Interchange reconnection as the source of the fast solar wind within coronal holes.

The fast solar wind that fills the heliosphere originates from deep within regions of open magnetic field on the Sun called 'coronal holes'. The energy source responsible for accelerating the plasma is widely debated; however, there is evidence that it is ultimately magnetic in nature, with candidate mechanisms including wave heating1,2 and interchange reconnection3-5. The coronal magnetic field near the solar surface is structured on scales associated with 'supergranulation' convection cells, whereby descending flows create intense fields. The energy density in these 'network' magnetic field bundles is a candidate energy source for the wind. Here we report measurements of fast solar wind streams from the Parker Solar Probe (PSP) spacecraft6 that provide strong evidence for the interchange reconnection mechanism. We show that the supergranulation structure at the coronal base remains imprinted in the near-Sun solar wind, resulting in asymmetric patches of magnetic 'switchbacks'7,8 and bursty wind streams with power-law-like energetic ion spectra to beyond 100 keV. Computer simulations of interchange reconnection support key features of the observations, including the ion spectra. Important characteristics of interchange reconnection in the low corona are inferred from the data, including that the reconnection is collisionless and that the energy release rate is sufficient to power the fast wind. In this scenario, magnetic reconnection is continuous and the wind is driven by both the resulting plasma pressure and the radial Alfvénic flow bursts.

Alfvénic velocity spikes and rotational flows in the near-Sun solar wind.

The prediction of a supersonic solar wind1 was first confirmed by spacecraft near Earth2,3 and later by spacecraft at heliocentric distances as small as 62 solar radii4. These missions showed that plasma accelerates as it emerges from the corona, aided by unidentified processes that transport energy outwards from the Sun before depositing it in the wind. Alfvénic fluctuations are a promising candidate for such a process because they are seen in the corona and solar wind and contain considerable energy5-7. Magnetic tension forces the corona to co-rotate with the Sun, but any residual rotation far from the Sun reported until now has been much smaller than the amplitude of waves and deflections from interacting wind streams8. Here we report observations of solar-wind plasma at heliocentric distances of about 35 solar radii9-11, well within the distance at which stream interactions become important. We find that Alfvén waves organize into structured velocity spikes with duration of up to minutes, which are associated with propagating S-like bends in the magnetic-field lines. We detect an increasing rotational component to the flow velocity of the solar wind around the Sun, peaking at 35 to 50 kilometres per second-considerably above the amplitude of the waves. These flows exceed classical velocity predictions of a few kilometres per second, challenging models of circulation in the corona and calling into question our understanding of how stars lose angular momentum and spin down as they age12-14.

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.

A genomic case study of mixed fibrolamellar hepatocellular carcinoma.

BACKGROUND: Mixed fibrolamellar hepatocellular carcinoma (mFL-HCC) is a rare liver tumor defined by the presence of both pure FL-HCC and conventional HCC components, represents up to 25% of cases of FL-HCC, and has been associated with worse prognosis. Recent genomic characterization of pure FL-HCC identified a highly recurrent transcript fusion (DNAJB1:PRKACA) not found in conventional HCC. PATIENTS AND METHODS: We performed exome and transcriptome sequencing of a case of mFL-HCC. A novel BAC-capture approach was developed to identify a 400 kb deletion as the underlying genomic mechanism for a DNAJB1:PRKACA fusion in this case. A sensitive Nanostring Elements assay was used to screen for this transcript fusion in a second case of mFL-HCC, 112 additional HCC samples and 44 adjacent non-tumor liver samples. RESULTS: We report the first comprehensive genomic analysis of a case of mFL-HCC. No common HCC-associated mutations were identified. The very low mutation rate of this case, large number of mostly single-copy, long-range copy number variants, and high expression of ERBB2 were more consistent with previous reports of pure FL-HCC than conventional HCC. In particular, the DNAJB1:PRKACA fusion transcript specifically associated with pure FL-HCC was detected at very high expression levels. Subsequent analysis revealed the presence of this fusion in all primary and metastatic samples, including those with mixed or conventional HCC pathology. A second case of mFL-HCC confirmed our finding that the fusion was detectable in conventional components. An expanded screen identified a third case of fusion-positive HCC, which upon review, also had both conventional and fibrolamellar features. This screen confirmed the absence of the fusion in all conventional HCC and adjacent non-tumor liver samples. CONCLUSION: These results indicate that mFL-HCC is similar to pure FL-HCC at the genomic level and the DNAJB1:PRKACA fusion can be used as a diagnostic tool for both pure and mFL-HCC.

Direct evidence for a three-dimensional magnetic flux rope flanked by two active magnetic reconnection X lines at Earth's magnetopause.

We report the direct detection by three THEMIS spacecraft of a magnetic flux rope flanked by two active X lines producing colliding plasma jets near the center of the flux rope. The observed density depletion and open magnetic field topology inside the flux rope reveal important three-dimensional effects. There was also evidence for nonthermal electron energization within the flux rope core where the fluxes of 1-4 keV superthermal electrons were higher than those in the converging reconnection jets. The observed ion and electron energizations differ from current theoretical predictions.

New features of electron phase space holes observed by the THEMIS mission.

Observations of electron phase-space holes (EHs) in Earth's plasma sheet by the THEMIS satellites include the first detection of a magnetic perturbation (deltaB_{ parallel}) parallel to the ambient magnetic field (B0). EHs with a detectable deltaB_{ parallel} have several distinguishing features including large electric field amplitudes, a magnetic perturbation perpendicular to B0, high speeds ( approximately 0.3c) along B0, and sizes along B0 of tens of Debye lengths. These EHs have a significant center potential (Phi approximately k_{B}T_{e}/e), suggesting strongly nonlinear behavior nearby such as double layers or magnetic reconnection.

Observations of double layers in earth's plasma sheet.

We report the first direct observations of parallel electric fields (E_{ parallel}) carried by double layers (DLs) in the plasma sheet of Earth's magnetosphere. The DL observations, made by the THEMIS spacecraft, have E_{ parallel} signals that are analogous to those reported in the auroral region. DLs are observed during bursty bulk flow events, in the current sheet, and in plasma sheet boundary layer, all during periods of strong magnetic fluctuations. These observations imply that DLs are a universal process and that strongly nonlinear and kinetic behavior is intrinsic to Earth's plasma sheet.

Evidence for electron acceleration up to approximately 300 keV in the magnetic reconnection diffusion region of earth's magnetotail.

We report direct measurements of high-energy particles in a rare crossing of the diffusion region in Earth's magnetotail by the Wind spacecraft. The fluxes of energetic electrons up to approximately 300 keV peak near the center of the diffusion region and decrease monotonically away from this region. The diffusion region electron flux spectrum obeys a power law with an index of -3.8 above approximately 2 keV, and the electron angular distribution displays strong field-aligned bidirectional anisotropy at energies below approximately 2 keV, becoming isotropic above approximately 6 keV. These observations indicate significant electron acceleration inside the diffusion region. Ions show no such energization.

Dexamethasone stimulates ribosomal protein L32 gene transcription in rat myoblasts.

Incubation of rat L6 myoblasts for 24 h with 10(-7) M dexamethasone, a glucocorticoid analogue, resulted in a 2.5-fold increase in the rate of ribosomal protein L32 (rpL32) gene transcription with a corresponding increase in the level of rpL32 mRNA. The increased rate of transcription was accompanied by a dramatic enhancement in binding of the delta, but not beta and gamma, factors to the rpL32 gene promoter as measured by gel mobility shift assays. This increased binding reflects a change in the activity of the delta factor since its level is unchanged by dexamethasone treatment. The presence of the glucocorticoid analogue RU38486 reversed the stimulating effect of dexamethasone on rpL32 gene transcription and binding of the delta factor to the delta element. These results suggest that the mechanism which enhances rpL32 gene transcription in dexamethasone-treated rat L6 myoblasts involves glucocorticoid-receptor mediated changes in the activity of the delta factor.

Energy expenditure and free-living physical activity in black and white women: comparison before and after weight loss.

BACKGROUND: The prevalence of obesity is higher in black than in white women. Differences in energy economy and physical activity may contribute to this difference. OBJECTIVE: The objective of this study was to compare free-living energy expenditure and physical activity in black and white women before and after weight loss. DESIGN: Participants were 18 white and 14 black women with body mass indexes (in kg/m(2)) between 27 and 30. Diet, without exercise, was used to achieve a weight loss of >/=10 kg and a body mass index <25. After 4 wk of energy balance in overweight and normal-weight states, body composition was assessed by using a 4-compartment model, sleeping and resting energy expenditures were assessed by using a chamber calorimeter, physiologic stress of exercise and exercise economy were measured by using standardized exercise tasks, and daily energy expenditure was assessed by using doubly labeled water. RESULTS: Weight loss averaged 12.8 kg. Sleeping and resting energy expenditures decreased in proportion to changes in body composition. Weight reduction significantly improved physiologic capacity for exercise in both groups of women, making it easier for them to be physically active. Black women had lower body composition-adjusted energy requirements than did white women-both before and after weight loss-during sleep (9% lower, 519 kJ/d; P < 0.001), at rest (14% lower, 879 kJ/d; P < 0.001), during exercise (6% lower; P < 0. 05), and as a daily total (9% lower, 862 kJ/d; P < 0.06). By contrast, free-living physical activity was similar between the groups. CONCLUSIONS: Weight-reduced women had metabolic rates appropriate for their body sizes. Black women had lower resting and nonresting energy requirements in both overweight and normal-weight states than did white women and did not compensate with greater physical activity, potentially predisposing them to greater weight regain.

A role for high intensity exercise on energy balance and weight control.

The objective of this commentary is to remark on the impact, exercise intensity has on energy expenditure and its potential for body weight control. Exercise intensity can favorably impact on energy expenditure in a number of ways. First, exercise-associated energy expenditure is increased by decreasing exercise efficiency and increasing work rate. Second, resistance training that increases muscle mass, in turn increases resting energy expenditure. Third, aerobic exercise > 70% VO2max, increases resting energy expenditure separate from any change in muscle mass. High-intensity exercise training has the added benefit of improving fitness, thus making low-intensity exercise less difficult and more easily tolerated. Although continuous intense exercise is difficult to maintain for extended periods of time, intense interval exercise can be easily endured and may be an important adjunct to lifestyle modifications for body weight control.

Topology of recombinant rat upstream binding factor.

Transmission electron microscopy and single particle electron crystallography were employed to reconstruct high-quality projection images of a recombinant, acidic tail deficient form of rat upstream binding factor. The upstream binding factor was found to be dimeric and approximately 10 nm in diameter with a central region of low density. Distinct nodes were observable, of size and spacing consistent with being HMG boxes 3 and 4. The dimerisation domain seemed most probably to be located in the internal region of the structure.

GA-binding protein is involved in altered expression of ribosomal protein L32 gene.

Differentiation of BC3H1 myoblasts to myocytes is accompanied by a 67% drop in the rate of rpL32 gene transcription. Addition of high concentrations of serum to resting myocyte populations stimulates cell growth and subsequent dedifferentiation to proliferating myoblasts with a return to the normal rate of rpL32 gene transcription. During these growth rate changes the binding activities of previously identified factors (beta, gamma, delta) which interact with the rpL32 gene promoter were examined by mobility shift assays. Binding of the beta factor (an Ets related protein) to an oligonucleotide containing the beta element was reduced significantly in myocyte nuclear extracts, but subsequent dedifferentiation increased binding within 30 min in either the presence or absence of the cycloheximide. Binding of the gamma and delta factors to their respective elements changed only slightly during these processes. Dephosphorylation of either myoblast or myocyte extracts resulted in increased binding of the beta factor suggesting that binding activity of the beta factor is modulated by phosphorylation during the changes in BC3H1 myoblasts growth rate. In addition, mobility shift assays with recombinant GABP alpha and beta proteins and their specific antibodies revealed that GABP proteins bind to the rpL32 gene promoter in a sequence dependent manner, and that similar proteins are present in BC3H1 myoblast/myocyte extracts. These results support the premise that the GABP heterodimer is the rpL32 beta factor. Furthermore, during BC3H1 myoblast differentiation and dedifferentiation neither the levels of the GABP alpha and beta proteins nor their respective mRNAs change. These results suggest that GABP is a constitutively expressed protein and is involved in regulating rpL32 gene by post-transcriptional modifications.

Ad libitum food intake in humans after manipulation of glycogen stores.

It is controversial whether food intake in humans is under day-to-day regulation to maintain constant body glycogen stores. In eight white males with a mean (+/-SD) age of 30 +/- 4 y, body weight of 82 +/- 20 kg, and percentage body fat of 22 +/- 5%, exercise and diets were used to produce either high (HG) or low glycogen (LG) stores in a randomized crossover design. After each treatment a vastus lateralis muscle biopsy was obtained. Subsequent ad libitum food intake was measured with an automated food-selection system during 2 d in a respiratory chamber. Despite a 46 +/- 21% difference in muscle glycogen between the two treatments, ad libitum 2-d food intakes (energy, weight, or macronutrients) were similar between treatments (HG: 23.80 +/- 4.67 MJ/d; LG: 21.20 +/- 6.73 MJ/d). However, energy intake on the second day of ad libitum feeding was negatively correlated with carbohydrate balance on the first day, adjusted for the effect of total energy intake and treatment. Adjusted carbohydrate balance on day 1 only explained 9% of the variance in energy intake on day 2. The 24-h respiratory quotient on the first day after treatment was higher after the HG than after the LG treatment: 0.94 +/- 0.04 and 0.88 +/- 0.07 (P < 0.001). The findings suggest that 1) body glycogen stores play at most a minor role in short-term food intake regulation, and 2) in the short term, imbalances in glycogen stores are corrected by adjustments of macronutrient oxidation rates.

Cross-validation of prediction equations for resting energy expenditure in young, healthy children.

OBJECTIVE: To examine the accuracy of several prediction equations for resting energy expenditure (REE) in children. DESIGN: REE was measured in 113 prepubertal children (60 girls and 53 boys aged 3.9 to 7.8 years old, weighing 14.7 to 30.0 kg) using indirect calorimetry and compared with values estimated from the prediction equations of Altman and Dittmer, The Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU), Maffeis et al, and Harris and Benedict. STATISTICAL ANALYSIS: Measured REE (MREE) was compared with predicted REE (PREE) by means of regression analysis. Prediction equations were considered accurate if the regression of MREE vs PREE was not significantly different from the line of identity (slope=1.0; intercept=0). Precision was assessed by the multiple correlation coefficient of the regression of MREE vs PREE. RESULTS: MREE was 938+/-119 kcal/day, and PREE was 1,057+/-224 kcal/day for the Altman and Dittmer equations, 956+/-84 kcal/day for the FAO/WHO/UNU equations, 948+/-64 kcal/day for the equations of Maffeis et al, and 954+/-102 kcal/day for the Harris-Benedict equations. The regression of MREE vs PREE was significantly different from the line of identity for all prediction equations except the FAO/WHO/UNU equations (slope=0.96, P=.735; intercept=-15 kcal/day, P=.885 for girls and slope=1.08, P=.635; intercept=-62 kcal/day, P=.635 for boys). None of the equations was precise for MREE vs PREE (for all, R2<.6). For the FAO/WHO/UNU equations, less than half of the predictions were within +/-50 kcal/day but 99% were within 200 kcal/day. CONCLUSION: Most prediction equations for REE in children do not accurately or precisely estimate REEs. The exception is the FAO/WHO/UNU equations, which are reasonably accurate and precise for practical purposes.

Dietary fat in relation to body fat and intraabdominal adipose tissue: a cross-sectional analysis.

Numerous studies report positive links between dietary fat and adiposity. However, the relation between fat intake and intraabdominal adipose tissue (IAAT), a risk factor for cardiovascular disease and diabetes, is not known. We therefore evaluated the association between dietary fat and adipose tissue stores in 135 white men aged 44 +/- 10 y (mean+/- SD: weight, 86 +/- 14 kg; body fat, 23 +/- 8%) and in 214 white women aged 45 +/- 14 y (weight, 64 +/- 12 kg; body fat, 33 +/- 10%). Dietary intake was estimated from 3-d food records, body composition from hydrostatic weighing, IAAT and subcutaneous abdominal adipose tissue (SCAAT) by computed tomography, and physical activity by using the Baecke Questionnaire. After adjustment for fat-free mass, sex, age, physical activity, and nonfat energy intake, fat intake was weakly correlated with fat mass, explaining only 2% of the variance (partial R2 = 0.018, P < 0.01). In a separate model that evaluated type of fat, saturated fat was positively related (partial R2 = 0.025, P < 0.01) to fat mass after adjustment for fat-free mass, sex, age, physical activity, and nonfat energy intake whereas polyunsaturated fat intake was negatively related (partial R2 = 0.007, P = 0.056). On the basis of partial correlation analyses, dietary fat was also associated with SCAAT adjusted for nonfat energy intake and IAAT (partial R2 = 0.014, P < 0.01), but not IAAT adjusted for nonfat energy intake and SCAAT. However, the association between dietary fat and adjusted SCAAT was not significant after further adjustment for sex, age, and physical activity. Thus, results of this cross-sectional analysis suggest that dietary fat independently plays a very minor role in increasing overall adiposity and does not specifically influence fat accretion in the intraabdominal region.

Effects of glucocorticoids on energy metabolism and food intake in humans.

The effect of glucocorticoid administration on energy metabolism and food intake was studied in 20 healthy, nondiabetic Caucasian male volunteers [27 +/- 5 (SD) yr, 72 +/- 9 kg, 20 +/- 7% body fat] randomly and blindly assigned to glucocorticoid (methylprednisolone, METH; n = 10) or placebo (PLAC; n = 10) treatment. Each subject was studied twice: during a weight maintenance diet and during ad libitum food intake. Energy metabolism was measured by indirect calorimetry and food intake by an automated food-selection system. Twenty-four-hour urinary norepinephrine excretion (24-h NE) was used as an estimate of sympathetic nervous system activity. During weight maintenance, METH intravenous infusion (125 mg/30 min) increased energy expenditure compared with PLAC, and after 4 days of oral therapy, METH (40 mg/day) decreased 24-h NE and increased energy expenditure compared with PLAC. During ad libitum food intake, after 4 days of METH (40 mg/day) or PLAC oral therapy, both groups increased their energy intake over weight maintenance, but the increase was significantly larger in the METH group compared with the PLAC group (4,554 +/- 1,857 vs. 2,867 +/- 846 kcal/day; P = 0.04). Our data suggest that therapeutic doses of glucocorticoids induce obesity mostly by increasing energy intake, an effect which may be related to the ability of glucocorticoids to act directly or indirectly on the central regulation of appetite.

Altered subcellular distribution of U3 snRNA in response to serum in mouse fibroblasts.

To extend our understanding of the mechanisms regulating ribosome biosynthesis during changes in cellular growth rate, the expression and subcellular distribution of U3 snRNA and one of its associated proteins, fibrillarin, were examined in mouse 3T6 fibroblasts. Altering serum concentrations produces changes in the ribosome content of the cell as reflected by total RNA levels. When exponentially growing 3T6 cells are induced to become quiescent by serum starvation, a significant downshift in U3 snRNA gene transcription occurs in parallel to a decrease in pre-rRNA synthesis. Serum stimulation results in an increase in the rate of synthesis of both U3 snRNA and pre-rRNA. However, U3 snRNA synthesis lags behind that of pre-rRNA. Furthermore, in serum-starved fibroblasts, a significant portion of the total cellular U3 snRNA appears in the cytoplasm. Following serum stimulation, a redistribution occurs and U3 snRNA is localized predominantly in the nucleolus at a level similar to that observed in exponentially growing cells. This redistribution is inhibited when RNA or protein synthesis is repressed in serum-stimulated fibroblasts by actinomycin D or cycloheximide. In contrast, the level and subcellular distribution of fibrillarin remain unchanged during serum starvation. These results suggest that during changes in ribosome production, distinct pools of U3 snRNPs exist within the cell.

Fat intake and adiposity in children of lean and obese parents.

We examined the relations between obesity in parents and fat intake in their children, and the effect of fat intake on fat mass in these children. Our heterogenous sample (-x+/-SD: 20.2+/-3.4 kg; 3.2+/-1.3kg fat mass) consisted of 56 white and 15 Mohawk children 4-7 y of age (35 girls and 36 boys). Dietary intake was assessed with the Willett food-frequency questionnaire revised for children. Body composition was measured by bioelectrical resistance and subscapular and triceps skinfold thicknesses. Physical-activity energy expenditure was estimated by the difference between total energy expenditure (measured over 14 d by the doubly labeled water method) and postprandial resting energy expenditure (measured by indirect calorimetry). Before statistical analysis, fat mass was adjusted for fat-free mass, and fat intake was adjusted for nonfat intake. There was no effect of sex or ethnicity on fat intake and no effect of ethnicity on the relation between fat intake and fat mass. Adjusted mean (+/-SE) fat intakes for the groups of children, based on parental obesity status, were as follows: 1.65+/-0.09 MJ/d (nonobese mother and father), 2.58+/-0.10 MJ/d (obese father, nonobese mother), and 2.79+/-0.10 MJ/d (obese mother and father). We found an influence of maternal obesity on dietary fat intake in children (P=0.052) and a significant correlation between fat mass and fat intake in boys (r=0.48, P<0.01) but not in girls after adjustment for physical-activity energy expenditure. Our data suggest that 1)mothers may contribute to the development of obesity in children by influencing their dietary fat intake, and 2) dietary fat intake contributes to obesity in boys, independent of physical-activity energy expenditure.