydrogel membranes creating macroscopic porosity to counter biofouling-induced sensor degradation.

Biofouling and tissue inflammation present major challenges toward the realization of long-term implantable glucose sensors. Following sensor implantation, proteins and cells adsorb on sensor surfaces to not only inhibit glucose flux but also signal a cascade of inflammatory events that eventually lead to permeability-reducing fibrotic encapsulation. The use of drug-eluting hydrogels as outer sensor coatings has shown considerable promise to mitigate these problems via the localized delivery of tissue response modifiers to suppress inflammation and fibrosis, along with reducing protein and cell absorption. Biodegradable poly (lactic-co-glycolic) acid (PLGA) microspheres, encapsulated within a poly (vinyl alcohol) (PVA) hydrogel matrix, present a model coating where the localized delivery of the potent anti-inflammatory drug dexamethasone has been shown to suppress inflammation over a period of 1-3 months. Here, it is shown that the degradation of the PLGA microspheres provides an auxiliary venue to offset the negative effects of protein adsorption. This was realized by: (1) the creation of fresh porosity within the PVA hydrogel following microsphere degradation (which is sustained until the complete microsphere degradation) and (2) rigidification of the PVA hydrogel to prevent its complete collapse onto the newly created void space. Incubation of the coated sensors in phosphate buffered saline (PBS) led to a monotonic increase in glucose permeability (50%), with a corresponding enhancement in sensor sensitivity over a 1 month period. Incubation in serum resulted in biofouling and consequent clogging of the hydrogel microporosity. This, however, was partially offset by the generated macroscopic porosity following microsphere degradation. As a result of this, a 2-fold recovery in sensor sensitivity for devices with microsphere/hydrogel composite coatings was observed as opposed to similar devices with blank hydrogel coatings. These findings suggest that the use of macroscopic porosity can reduce sensitivity drifts resulting from biofouling, and this can be achieved synergistically with current efforts to mitigate negative tissue responses through localized and sustained drug delivery.

A Kinetic Mechanism for CF3I Inhibition of Methane-Air Flames.

The influence of CF3I on the burning velocity of methane-air flame is experimentally and numerically studied. Experimental results demonstrate that the inhibition effectiveness of CF3I is very close to that of CF3Br. A detailed kinetic model of flame inhibition by CF3I is presented, based on an updated version of a previous model. The kinetic model contains 1072 reactions with 115 species including 10 iodine-containing species. Modeling results demonstrate good agreement with experimental data, and both experiments and calculations show that CF3I is only slightly less effective at reducing the burning velocity than CF3Br. The flame structure predicted from numerical simulations is analyzed and shows that main reactions of the inhibition cycle of CF3I are: H+HI=H2+I; H+I+M=HI+M; I+I+M=I2+M; H+I2=HI+I; I+CH3+M=CH3I+M; H+CH3I=CH3+HI; I+HCO=HI+CO; HI+OH=H2O+I and O+HI=I+OH.

The congested International Match Calendar in football: views of 1055 professional male players.

BACKGROUND: The International Match Calendar congestion affects players recovery. The views of a worldwide cohort of professional football players is shared in this communication. METHODS: A cross-sectional observational study recruited players through Fédération Internationale des Associations de Footballeurs Professionnel's national members. An electronic survey was shared in English, French, Italian and Spanish with 1055 players consenting and completing it anonymously in November 2021. RESULTS: A total of 42% of respondents believe back-to-back matches should be limited to three. Most respondents (69%) felt off or in season breaks are infringed by clubs or national teams and 83% believe regulations should protect them. A total of 55% of players believed they sustained one or more injuries due to the overload and it has affected 52% of respondents' mental state. CONCLUSION: The congested International Match Calendar poses a risk to professional footballers physical and mental health. Poor recovery between matches may affect player availability and performance. Players should be represented by active players when International Match Calendar scheduling decisions are made. Administrators should seek medical guidance regarding the effects of overload on performance prior to making decisions. This study allows the opportunity for a larger national team player sample to be studied.

Membrane motility mediated by unconventional myosin.

Largely on the basis of their physical properties and their localization to cell membranes, it has been proposed that the unconventional myosins are membrane motors. In the past year, a combination of immunological, biochemical and genetic approaches has begun to provide direct evidence that unconventional myosins have important roles in movements of the plasma membrane and cytoplasmic organelles.

Glutamate levels in the medial prefrontal cortex of healthy pregnant women compared to non-pregnant controls.

Very little is known about maternal cerebral changes during pregnancy. Since there is an increased risk for major depression during pregnancy and postpartum, it is important to understand the structural and neurochemical changes that occur in the brain during pregnancy. Using proton magnetic resonance spectroscopy (1H-MRS) (3 T field strength), glutamate (Glu) levels were measured in the medial prefrontal cortex (MPFC) of 21 healthy gravid subjects 2-3 weeks before their due date (6.74 ± 1.39), and in 14 non-pregnant healthy controls during their follicular phase (8.53 ± 1.55). Water quantified MPFC Glu levels were decreased in pregnant women (p < 0.01). We also observed a 13.9% decrease in percentage grey matter (%GM) (p < 0.01) in our MPFC voxel. As Glu is mostly found in GM, we repeated the statistical analysis after adjustment for %GM and found that the difference in Glu levels was no longer statistically significant when adjusted for %GM (p = 0.10). This investigation is the only systematic direct investigation of brain tissue composition and Glu levels in pregnant women. The main finding of this investigation is the decreased %GM in healthy pregnant women compared to non-pregnant women. These findings of decreased %GM in pregnancy may be responsible for the frequent complaints by pregnant women of cognitive difficulties also described as pregnesia.

Human monocytes can produce tissue-type plasminogen activator.

Evidence has previously been presented that monocytes and macrophages produce urokinase-type plasminogen activator. We have shown for the first time that human monocytes, when stimulated appropriately in vitro, can produce tissue type-plasminogen activator (t-PA) of 70 kD. Detection of t-PA mRNA was consistent with the biochemical and immunological characterization of t-PA produced by human monocytes.

Budding roles for myosin II on the Golgi.

Myosin II--conventional myosin--has been typecast in muscle-man roles. While members of the Schwarzenegger clan from skeletal muscle have grabbed the limelight, myosin II motors in nonmuscle cells labour away in many varied and subtle roles. Recent findings show that nonmuscle myosin II, along with other myosins and cytoskeletal proteins, assembles on Golgi membranes. Nonmuscle myosin II associates transiently with membranes of the trans-Golgi network during the budding of a subpopulation of transport vesicles. The exact role of myosin II in vesicular trafficking is not yet understood, but its participation heralds a novel role for actin-based motors in vesicle budding.

Reactivation of intestinal epithelial cell brush border motility: ATP-dependent contraction via a terminal web contractile ring.

Various models have been put forward suggesting ways in which brush borders from intestinal epithelial cells may be motile. Experiments documenting putative brush border motility have been performed on isolated brush borders and have generated models suggesting microvillar retraction or microvillar rootlet interactions. The reported Ca++ ATP-induced retraction of microvilli has been shown, instead, to be microvillar dissolution in response to Ca++ and not active brush border motility. I report here studies on the reactivation of motility in intact sheets of isolated intestinal epithelium. Whole epithelial sheets were glycerinated, which leaves the brush border and intercellular junctions intact, and then treated with ATP, PPi, ITP, ADP, GTP, or delta S-ATP. Analysis by video enhanced differential interference-contrast microscopy and thin-section transmission electron microscopy reveals contractions in the terminal web region causing microvilli to be fanned apart in response to ATP and delta S-ATP but not in response to ADP, PPi, ITP, or GTP. Electron microscopy reveals that the contractions occur at the level of the intermediate junction in a circumferential constriction which can pull cells completely apart. This constriction occurs in a location occupied by an actin-containing circumferential band of filaments, as demonstrated by S-1 binding, which completely encircles the terminal web at the level of the intermediate junction. Upon contraction, this band becomes denser and thicker. Since myosin, alpha-actinin and tropomyosin, in addition to actin, have been localized to this region of the terminal web, it is proposed that the intestinal epithelial cell can be motile via a circumferential terminal web contractile ring analogous to the contractile ring of dividing cells.

Low ionic strength solubility of myosin in sea urchin egg extracts is mediated by a myosin-binding protein.

We identify a novel myosin-binding protein, designated 53K, which appears to mediate the low ionic strength solubility of myosin in extracts of unfertilized sea urchin eggs. The protein possesses a subunit molecular mass on SDS-PAGE of 53 kD, an S value of 7, may be organized into disulfide-linked oligomers, and is associated with myosin in egg extracts. Both myosin and 53K co-precipitate from extract upon the addition of nucleoside triphosphates and co-sediment with an S value of 24 by sedimentation velocity centrifugation. Myosin in extracts not associated with 53K has an S value of 10. Further, myosin can be immunoprecipitated from extract with antibody to 53K and the 53K in extracts binds to a myosin affinity column. When extract is depleted of 53K, a majority of the myosin precipitates out of extract in a nucleotide-independent manner. Whereas purified myosin precipitates in the absence of nucleotide when recombined with dialysis buffer or myosin-depleted extract, reconstituting 53K and myosin before addition to buffer or myosin-depleted extract partially restores the low ionic strength solubility demonstrated by myosin in fresh egg extracts. The 53-kD protein may represent a new class of authentic myosin-binding proteins that may regulate the supramolecular organization of myosin in nonmuscle cells.

The brush border cytoskeleton is not static: in vivo turnover of proteins.

The shape and stability of intestinal epithelial cell microvilli are maintained by a cytoskeletal core composed of a bundle of actin filaments with several associated proteins. The core filaments are intimately associated with the overlying plasma membrane, in which there occur rapid turnover of proteins and constant incorporation of new membrane. Previous work has shown that starvation or inhibition of protein synthesis results in modulation of microvillar length, which indicates that there may be cytoskeletal protein turnover. We demonstrate herein, by means of in vivo pulse labeling with radioactive amino acids, that turnover of brush border cytoskeletal proteins occurs in mature absorptive cells. Turnover of cytoskeletal proteins appears to be quite slow relative to membrane protein turnover, which suggests that the turnover of these two microvillar compartments is not coupled. We thus conclude that cytoskeletal protein turnover may be a factor used to maintain normal length and stability of microvilli and that the cytoskeleton cannot be considered a static structure.

Partial reconstruction of the microvillus core bundle: characterization of villin as a Ca++-dependent, actin-bundling/depolymerizing protein.

The brush border, isolated from chicken intestine epithelial cells, contains the 95,000 relative molecular mass (M(r)) polypeptide, villin. This report describes the purification and characterization of villin as a Ca(++)-dependent, actin bundling/depolymerizing protein. Then 100,000 g supernatant from a Ca(++) extract of isolated brush borders is composed of three polypeptides of 95,000 (villin), 68,000 (fimbrin), and 42,000 M(r) (actin). Villin, following purification from this extract by differential ammonium sulfate precipitation and ion-exchange chromatography, was mixed with skeletal muscle F-actin. Electron microscopy of negatively stained preparations of these villin-actin mixtures showed that filament bundles were present. This viscosity, sedimentability, and ultrastructural morphology of filament bundles are dependent on the villin:actin molar ratio, the pH, and the free Ca(++) concentration in solution. At low free Ca(++) (less than 10(-6) M), the amount of protein in bundles, when measured by sedimentation, increased as the villin: actin molar ratio increased and reached a plateau at approximately a 4:10 ratio. This behavior correlates with the conversion of single actin filaments into filament bundles as detected in the electron microscope. At high free Ca(++) (more than 10(-6) M), there was a decrease in the apparent viscosity in the villin-actin mixtures to a level measured for the buffer. Furthermore, these Ca(++) effects were correlated with the loss of protein sedimented, the disappearance of filament bundles, and the appearance of short fragments of filaments. Bundle formation is also pH-sensitive, being favored at mildly acidic pH. A decrease in the pH from 7.6 to 6.6 results in an increase in sedimentable protein and also a transformation of loosly associated actin filaments into compact actin bundles. These results are consistent with the suggestions that villin is a bundling protein in the microvillus and is responsible for the Ca(++)-sensitive disassembly of the microvillar cytoskeleton. Thus villin may function in the cytoplasm as a major cytoskeletal element regulating microvillar shape.

Golgi-derived vesicles from developing epithelial cells bind actin filaments and possess myosin-I as a cytoplasmically oriented peripheral membrane protein.

In the intestinal brush border, the mechanoenzyme myosin-I links the microvillus core actin filaments with the plasma membrane. Previous immunolocalization shows that myosin-I is associated with vesicles in mature enterocytes (Drenckhahn, D., and R. Dermietzel. 1988. J. Cell Biol. 107:1037-1048) suggesting a potential role mediating vesicle motility. We now report that myosin-I is associated with Golgi-derived vesicles isolated from cells that are rapidly assembling brush borders in intestinal crypts. Crypt cells were isolated in hyperosmotic buffer, homogenized, and fractionated using differential- and equilibrium-density centrifugation. Fractions containing 50-100-nm vesicles, a similar size to those observed in situ, were identified by EM and were shown to contain myosin-I as demonstrated by immunoblotting and immunolabel negative staining. Galactosyltransferase, a marker enzyme for trans-Golgi membranes was present in these fractions, as was alkaline phosphatase, which is an apical membrane targeted enzyme. Galactosyltransferase was also present in vesicles immuno-purified with antibodies to myosin-I. Villin, a marker for potential contamination from fragmented microvilli, was absent. Myosin-I was found to reside on the vesicle "outer" or cytoplasmic surface for it was accessible to exogenous proteases and intact vesicles could be immunolabeled with myosin-I antibodies in solution. The bound myosin-I could be extracted from the vesicles using NaCl, KI and Na2CO3, suggesting that it is a vesicle peripheral membrane protein. These vesicles were shown to bundle actin filaments in an ATP-dependent manner. These results are consistent with a role for myosin-I as an apically targeted motor for vesicle translocation in epithelial cells.