Flash Activity Research Articles

SUMO modification regulates the transcriptional activity of FLASH

FLASH is a huge multifunctional nuclear protein that has been linked to apoptotic signalling, transcriptional control and Cajal body function. To gain further insight into the functions of the FLASH protein, we performed a yeast two-hybrid screening with FLASH as bait and identified the SUMO-conjugating enzyme Ubc9 as an interaction partner. The main interaction surface for Ubc9 was found in the C-terminal part of FLASH, which is also a target for sumoylation. We identified K1813 as the major sumoylation site in FLASH, being enhanced by the SUMO E3 ligases Pc2 and PIASy. Disruption of this SUMO-conjugation site did not change the speckled subnuclear localization of FLASH, but it caused a reduction in FLASH activity as measured in a Gal4-tethering assay. Interestingly, the SUMO-specific protease SENP1 activated FLASH in the same assay. Overall, our results point to a complex involvement of sumoylation in modulating the function of FLASH.

Seasonal variation of lightning activity over the Indian subcontinent

The seasonal variation of lightning flash activity over the Indian subcontinent (0°N–35°N and 60°E–100°E) is studied using the quality checked monthly lightning flash data obtained from lightning imaging sensor on board the Tropical Rainfall Measuring Mission satellite. This paper presents results of spatio-temporal variability of lightning activity over the Indian subcontinent. The study of seasonal total lightning flashes indicates that the lightning flash density values are in qualitative agreement with the convective activity observed over this region. Maximum seasonal total flash counts are observed during the monsoon season. The propagation of the inter-tropical convergence zone over this region is also confirmed. Synoptic conditions responsible for variation of lightning activity are also investigated with the help of an observed dataset. The mean monthly flash counts show a peak in the month of May, which is the month of maximum temperatures over this region. Maximum flash density (40.2 km−2 season−1) is observed during the pre-monsoon season at 25.2°N/91.6°E and the annual maximum flash density of 28.2 km−2 year−1 is observed at 33.2°N/74.6°E. The study of the inter-annual variability of flash counts exhibits bimodal nature with the first maximum in April/May and second maximum in August/September.

Newer antidepressants and gabapentin for hot flashes: an individual patient pooled analysis.

Nonhormonal treatment options have been investigated as treatments for hot flashes, a major clinical problem in many women. Starting in 2000, a series of 10 individual double-blind placebo-controlled studies has evaluated newer antidepressants and gabapentin for treating hot flashes. This current project was developed to conduct an individual patient pooled analysis of the data from these published clinical trials. Individual patient data were collected from the various study investigators who published their study results between 2000 and 2007. Between-study heterogeneity for study characteristics and patient populations was tested via chi2 tests before a pooled analysis. The primary end point, the change in hot flash activity from baseline to week 4, for each agent was calculated via both weighted and unweighted approaches, using the size of the study as the weight. Basic summary statistics were produced for hot flash score and frequency using the following three statistics: raw change, percent reduction, and whether or not a 50% reduction was achieved. This study included seven trials of newer antidepressants and three trials of gabapentin. The optimal doses (defined by individual study results) of the newer antidepressants paroxetine, venlafaxine, fluoxetine, and sertraline decreased hot flash scores by 41%, 33%, 13%, and 3% to 18% compared with the corresponding placebo arms, respectively. The three gabapentin trials decreased hot flashes by 35% to 38% compared with the corresponding placebo arms. Some newer antidepressants and gabapentin, within 4 weeks of therapy initiation, decrease hot flashes more than placebo.

In vivo Imaging of Superoxide Flashes in Skeletal Muscle

Emerging evidence suggests that reactive oxygen species (ROS) constitute a class of signaling molecules that regulate diverse cell functions including metabolism, muscle contractility and apoptosis. Recently we have developed and characterized a highly sensitive and reversible superoxide-selective probe, a circularly permuted yellow fluorescent protein (cpYFP), and demonstrated quantal and transient superoxide-producing events (superoxide flashes) within single mitochondria across multiple cell types (Wang et al, Cell, 132, 279).To further understand the physiological significance of flash events, we generated the pan-tissue mt-cpYFP transgenic mice expressing cpYFP in the mitochondria of multiple tissues. In vivo imaging of superoxide signals in gastrocnemius of transgenic mouse under anesthesia revealed mitochondrial superoxide flashes with similar properties (Fig). Further, superoxide flashes were also visualized in isolated skeletal muscle fibers transfected in vivo by electroporation with mt-cpYFP. Our findings support that mitochondrial superoxide flash activity is a physiologically relevant phenomenon that may participate in diverse aspects of cell function and signaling.View Large Image | View Hi-Res Image | Download PowerPoint Slide

V‐shaped VLF streaks recorded on DEMETER above powerful thunderstorms

We report the observation of unusual V‐shaped streaks on VLF spectra observed on the low‐altitude satellite DEMETER during its overcrossing of highly active (i.e., high lightning flash rate) thunderstorms. At ∼700 km, wave activity observed on the E‐field spectrograms at mid‐to‐low latitudes during nighttime are mainly dominated by upgoing 0+ whistlers and occasional reflected (from the other hemisphere) whistler components. Over a 3 year period, 87 events with V‐shaped streaks associated with intense and numerous 0+ whistlers in VLF range have been observed. Using the National Lightning Detection Network for cases above the North American region indicates that these V‐shaped streaks exclusively occur when DEMETER passes above intense isolated thunderstorms, with relatively high (tens per second) lightning flash activity. Using a new model of VLF propagation in the Earth‐ionosphere waveguide, and transionospheric leakage to the satellite altitude, it is shown that the funnel‐like “V” shape of the streaks is a simple consequence of the mapping to high altitude of frequency‐dependent position of mode interference nulls (and crests) within the Earth‐ionosphere waveguide.

Analysis of thunderstorm and lightning activity associated with sprites observed during the EuroSprite campaigns: Two case studies

During the summers of 2003 to 2006 sprites were observed over thunderstorms in France by cameras on mountain tops in Southern France. The observations were part of a larger coordinated effort, the EuroSprite campaigns, with data collected simultaneously from other sources including the French radar network for precipitation structure, Meteosat with images of cloud top temperature and the Météorage network for detection of cloud-to-ground (CG) flash activity. In this paper two storms are analyzed, each producing 27 sprite events. Both storms were identified as Mesoscale Convective Systems (MCS) with a trailing stratiform configuration (ST) and reaching a maximum cloud area of ~ 120,000 km 2. Most of the sprites were produced while the stratiform area was clearly developed and during periods of substantial increase of rainfall in regions with radar reflectivity between 30 and 40 dBZ. The sprite-producing periods followed a maximum in the CG lightning activity and were characterized by a low CG flash rate with a high proportion of + CG flashes, typically around 50%. All sprites were associated with + CGs except one which was observed after a − CG as detected by the Météorage network. This − CG was estimated to have − 800 C km charge moment change. The peak current of sprite-producing + CG (SP + CG) flashes was twice the average value of + CGs and close to 60 kA with little variation between the periods of sprite activity. The SP + CG flashes were further characterized by short time intervals before a subsequent CG flash (median value < 0.5 s) and with clusters of several CG flashes which suggest that SP + CG flashes often are part of multi-CG flash processes. One case of a lightning process associated with a sprite consisted of 7 CG flashes.

Evaluation of a new lightning-produced NO&amp;lt;sub&amp;gt;x&amp;lt;/sub&amp;gt; parameterization for cloud resolving models and its associated uncertainties

Abstract. A new parameterization of the lightning-produced NOx has been developed for cloud-resolving models. This parameterization is based on the unique characteristics of identifying which convective cells are capable of producing lightning based on a vertical velocity threshold and estimating the lightning flash rate in each convective cell from the non-precipitation and precipitation ice mass flux product. Further, the source location is filamentary instead of volumetric as in most previous parameterizations. This parameterization has been tested on the 10 July 1996 Stratospheric-Tropospheric Experiment: Radiation, Aerosols and Ozone (STERAO) storm. Comparisons of the simulated flash rate and NO mixing ratio (control experiment) with observations at different locations and stages of the storm show good agreement. An individual flash produces on average 121±41 moles of NO (7.3±2.5×1025 molecules NO) for the simulated high cloud base, high shear storm that is dominated by intra-cloud flash activity. Sensitivity tests have been performed to study the impact of the flash rate, the cloud-to-ground flash ratio, the flash length, the spatial distribution of the NO molecules, and the production rate per flash on the NO concentration and distribution. Results show a strong impact from the flash rate, the spatial placement of the lightning-NOx source and the number of moles produced per flash. On the other hand, the simulations show almost no impact from the different cloud-to-ground (CG) ratios and the lightning-NOx production rates per CG flash used as input to the model.

Superoxide Flashes in Single Mitochondria

In quiescent cells, mitochondria are the primary source of reactive oxygen species (ROS), which are generated by leakiness of the electron transport chain (ETC). High levels of ROS can trigger cell death, whereas lower levels drive diverse and important cellular functions. We show here by employing a newly developed mitochondrial matrix-targeted superoxide indicator, that individual mitochondria undergo spontaneous bursts of superoxide generation, termed "superoxide flashes." Superoxide flashes occur randomly in space and time, exhibit all-or-none properties, and provide a vital source of superoxide production across many different cell types. Individual flashes are triggered by transient openings of the mitochondrial permeability transition pore stimulating superoxide production by the ETC. Furthermore, we observe a flurry of superoxide flash activity during reoxygenation of cardiomyocytes after hypoxia, which is inhibited by the cardioprotective compound adenosine. We propose that superoxide flashes could serve as a valuable biomarker for a wide variety of oxidative stress-related diseases.

A phase III trial evaluating three doses of citalopram for hot flashes: NCCTG trial N05C9

9538 Background: Hot flashes are experienced by up to 75% of women and can negatively impact quality of life. Estrogen treatment has fallen out of favor, so new options are needed. Based on encouraging pilot data, this trial was designed to evaluate three doses of citalopram for effects on hot flashes. Methods: A randomized trial evaluated citalopram at doses of 10, 20 or 30 mg/day versus placebo for 6 weeks. Women recorded hot flashes for one week before starting treatment, then were titrated up to their assigned dose. The primary endpoint was change from baseline in hot flash score (frequency × severity) per a prospective daily hot flash diary. Secondary endpoints included hot flash frequency and activity interference. Toxicities were evaluated with a self-report questionnaire and NCI common terminology criteria. Eligibility included postmenopausal women with at least 14 bothersome hot flashes per week for the past month. A total of 50 patients per arm (N=200), provided 80% power for a two-sample t-test...

Newer antidepressants and gabapentin for hot flashes: An individual subject pooled analysis

9537 Background: Non-hormonal treatment options have been investigated as treatments for hot flashes, a major clinical problem in many women. Starting in 2000, a series of 10 individual double-blind, placebo-controlled studies involving newer antidepressants and gabapentin have evaluated these non-hormonal agents for decreasing hot flashes from a no-treatment baseline period, inclusive of all known such published trials through 2007. Methods: Individual patient data were collected. Between-study heterogeneity was tested via chi- square tests prior to a pooled analyses. The change in hot flash activity from baseline to week 4 for each agent was calculated via both weighted and unweighted approaches using the size of the study as the weight. The effect size was recalculated using an unweighted approach to test the sensitivity of the results relative to the influence of individual study sample sizes. Regression models and linear random effects were used to adjust for age, breast cancer history, and tamoxifen usage on hot flash activity. Results: Data from 1,341 patients indicated that paroxetine (2 studies), venlafaxine (1 study), fluoxetine (1 study), and sertraline (3 studies) decreased absolute hot flash scores by 41%, 33%, 13%, and 3%-18% more than did their corresponding placebo arms, respectively. As a group, the antidepressants decreased absolute hot flash scores by 26 % more than was seen with their corresponding placebo arms (P= 0.0001). The three gabapentin trials decreased absolute hot flashes by 35–38% more than did their corresponding placebo arms (P= 0.0001). Results were similar for the weighted and unweighted effect size approaches. Age, breast cancer history, and tamoxifen usage did not impact the findings. Conclusions: Newer antidepressants, as a group, and gabapentin decrease hot flashes significantly more than do placebos. There may be efficacy differences among the different antidepressants. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Concert Pharmaceuticals, JDS Pharmaceuticals, Wyeth

Depressed mood during the menopausal transition and early postmenopause

To characterize patterns of depressed mood during the menopausal transition (MT) in relation to age and MT-related factors and to assess the contribution of factors related to depressed mood at earlier points in the life span. Women (N = 508) were recruited from 1990 to 1992 from multiethnic neighborhoods and followed annually through 2005: 302 met the eligibility criteria for analyses reported here. The Center for Epidemiologic Studies Depression scale (CES-D) and a menstrual calendar were completed annually throughout the study. A subset of women provided a first morning voided urine specimen from 1997 through 2005. Urine samples were assayed for estrone glucuronide, follicle-stimulating hormone, testosterone, and cortisol. Mixed effects modeling was used to identify changes in CES-D scores over time, including the relationship to age, MT-related factors, and factors related to depression at other points in the life span (postpartum depression/blues, life stress, or family history of clinical depression). Age was modestly and negatively related to CES-D scores, but MT stage alone was not, except that the late MT stage was significantly related to depressed mood. Hot flash activity, life stress, family history of depression, history of "postpartum blues," sexual abuse history, body mass index, and use of antidepressants were also individually related to depressed mood; the hormonal assays and age of entry into and duration of late MT stage were unrelated. Although women in the late MT stage are vulnerable to depressed mood, factors that account for depressed mood earlier in the life span continue to have an important influence and should be considered in studies of etiology and therapeutics.

Pilot Evaluation of Flaxseed for the Management of Hot Flashes

The objective of this study was to evaluate, in a phase 2 pilot study, tolerability and the effect of 6 weeks of flaxseed therapy on hot flash scores in women not wishing to receive estrogen therapy. Eligibility included 14 hot flashes per week for at least 1 month. In the baseline week, participants took no study medication and documented the characteristics of their hot flashes. Thereafter, crushed flaxseed was administered at 40 g daily. Participants provided weekly toxicity reports and health-related quality of life information. The primary end point was a change in hot flash score prospectively reported in a daily hot flash diary. Thirty women were enrolled between June 17 and November 8, 2005. The mean decrease in hot flash scores after flaxseed therapy was 57% (median decrease 62%). The mean reduction in daily hot flash frequency was 50% (median reduction 50%), from 7.3 hot flashes to 3.6. Fourteen of the 28 participants (50%) experienced mild or moderate abdominal distention. Eight participants (29%) experienced mild diarrhea, one experienced flatulence, and six (21%) withdrew because of toxicities. This study suggests that dietary therapy decreases hot flash activity in women not taking estrogen therapy. This reduction is greater than what would be expected with placebo.

Ubiquinone (coenzyme Q 10) binding sites: Low dielectric constant of the gate prevents the escape of the semiquinone

The photosynthetic reaction center (RC) from purple bacteria is frequently used as a model for the interaction of ubiquinones (coenzyme Q) with membrane proteins. Single-turnover flash activation of RC leads to formation of the semiquinone (SQ) of the secondary acceptor quinone after odd flashes and quinol after even flashes. The ubiquinol escapes the binding site in ⩽1 ms, while the SQ does not leave the binding site for at least 5 min. Observed difference between these times suggests a large energetic barrier for the SQ. However, high apparent dielectric constant in the vicinity of the quinone ring (⩾25) results in a relatively small electrostatic energy of SQ stabilization. To resolve this apparent contradiction I suggest that a significant part of the kinetic stabilization of the SQ is achieved by the special topology of the binding site in which quinone can exit the binding site only by moving its headgroup toward the center of the membrane. The large energetic penalty of transferring the charged headgroup to the membrane dielectric can explain the observed kinetic stability of the SQ.

Regional Responses of Lightning Activities to Relative Humidity of the Surface

AbstractGlobal flash activity shows great contrast in different regions. Temperature and humidity are the essential meteorological factors that result in this difference. The regional response of lightning activities to the relative humidity (RH) is examined at different longitudes and latitudes using lightning data based on satellite and NCEP metrological observations (from 1995 to 2002). The result indicates that lightning activities respond positively to RH within longitudinal belts where RH is more than 74% and negatively for the region where RH is less than 72%. A similar response is found in latitudinal belts. It can be concluded that higher relative humidity results in more lighting activities at dry regions and less lighting activities at wet regions. The watershed of relative humidity for lightning production is about 72%~74%. Six special regions have been chosen to validate above results and an agreement has been found.

Comparison of lightning activity and radar-retrieved microphysical properties in EULINOX storms

A combined analysis of microphysical thunderstorm properties derived by C-band polarimetric Doppler radar measurements and lightning observations from two ground-based systems are presented. Three types of storms, a multicell, a supercell, and a squall line, that were observed during the European Lightning Nitrogen Oxides project (EULINOX) are investigated. Correlations are sought between the mass of rain, graupel, hail, and snow derived form radar observations at different height levels and the electrical activity, represented either by cloud-to-ground or intracloud flashes. These relationships are explained by connecting the radar-derived properties with the non-inductive charging process. For the multicell and the supercell storm, the lightning activity can be linearly correlated to both the hydrometeor total mass and class specific mass in the upper part of the storm. It is shown that the fractions of graupel and hail above the −20 °C-level in these storms positively correlate with the intracloud flash activity in the supercell, and negatively for the cloud-to-ground lightning frequency in the multicell. No such relation can be established for the squall line, indicating that the convective organization plays a crucial role in the lightning development. The analysis of the masses in the different storms shows that lightning activity cannot be parameterized by total mass alone, other parameters have to be identified. The results provide important information for all lightning studies that rely on bulk properties of thunderstorms, e.g., the parameterization of lightning in mesoscale models or the nowcasting of lightning by radar.

Inverted-polarity electrical structures in thunderstorms in the Severe Thunderstorm Electrification and Precipitation Study (STEPS)

Balloon-borne electric field soundings and lightning mapping data have been analyzed for three of the storms that occurred in the Severe Thunderstorm Electrification and Precipitation Study field program in 2000 to determine if the storms had inverted-polarity electrical structures. The polarities of all or some of the vertically stacked charge regions in such storms are opposite to the polarities observed at comparable heights in normal storms. Analyses compared the charge structures inferred from electric field soundings in the storms with charges inferred from three-dimensional lightning mapping data. Charge structures were inferred from electric field profiles by combining the one-dimensional approximation of Gauss's law with additional information from three-dimensional patterns in the electric field vectors. The three different ways of inferring the charge structure in the storms were found to complement each other and to be consistent overall. Charge deposition by lightning possibly occurred and increased the charge complexity of one of the storms. Many of the cloud flashes in each case were inverted-polarity flashes. Two storms produced ground flash activity comprised predominantly of positive ground flashes. One storm, which was an isolated thunderstorm, produced inverted-polarity cloud flashes, but no flashes to ground. The positive and negative thunderstorm charge regions were found at altitudes where, respectively, negative and positive charge would be found in normal-polarity storms. Thus, we conclude that these storms had anomalous and inverted-polarity electrical structures. Collectively, these three cases (along with the limited cases in the refereed literature) provide additional evidence that thunderstorms can have inverted-polarity electrical structures.

The relationship between lightning activity and surface wet bulb temperature and its variation with latitude in Australia

Convective Available Potential Energy (CAPE) is the driving force for thunderstorm development. CAPE is closely controlled by wet bulb temperature. The lightning activity measured by a network of ten lightning flash counters widely distributed across continental Australia was studied as a function of wet bulb temperature. At each of the stations, the monthly total of lightning ground flashes, N, increased sharply with the increase of the monthly mean daily maximum wet bulb temperature, Tw, max. The dependence was strongest in the tropics and became less pronounced at temperate latitudes. In Darwin (latitude 12° S), the lightning ground flash activity increased by over three orders of magnitude over a 7 °C range of Tw, max. The corresponding increases for Coffs Harbour (latitude 30° S) and for Melbourne (latitude 38° S) were about one and a half orders of magnitude and about half an order of magnitude, respectively, each over a 10 °C range of Tw, max. Power law approximations were derived for each of the ten stations and showed that the logarithm of N was directly proportional to the power, P, of Tw, max. The value of P showed a sharp exponential decrease with increasing latitude away from the equator.

Climatology of cloud-to-ground lightning in Georgia, USA, 1992-2003

A 12-year climatology of lightning cloud-to-ground flash activity for Georgia revealed the existence of three primary regions of high lightning activity: the area surrounding the Atlanta Metropolitan Statistical Area, east-central Georgia along the fall line, and along the Atlantic coast. Over 8.2 million ground flashes were identified during the climatology. July was the most active lightning month and December was the least active. Annual, seasonal, and diurnal distributions of cloud-to-ground flashes were also examined. These patterns illustrated the interacting effects of land cover, topography, and convective instability in enhancing lightning activity throughout Georgia. A synoptic analysis of the ten highest lightning days during the summer and winter revealed the importance of frontal boundaries in organizing convection and high lightning activity during both seasons. The prominence of convective instability during the summer and strong dynamical forcing in the winter was also found to lead to outbreaks of high lightning activity. Copyright  2005 Royal Meteorological Society.

Spatial and Temporal Distribution of Lightning Activities on the Tibetan Plateau

AbstractWe study the spatial and temporal distribution of lightning flash activity and its response to the thermodynamic characteristics on the Tibetan plateau by using the composite gridded lightning data from 1995 to 2002 observed by the satellite‐based sensors, provided by NASA LIS/OTD Science Team in Marshall Space Flight Center. The result shows that the mean flash density on the Tibetan plateau was 3 fl·a−1·km−2, and the maximum flash activity was on the central Plateau around (32°N, 88°E) with a peak value of 5.1 fl·a−1·km−2. The flash activity on the Plateau exhibited a seasonal variation and mainly occurred from June to August with a maximum flash activity period from late June to middle July. The diurnal variation of the maximum flash rate peaked during 14:00~16:00LT with exceptions of the prominent high mountain region, which peaked earlier, and prominent low basins, which peaked later. The flash activity on the Plateau strongly depends on the ground thermodynamic characteristics, and a positive correlation between lightning activity and Bowen ratio and ground sensitive heat flux is found during the plateau monsoon season. The correlation coefficient is 0.7 and 0.6, respectively, and the Bowen ratio could be an indicator of lightning producing efficiency.

Flash Activity in Two Synchronic Firefly Species (Coleoptera: Lampyridae)

Synchronic flashing in fireflies is a precisely timed behavior. This is a potentially useful tool to study sensory processing, the location and circuitry of the flash oscillator, and neuroeffector processing and coupling. Synchronic flashing, once thought to occur only in Southeast Asian fireflies, has recently been shown to be a prominent part of the behavior of a North American Photinus and Photuris species. To gain insights into the mechanisms of synchronic timing in fireflies, we compared spontaneous flashing and entrainment flashing in Photuris frontalis LeConte, a synchronic firefly found in Georgia's Coastal Plain, to analogous flashing in Pteroptyx malaccae Olivier, a synchronic firefly found in Malaysia. The timing of spontaneously produced flashes and entrainment flashes was recorded by photometry. Artificially produced, rhythmic stimulus flashes were used to induce a counterfeit synchrony (between subject fireflies and an LED), i.e., flash entrainment. We found that the spontaneously produced interflash intervals were repeated with a high degree of precision in P. frontalis and P. malaccae. However, the pattern of flashing was different during spontaneous flashing and flash entrainment. An isolated P. frontalis flashed intermittently during spontaneously flashing and entrainment flashing. Flash entrainment in P. frontalis started with an initial inhibition and then steady-state entrainment occurred with a fixed delay. In contrast, an isolated P. malaccae flashed continuously during spontaneous flashing and entrainment flashing. No initial inhibition occurred at the start of entrainment, and there was a gradual change in interflash interval until steady-state entrainment occurred at a fixed delay. We think that in-depth studies of the flash activities of different synchronic firefly species, including the locally available P. frontalis, could help our understanding of rhythmic temporal coordination of behavior by the nervous system.