Magneto-thermal convection in solar prominences

Coronal cavities are large low-density regions formed by hemispheric-scale magnetic flux ropes suspended in the Sun's outer atmosphere. They evolve over time, eventually erupting as the dark cores of coronal mass ejections. Although coronal mass ejections are common and can significantly affect planetary magnetospheres, the mechanisms by which cavities evolve to an eruptive state remain poorly understood. Recent optical observations of high-latitude 'polar crown' prominences within coronal cavities reveal dark, low-density 'bubbles' that undergo Rayleigh-Taylor instabilities to form dark plumes rising into overlying coronal cavities. These observations offered a possible mechanism for coronal cavity evolution, although the nature of the bubbles, particularly their buoyancy, was hitherto unclear. Here we report simultaneous optical and extreme-ultraviolet observations of polar crown prominences that show that these bubbles contain plasma at temperatures in the range (2.5-12)?×?10(5) kelvin, which is 25-120 times hotter than the overlying prominence. This identifies a source of the buoyancy, and suggests that the coronal cavity-prominence system supports a novel form of magneto-thermal convection in the solar atmosphere, challenging current hydromagnetic concepts of prominences and their relation to coronal cavities.     

Regulation of p53 activity through lysine methylation

p53 is a tumour suppressor that regulates the cellular response to genotoxic stresses. p53 is a short-lived protein and its activity is regulated mostly by stabilization via different post-translational modifications. Here we report a novel mechanism of p53 regulation through lysine methylation by Set9 methyltransferase. Set9 specifically methylates p53 at one residue within the carboxyl-terminus regulatory region. Methylated p53 is restricted to the nucleus and the modification positively affects its stability. Set9 regulates the expression of p53 target genes in a manner dependent on the p53-methylation site. The crystal structure of a ternary complex of Set9 with a p53 peptide and the cofactor product S-adenosyl-l-homocysteine (AdoHcy) provides the molecular basis for recognition of p53 by this lysine methyltransferase.     

Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by features reminiscent of marked premature ageing. Here, we present evidence of mutations in lamin A (LMNA) as the cause of this disorder. The HGPS gene was initially localized to chromosome 1q by observing two cases of uniparental isodisomy of 1q-the inheritance of both copies of this material from one parent-and one case with a 6-megabase paternal interstitial deletion. Sequencing of LMNA, located in this interval and previously implicated in several other heritable disorders, revealed that 18 out of 20 classical cases of HGPS harboured an identical de novo (that is, newly arisen and not inherited) single-base substitution, G608G(GGC > GGT), within exon 11. One additional case was identified with a different substitution within the same codon. Both of these mutations result in activation of a cryptic splice site within exon 11, resulting in production of a protein product that deletes 50 amino acids near the carboxy terminus. Immunofluorescence of HGPS fibroblasts with antibodies directed against lamin A revealed that many cells show visible abnormalities of the nuclear membrane. The discovery of the molecular basis of this disease may shed light on the general phenomenon of human ageing.     

Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase

Mycobacterium tuberculosis claims more human lives each year than any other bacterial pathogen. Infection is maintained in spite of acquired immunity and resists eradication by antimicrobials. Despite an urgent need for new therapies targeting persistent bacteria, our knowledge of bacterial metabolism throughout the course of infection remains rudimentary. Here we report that persistence of M. tuberculosis in mice is facilitated by isocitrate lyase (ICL), an enzyme essential for the metabolism of fatty acids. Disruption of the icl gene attenuated bacterial persistence and virulence in immune-competent mice without affecting bacterial growth during the acute phase of infection. A link between the requirement for ICL and the immune status of the host was established by the restored virulence of delta icl bacteria in interferon-gamma knockout mice. This link was apparent at the level of the infected macrophage: Activation of infected macrophages increased expression of ICL, and the delta icl mutant was markedly attenuated for survival in activated but not resting macrophages. These data suggest that the metabolism of M. tuberculosis in vivo is profoundly influenced by the host response to infection, an observation with important implications for the treatment of chronic tuberculosis.     

Licensing of natural killer cells by host major histocompatibility complex class I molecules

Self versus non-self discrimination is a central theme in biology from plants to vertebrates, and is particularly relevant for lymphocytes that express receptors capable of recognizing self-tissues and foreign invaders. Comprising the third largest lymphocyte population, natural killer (NK) cells recognize and kill cellular targets and produce pro-inflammatory cytokines. These potentially self-destructive effector functions can be controlled by inhibitory receptors for the polymorphic major histocompatibility complex (MHC) class I molecules that are ubiquitously expressed on target cells. However, inhibitory receptors are not uniformly expressed on NK cells, and are germline-encoded by a set of polymorphic genes that segregate independently from MHC genes. Therefore, how NK-cell self-tolerance arises in vivo is poorly understood. Here we demonstrate that NK cells acquire functional competence through 'licensing' by self-MHC molecules. Licensing involves a positive role for MHC-specific inhibitory receptors and requires the cytoplasmic inhibitory motif originally identified in effector responses. This process results in two types of self-tolerant NK cells--licensed or unlicensed--and may provide new insights for exploiting NK cells in immunotherapy. This self-tolerance mechanism may be more broadly applicable within the vertebrate immune system because related germline-encoded inhibitory receptors are widely expressed on other immune cells.     

Parameters for reliable results in genetic association studies in common disease.

It is increasingly apparent that the identification of true genetic associations in common multifactorial disease will require studies comprising thousands rather than the hundreds of individuals employed to date. Using 2,873 families, we were unable to confirm a recently published association of the interleukin 12B gene in 422 type I diabetic families. These results emphasize the need for large datasets, small P values and independent replication if results are to be reliable.     

The effect of reserpine on the Achilles reflex in normal young men

Zusammenfassung Reserpin in kleinen Dosen über eine Periode von 28 h führt zu einer Beschleunigung des Achillessehnenreflexes. Der Effekt ist statistisch gesichert, jedoch gering im Vergleich mit Veränderungen, die durch Schilddrüsenstörungen hervorgerufen werden.     

Adjusting for information content when comparing forecast performance

Cross‐institutional forecast evaluations may be severely distorted by the fact that forecasts are made at different points in time and therefore with different amounts of information. This paper proposes a method to account for these differences when analyzing an unbalanced panel of forecasts. The method computes the timing effect and the forecaster's ability simultaneously. Monte Carlo simulation demonstrates that evaluations that do not adjust for the differences in information content may be misleading. In addition, the method is applied to a real‐world dataset of 10 Swedish forecasters for the period 1999–2015. The results show that the ranking of the forecasters is affected by the proposed adjustment.     

Characteristics of white-tailed deer fawn beds, Black Hills, South Dakota

Forty-two white-tailed deer fawns ( Odocuileus virginianus dakotensis ) were captured and fitted with radio transmitters and observed from June through September 1991 and 1992 to determine diurnal bed site use in the Black Hills of South Dakota. Fawns were monitored biweekly during daylight hours and 259 bed sites were located. In addition, 301 random sites were measured for comparison. Of 31 habitat variables measured, 8 were significant to determine use by fawns for a bed site when compared with random sites. Sites used by fawns were in relatively open stands of ponderosa pine ( Pinus ponderosa ) with mean basal area of approximately 11 m 2 /ha compared to 16 m 2 /ha in random sites. Fawn bed sites had greater mean vegetation cover, which ranged from 28.1% to 36.0%, compared with 19.9% and 33.8% at random sites in 1991 and 1992, respectively. Mean vegetation height was 101 cm at bed sites compared to 75 cm at random sites. Current timber harvest standards for stocking levels of pine range from 14 m 2 /ha to 18 2 /ha in the Black Hills, which are similar to our random sites. These levels preclude adequate development of understory characteristics used by white-tailed deer fawns for bed sites.