Small-Scale Features in Pulsating Aurora

A field study was conducted from March 12-16, 2002 using a narrow-field intensified CCD camera installed at Churchill, Manitoba. The camera was oriented along the local magnetic zenith where small-scale black auroral forms are often visible. This analysis focuses on such forms occurring within a region of pulsating aurora. The observations show black forms with irregular shape and nonuniform drift with respect to the relatively stationary pulsating patches. The pulsating patches occur within a diffuse auroral background as a modulation of the auroral brightness in a localized region. The images analyzed show a decrease in the brightness of the diffuse background in the region of the pulsating patch at the beginning of the offphase of the modulation. Throughout the off phase the brightness of the diffuse aurora gradually increases back to the average intensity. The time constant for this increase is measured as the first step toward determining the physical process

Gene expression profiling of epithelium-associated FcRL4(+) B cells in primary Sjogren's syndrome reveals a pathogenic signature

In primary Sjögren's syndrome (pSS), FcRL4+ B cells are present in inflamed salivary gland tissue, within or in close proximity to ductal epithelium. FcRL4 is also expressed by nearly all pSS-related mucosa-associated lymphoid tissue (MALT) B cell lymphomas, linking FcRL4 expression to lymphomagenesis. Whether glandular FcRL4+ B cells are pathogenic, how these cells originate, and how they functionally differ from FcRL4- B cells in pSS is unclear. This study aimed to investigate the phenotype and function of FcRL4+ B cells in the periphery and parotid gland tissue of patients with pSS. First, circulating FcRL4+ B cells from 44 pSS and 54 non-SS-sicca patients were analyzed by flow cytometry. Additionally, RNA sequencing of FcRL4+ B cells sorted from parotid gland cell suspensions of 6 pSS patients was performed. B cells were sorted from cell suspensions as mini bulk (5 cells/well) based on the following definitions: CD19+CD27-FcRL4- ('naive'), CD19+CD27+FcRL4- ('memory'), and CD19+FcRL4+ B cells. We found that, although FcRL4+ B cells were not enriched in blood in pSS compared with non-SS sicca patients, these cells generally exhibited a pro-inflammatory phenotype. Genes coding for CD11c (ITGAX), T-bet (TBX21), TACI (TNFRSF13B), Src tyrosine kinases and NF-κB pathway-related genes were, among others, significantly upregulated in glandular FcRL4+ B cells versus FcRL4- B cells. Pathway analysis showed upregulation of B cell activation, cell cycle and metabolic pathways. Thus, FcRL4+ B cells in pSS exhibit many characteristics of chronically activated, pro-inflammatory B cells and their gene expression profile suggests increased risk of lymphomagenesis. We postulate that these cells contribute significantly to the epithelial damage seen in the glandular tissue and that FcRL4+ B cells are an important treatment target in pSS

Rescue of skeletal muscle α-actin–null mice by cardiac (fetal) α-actin

Skeletal muscle α-actin (ACTA1) is the major actin in postnatal skeletal muscle. Mutations of ACTA1 cause mostly fatal congenital myopathies. Cardiac α-actin (ACTC) is the major striated actin in adult heart and fetal skeletal muscle. It is unknown why ACTC and ACTA1 expression switch during development. We investigated whether ACTC can replace ACTA1 in postnatal skeletal muscle. Two ACTC transgenic mouse lines were crossed with Acta1 knockout mice (which all die by 9 d after birth). Offspring resulting from the cross with the high expressing line survive to old age, and their skeletal muscles show no gross pathological features. The mice are not impaired on grip strength, rotarod, or locomotor activity. These findings indicate that ACTC is sufficiently similar to ACTA1 to produce adequate function in postnatal skeletal muscle. This raises the prospect that ACTC reactivation might provide a therapy for ACTA1 diseases. In addition, the mouse model will allow analysis of the precise functional differences between ACTA1 and ACTC

Auroral Current and Electrodynamics Structure Measured by Two SOunding Rockets in Flight Simultaneously

On January 29, 2009, two identically instrumented sounding rockets were launched into a sub-storm auroral arc from Poker Flat Alaska. Labeled the Auroral Currents and Electrodynamics Structure (ACES) mission, the payloads were launched to different apogees (approx.350km and approx.120km) and staggered in time so as to optimize their magnetic conjunctions. The different altitudes provided simultaneous in-situ measurements of magnetospheric input and output to the ionosphere and the ionospheric response in the lower F and E region. Measurements included 3-axis magnetic field, 2-axis electric field nominally perpendicular to the magnetic field, energetic particles, electron and ion, up to 15keV, cold plasma temperature and density. In addition, PFISR was also operating in a special designed mode to measure electric field and density profiles in the plane defined by the rocket trajectories and laterally to either side of the trajectories. Observation of the measured currents and electrodynamics structure of the auroral form encountered are presented in the context of standard auroral models and the temporal/spatial limitations of mission designs

Auroral Current and Electrodynamics Structure (ACES) Observations of Ionospheric Feedback in the Alfven Resonator

In 2009, the Auroral Current and Electrodynamics Structure (ACES) High and Low sounding rockets were launched from the Poker Flat Rocket Range (PFRR) in Alaska, with the science objective of gathering in-situ data to quantify current closure in a discrete auroral arc. As ACES High crossed through the return current of an arc (that was monitored using an all sky camera from the ground at Fort Yukon), its instruments recorded clear Alfv nic signatures both poleward and equatorward of the return current region, but not within the main region of the return current itself. These data provide an excellent opportunity to study ionospheric feedback and how it interacts with the Alfv n resonator. We compare the observations with predictions and new results from a model of ionospheric feedback in the ionospheric Alfv n resonator (IAR) and report the significance and impact of these new data for the Magnetosphere-Ionosphere Coupling in the Alfv n Resonator (MICA) rocket mission to launch from PFRR this winter. MICA s primary science objectives specifically focus on better understanding the small-scale structure that the model predicts should exist within the return current region

A Rocket-Base Study of Auroral Electrodynamics Within the Current Closure Ionosphere

The Auroral Current and Electrodynamics Structure (ACES) mission consisted of two sounding rockets launched nearly simultaneously from Poker Flat Research Range, AK on January 29, 2009 into a dynamic multiple-arc aurora. The ACES rocket mission, in conjunction with the PFISR Radar, was designed to observe the three-dimensional current system of a stable auroral arc system. ACES utilized two well instrumented payloads flown along very similar magnetic field footprints, at various altitudes with small temporal separation between both payloads. ACES High, the higher altitude payload (apogee 360 km), took in-situ measurements of the plasma parameters above the current closure region to provide the input signature into the lower ionosphere. ACES Low, the low-altitude payload (apogee 130 km), took similar observations within the current closure region, where cross-field currents can flow. We present results comparing observations of the electric fields, magnetic fields, electron flux, and the electron temperature at similar magnetic footpoints between both payloads. We further present data from all-sky imagers and PFISR detailing the evolution of the auroral event as the payloads traversed regions connected by similar magnetic footpoints. Current measurements derived from the magnetometers on both payloads are further compared. We examine data from both PFISR and observations on the high-altitude payload which we interpreted as a signature of electron acceleration by means of Alfv n waves. We further examine all measurements to understand ionospheric conductivity and how energy is being deposited into the ionosphere through Joule heating. Data from ACES is compared against models of Joule heating to make inferences regarding the effect of collisions at various altitudes

Telomerase Inhibition Targets Clonogenic Multiple Myeloma Cells through Telomere Length-Dependent and Independent Mechanisms

Plasma cells constitute the majority of tumor cells in multiple myeloma (MM) but lack the potential for sustained clonogenic growth. In contrast, clonotypic B cells can engraft and recapitulate disease in immunodeficient mice suggesting they serve as the MM cancer stem cell (CSC). These tumor initiating B cells also share functional features with normal stem cells such as drug resistance and self-renewal potential. Therefore, the cellular processes that regulate normal stem cells may serve as therapeutic targets in MM. Telomerase activity is required for the maintenance of normal adult stem cells, and we examined the activity of the telomerase inhibitor imetelstat against MM CSC. Moreover, we carried out both long and short-term inhibition studies to examine telomere length-dependent and independent activities.Human MM CSC were isolated from cell lines and primary clinical specimens and treated with imetelstat, a specific inhibitor of the reverse transcriptase activity of telomerase. Two weeks of exposure to imetelstat resulted in a significant reduction in telomere length and the inhibition of clonogenic MM growth both in vitro and in vivo. In addition to these relatively long-term effects, 72 hours of imetelstat treatment inhibited clonogenic growth that was associated with MM CSC differentiation based on expression of the plasma cell antigen CD138 and the stem cell marker aldehyde dehydrogenase. Short-term treatment of MM CSC also decreased the expression of genes typically expressed by stem cells (OCT3/4, SOX2, NANOG, and BMI1) as revealed by quantitative real-time PCR.Telomerase activity regulates the clonogenic growth of MM CSC. Moreover, reductions in MM growth following both long and short-term telomerase inhibition suggest that it impacts CSC through telomere length-dependent and independent mechanisms

A Predictive Model of Intein Insertion Site for Use in the Engineering of Molecular Switches

Inteins are intervening protein domains with self-splicing ability that can be used as molecular switches to control activity of their host protein. Successfully engineering an intein into a host protein requires identifying an insertion site that permits intein insertion and splicing while allowing for proper folding of the mature protein post-splicing. By analyzing sequence and structure based properties of native intein insertion sites we have identified four features that showed significant correlation with the location of the intein insertion sites, and therefore may be useful in predicting insertion sites in other proteins that provide native-like intein function. Three of these properties, the distance to the active site and dimer interface site, the SVM score of the splice site cassette, and the sequence conservation of the site showed statistically significant correlation and strong predictive power, with area under the curve (AUC) values of 0.79, 0.76, and 0.73 respectively, while the distance to secondary structure/loop junction showed significance but with less predictive power (AUC of 0.54). In a case study of 20 insertion sites in the XynB xylanase, two features of native insertion sites showed correlation with the splice sites and demonstrated predictive value in selecting non-native splice sites. Structural modeling of intein insertions at two sites highlighted the role that the insertion site location could play on the ability of the intein to modulate activity of the host protein. These findings can be used to enrich the selection of insertion sites capable of supporting intein splicing and hosting an intein switch

Fumonisins affect the intestinal microbial homeostasis in broiler chickens, predisposing to necrotic enteritis

Fumonisins (FBs) are mycotoxins produced by Fusarium fungi. This study aimed to investigate the effect of these feed contaminants on the intestinal morphology and microbiota composition, and to evaluate whether FBs predispose broilers to necrotic enteritis. One-day-old broiler chicks were divided into a group fed a control diet, and a group fed a FBs contaminated diet (18.6 mg FB1+ FB2/kg feed). A significant increase in the plasma sphinganine/sphingosine ratio in the FBs-treated group (0.21 +/- 0.016) compared to the control (0.14 +/- 0.014) indicated disturbance of the sphingolipid biosynthesis. Furthermore, villus height and crypt depth of the ileum was significantly reduced by FBs. Denaturing gradient gel electrophoresis showed a shift in the microbiota composition in the ileum in the FBs group compared to the control. A reduced presence of low-GC containing operational taxonomic units in ileal digesta of birds exposed to FBs was demonstrated, and identified as a reduced abundance of Candidatus Savagella and Lactobaccilus spp. Quantification of total Clostridium perfringens in these ileal samples, previous to experimental infection, using cpa gene (alpha toxin) quantification by qPCR showed an increase in C. perfringens in chickens fed a FBs contaminated diet compared to control (7.5 +/- 0.30 versus 6.3 +/- 0.24 log10 copies/g intestinal content). After C. perfringens challenge, a higher percentage of birds developed subclinical necrotic enteritis in the group fed a FBs contaminated diet as compared to the control (44.9 +/- 2.22% versus 29.8 +/- 5.46%)

Climate mediates the effects of disturbance on ant assemblage structure

Many studies have focused on the impacts of climate change on biological assemblages, yet little is known about howclimate interacts with other major anthropogenic influences on biodiversity, such as habitat disturbance. Using a unique global database of 1128 local ant assemblages, we examined whether climate mediates the effects of habitat disturbance on assemblage structure at a global scale. Species richness and evenness were associated positively with temperature, and negatively with disturbance. However, the interaction among temperature, precipitation and disturbance shaped species richness and evenness. The effectwas manifested through a failure of species richness to increase substantially with temperature in transformed habitats at low precipitation. At low precipitation levels, evenness increased with temperature in undisturbed sites, peaked at medium temperatures in disturbed sites and remained low in transformed sites. In warmer climates with lower rainfall, the effects of increasing disturbance on species richness and evenness were akin to decreases in temperature of up to 98C. Anthropogenic disturbance and ongoing climate change may interact in complicated ways to shape the structure of assemblages, with hot, arid environments likely to be at greatest risk. © 2015 The Author(s) Published by the Royal Society. All rights reserved