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GATA-factor dependence of the multitype zinc-finger protein FOG-1 for its essential role in megakaryopoiesis.

The function of GATA transcription factors in diverse developmental contexts depends in part on physical interaction with cofactors of the Friend of GATA (FOG) family. However, previous studies indicate that FOG-1 may play a GATA-1-independent role in early megakaryopoiesis, suggesting that FOG proteins might act in a GATA factor-independent manner. Here, we have generated mouse knock-in (KI) mutants harboring a critical valine-to-glycine substitution in the amino-terminal zinc fingers of GATA-1 and GATA-2 to ablate FOG interaction. In contrast to male GATA-1(KI) (GATA-1 is located on the X-chromosome) or GATA-2(KI/KI) mice, compound GATA-1(KI) GATA-2(KI/KI) mutant mice display complete megakaryopoietic failure, a phenocopy of FOG-1(-/-) mice. We conclude that FOG-1 requires an interaction with either GATA-1 or -2 as part of its essential role in early megakaryopoiesis. On the basis of these and previous reports, we infer that GATA factor dependence is a critical aspect of FOG protein function.

Amino Acid Sequence↗

FOG-2, a heart- and brain-enriched cofactor for GATA transcription factors.

Members of the GATA family of zinc finger transcription factors have been shown to play important roles in the control of gene expression in a variety of cell types. GATA-1, -2, and -3 are expressed primarily in hematopoietic cell lineages and are required for proliferation and differentiation of multiple hematopoietic cell types, whereas GATA-4, -5, and -6 are expressed in the heart, where they activate cardiac muscle structural genes. Friend of GATA-1 (FOG) is a multitype zinc finger protein that interacts with GATA-1 and serves as a cofactor for GATA-1-mediated transcription. FOG is coexpressed with GATA-1 in developing erythroid and megakaryocyte cell lineages and cooperates with GATA-1 to control erythropoiesis. We describe a novel FOG-related factor, FOG-2, that is expressed predominantly in the developing and adult heart, brain, and testis. FOG-2 interacts with GATA factors, and interaction of GATA-4 and FOG-2 results in either synergistic activation or repression of GATA-dependent cardiac promoters, depending on the specific promoter and the cell type in which they are tested. The properties of FOG-2 suggest its involvement in the control of cardiac and neural gene expression by GATA transcription factors.

Amino Acid Sequence↗

Influence of film fog on radiographic caries diagnosis.

Increasing film speed may potentially jeopardize diagnostic quality because of a more rapid build up of fog and an ensuing decrease in image contrast. A standardized amount of fog was simulated by pre-exposing E-speed dental films before use to obtain images of extracted teeth with and without approximal caries. Three experiments were performed. In the first, no effort was made to compensate for the increased density caused by fog. In the other two, density was kept constant by reducing exposure and developing time respectively. Nine dentists recorded the presence and absence of caries using a rating scale to indicate diagnostic confidence. As a measure of diagnostic accuracy, the area under the binormal ROC curve was used and the values averaged across observers. The results showed that fog, up to a level of base plus fog of 0.6 optical density units, had no influence on the diagnostic accuracy in the absence of any compensation. When exposure was lowered to compensate for the increased density, significantly lower diagnostic accuracy was found. On the other hand, when developing time was decreased, no significant difference was found. Observers ranked radiographs with higher levels of fog as being of lower quality. However, no significant correlation was found between subjective ranking of image quality and diagnostic accuracy obtained from the same radiographs. It is concluded that relatively high levels of fog do not exert a negative influence on approximal caries diagnosis and no attempt should therefore be made to compensate for the increased density.

Bicuspid↗

Distance perception of vehicle rear lights in fog.

Perceptual difficulty is one of the main explanations given for the behavioral modifications and high accident rate associated with driving in fog. The present study investigates how fog and the characteristics of vehicle rear lights affect distance perception. Two experiments in a fog chamber (meteorological visibility range of 5-15 m) were run under conditions simulating nighttime fog. The participants gave verbal estimates of the distance (8-28 m) of vehicles simulated by rear-light arrangements. The results revealed an average increase of 60% in the perceived distance of vehicles in fog as compared with normal visibility conditions. Distance overestimation was particularly pronounced when the vehicle had only 1 fog light instead of 2 and when the lights were close together. No effect of light height was observed. These results suggest that the perception of vehicle distance in nighttime fog could be significantly improved by the presence of 2 lights with maximal spacing. Actual or potential applications of this research include vehicle rear light design.

Accidents, Traffic↗

[Effect of fog on diurnal changes in peak expiratory flow rates in an asthmatic].

To evaluate the effects of fog on asthmatics, we analyzed the symptoms of a 45-year-old female during the foggy season and the relation between diurnal peak expiratory flow rate (PEFR) and fog and other meteorological factors. Her asthma attacks had been induced by specific smells: perfume, smoke from burning grass or industrial smoke. Two years previously, she had moved to the suburbs of Sapporo, where fog frequently occurs. From that time her asthmatic symptoms had been exacerbated, so it was suspected that the fog might have had some influence. We analyzed 251 measures of PEFR from June to August 1994. The average and standard deviation of PEFR in the absence of fog and specific smells was 403 +/- 40 L/min (n = 195). PEFR was significantly lower (p < 0.01) when it was foggy (347 +/- 60 L/min; n = 40), when specific smells were present (333 +/- 60 L/min; n = 5) and when there were both fog and specific smells (340 +/- 53 L/min: n = 11). On the other hand, there were no changes associated with other meteorological factors: barometric pressures, relative humidity, mean temperature, minimal temperature and most frequent wind direction. These results suggested that the inhalation of fog decreases PEFR and is an exacerbating factor in bronchial asthma.

Asthma↗

Fogging on T2-weighted MR after acute ischaemic stroke: how often might this occur and what are the implications?

"Fogging" is the temporary loss of visibility of an infarct on CT which occurs in the subacute phase at about 2 weeks after stroke. It occurs in up to 40% of medium to large infarcts on CT. It is unclear whether or how often fogging occurs on T2-weighted MR, but if it does occur, it can cause underestimation of true infarct size. This study examined the possible frequency and time scale of "fogging" on T2-weighted MR. We conducted a blinded, independent review of prospectively collected MR scans from patients with symptoms of cortical ischaemic stroke, scanned sequentially up to 7 weeks after stroke. On each scan maximum infarct area was measured, and the infarct extent and swelling were coded on a validated scale. "Fogging" was suggested by reduced infarct extent between initial and subsequent scans. In 30 patients (with 74 scans) there was some apparent "fogging" in 50% of patients between 6 and 36 days (median 10 days) after stroke. Reduction in infarct extent on T2-weighted MR which may be attributed to "fogging" occurs in a significant proportion of patients with cortical infarcts. This may lead to an underestimation of true final infarct extent. This suggests that true infarct extent on T2-weighted MR can probably only be assessed on scans obtained beyond 7 weeks after stroke.

Brain Infarction↗

Photochemical oxidant pollution and vegetation: effects of mixtures of gases, fog and particles.

Photochemical 'smog' contains mixtures of gases (e.g. ozone, nitrogen dioxide), and dry particles (e.g. nitrates). Intermittent fog in the same geographical area can be acidic with high concentrations of nitric acid. Results from recent field studies in the Los Angeles Basin have emphasized the relative toxicity of these components of photochemical air pollution. Studies have focused on gaseous+fog or gaseous+dry particulate effects on conifers, gaseous+fog effects on crops, and the effects of trace pollutants produced during generation of ozone on crops. Data from these studies indicate that direct alterations in growth and physiological responses were observed only with gaseous pollutants (primarily ozone), or repeated applications of highly acidic fogs (pH < 2.7). Direct particle dry deposition effects are unclear. Few interactions have been found between gaseous pollutants and acidic fog. Charcoal-filtered open-top chambers are highly effective in removing pollutants in the following order: fog (100%) > peroxyacetyl nitrate > ozone > nitrogen dioxide > sulfur dioxide > nitrate ion > ammonium ion > sulfate ion. However, nitric oxide concentrations are higher in charcoal-filtered chambers than in ambient air. The studies point out the importance of considering other components of photochemical pollution in addition to ozone, especially when investigating subtle, long-term effects on vegetation.

Journal Article↗

Are freezing of gait (FOG) and panic related?

We studied 109 consecutive patients who were unselected for freezing of gait (FOG), anxiety, depression, or panic attacks. All patients completed a panic assessment, the Hamilton Anxiety Scale and the Hamilton Depression Scale. Patients were divided into those with FOG or no FOG based on their answer to the FOG question on the Activities of Daily Living part of the UPDRS. Patients with FOG were more disabled, had more "wearing off", dyskinesia, leg dystonia, and postural instability. They were also more anxious and more likely to panic. FOG, in many patients, is increased by anxiety and panic.

Aged↗

FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium.

We disrupted the FOG-2 gene in mice to define its requirement in vivo. FOG-2(-/-) embryos die at midgestation with a cardiac defect characterized by a thin ventricular myocardium, common atrioventricular canal, and the tetralogy of Fallot malformation. Remarkably, coronary vasculature is absent in FOG-2(-/-) hearts. Despite formation of an intact epicardial layer and expression of epicardium-specific genes, markers of cardiac vessel development (ICAM-2 and FLK-1) are not detected, indicative of failure to activate their expression and/or to initiate the epithelial to mesenchymal transformation of epicardial cells. Transgenic reexpression of FOG-2 in cardiomyocytes rescues the FOG-2(-/-) vascular phenotype, demonstrating that FOG-2 function in myocardium is required and sufficient for coronary vessel development. Our findings provide the molecular inroad into the induction of coronary vasculature by myocardium in the developing heart.

Animals↗

Use of altered specificity mutants to probe a specific protein-protein interaction in differentiation: the GATA-1:FOG complex.

GATA-1 and FOG (Friend of GATA-1) are each essential for erythroid and megakaryocyte development. FOG, a zinc finger protein, interacts with the amino (N) finger of GATA-1 and cooperates with GATA-1 to promote differentiation. To determine whether this interaction is critical for GATA-1 action, we selected GATA-1 mutants in yeast that fail to interact with FOG but retain normal DNA binding, as well a compensatory FOG mutant that restores interaction. These novel GATA-1 mutants do not promote erythroid differentiation of GATA-1- erythroid cells. Differentiation is rescued by the second-site FOG mutant. Thus, interaction of FOG with GATA-1 is essential for the function of GATA-1 in erythroid differentiation. These findings provide a paradigm for dissecting protein-protein associations involved in mammalian development.

Amino Acid Sequence↗

Organic matter in central California radiation fogs.

Organic matter was studied in radiation fogs in the San Joaquin Valley of California during the California Regional Particulate Air Quality Study (CRPAQS). Total organic carbon (TOC) concentrations ranged from 2 to 40 ppm of C. While most organic carbon was found in solution as dissolved organic carbon (DOC), 23% on average was not dissolved inside the fog drops. We observe a clear variation of organic matter concentration with droplet size. TOC concentrations in small fog drops (<17 microm) were a factor of 3, on average, higher than TOC concentrations in larger drops. As much as half of the dissolved organic matter was determined to have a molecular weight higher than 500 Da. Deposition fluxes of organic matter in fog drops were high (0.5-4.3 microg of C m(-2) min(-1)), indicating the importance of fog processing as a vector for removal of organic matter from the atmosphere. Deposition velocities of organic matter, however, were usually found to be lower than deposition velocities for fogwater, consistent with the enrichment of the organic matter in smaller fog drops with lower terminal settling velocities.

Air Movements↗

Effects of naturally-occurring acid fog on inflammatory mediators in airway and pulmonary functions in asthmatic patients.

Floating fog occurs every summer in Kushiro City in Japan, and the annual average of fog water pH in the past 4 years has been under 5.0. We previously reported that epidemiologically fog was the most important positive factor contributing to increased hospital visits of asthmatic patients compared with other meteorological values and air pollutants. This study aimed to investigate the mechanism of the effects of naturally-occurring acid fog on asthmatic patients. We compared pulmonary functions and inflammatory mediators in induced sputum between the foggy (July 1995) and the non-foggy (May 1996) season, and assessed airway responsiveness to hypo-osmolar aerosol. Forty-four out of 118 asthmatic patients of Kushiro City residents participated, pulmonary function tests were completed in 36 patients, and sputum data were available in 26 patients in both seasons. Percent forced expiratory volume in 1 sec (FEV1) was significantly (P< 0.05) decreased, and % peak expiratory flow rate (PEFR) had a trend to decrease in the foggy season more than in the non-foggy, and sputum eosinophil cationic protein (ECP) and interleukin (IL)-8 were higher in the foggy season but not significantly. A moderate inverse correlation was revealed between sputum ECP and %PEFR in the foggy season (r= -0.55, P<0.005). Subjects were divided into two groups according to the best PEFR; one had >10% lower PEFR levels in the foggy season than in the non-foggy season (Group A, n = 7), the remainder did not (Group B, n = 19). In group A, sputum ECP was significantly increased (P< 0.01) in the foggy season, but there were no changes in IL-8 and prostaglandin D2. Ultrasonic nebulized distilled water provocation test revealed no differences between group A and B. These results suggested that eosinophilic inflammation rather than hypo-osmolar effect of fog might contribute to respiratory deterioration by inhalation of naturally-occurring acid fog.

Acid Rain↗

Color appearance of surfaces viewed through fog.

How do the colors of surfaces seen through fog depend on the chromatic properties of the fog? Prior work (e.g. Chen and D'Zmura, 1998 Perception 27 595-608) shows that the colors of surfaces seen through a transparent filter can be described by a convergence model. The convergence model takes into account color shift and change in contrast. Whether the convergence model can also be applied to fog was tested experimentally with an asymmetric matching task. In computer graphic simulation, observers adjusted the color of a surface seen through fog in order to match the color of a surface seen in the absence of fog. The convergence model fits the data well. The results suggest that the color constancy revealed in this task with fog is described best by a model that takes into account both shift in color and change in contrast.

Color Perception↗

Specification of germ cell fates by FOG-3 has been conserved during nematode evolution.

Rapid changes in sexual traits are ubiquitous in evolution. To analyze this phenomenon, we are studying species of the genus Caenorhabditis. These animals use one of two different mating systems-male/hermaphroditic, like the model organism Caenorhabditis elegans, or male/female, like C. remanei. Since hermaphrodites are essentially females that produce sperm for self-fertilization, elucidating the control of cell fate in the germ line in each species could provide the key to understanding how these mating systems evolved. In C. elegans, FOG-3 is required to specify that germ cells become sperm. Thus, we cloned its homologs from both C. remanei and C. briggsae. Each species produces a single homolog of FOG-3, and RNA-mediated interference indicates that FOG-3 functions in each species to specify that germ cells develop as sperm rather than as oocytes. What factors account for the different mating systems? Northern analyses and RT-PCR data reveal that the expression of fog-3 is always correlated with spermatogenesis. Since the promoters for all three fog-3 genes contain binding sites for the transcription factor TRA-1A and are capable of driving expression of fog-3 in C. elegans hermaphrodites, we propose that alterations in the upstream sex-determination pathway, perhaps acting through TRA-1A, allow spermatogenesis in C. elegans and C. briggsae XX larvae but not in C. remanei.

Amino Acid Sequence↗

Fog-induced respiratory responses are attenuated by nedocromil sodium in humans.

Fog inhalation induces cough and bronchoconstriction in patients with asthma, but only cough in normal subjects; whether it also influences the pattern of breathing is unclear. Nedocromil sodium (NCS) inhibits the cough response to inhalation of several pharmacological agents but its effects on fog-induced cough and changes in the pattern of breathing are unknown. We evaluated the effects of no drug, placebo, and 4- and 8-mg NCS administration on the cough threshold and changes in the pattern of breathing during fog inhalation in 14 healthy subjects. Measurements of tidal volume (VT), duration of inspiratory and expiratory times (TI and TE, respectively), total duration of the respiratory cycle (TT), mean inspiratory flow (VT/TI), duty cycle (TI/TT), respiratory frequency (f, 60/TT), and inspiratory minute ventilation (V I) were obtained by inductive plethysmography. Median cough threshold values were unaffected by placebo, but were increased (p < 0.01) by both NCS doses. In no-drug and placebo trials, inhalation of the threshold fog concentration caused increases in both VT/TI and V I (p always < 0.05) due to selective increases (p < 0.01) in VT. These changes were markedly attenuated by both NCS doses administration. Thus, fog induces coughing and increases in VT, VT/ TI, and V I in healthy subjects; NCS possesses antitussive effects and attenuates fog-induced changes in the pattern of breathing, possibly through inhibition of rapidly adapting "irritant" receptors.

Adult↗

Acute exposure to acid fog. Effects on mucociliary clearance.

Submicrometric sulfuric acid (H2SO4) aerosol can affect mucociliary clearance without eliciting irritative symptoms or changes in pulmonary function. The effect of larger fog droplets containing H2SO4 on mucociliary clearance is unknown. We quantified mucociliary clearance from the trachea (n = 4) and small airways (n = 7) of young healthy male adults after an acute exposure to H2SO4 fog (MMAD = 10.3 microns; pH = 2.0; liquid water content = 481 +/- 65 mg/m3; osmolarity = 30 mOsm). Acid fog (AF) or saline fog (SF) (10.9 microns; 492 +/- 116 mg/m3; 30 mOsm) was administered for 40 min of unencumbered breathing (no mouth-piece) at rest and for 20 min of exercise sufficient to produce oronasal breathing. Fog exposures were followed by a methacholine (MCh) challenge (a measure of airway reactivity) or inhalation of technetium-99M radioaerosol (MMAD = 3.4 microns) on 2 study days each. Changes in symptoms and forced ventilatory function were also assessed. Clearance was quantified from computer-assisted analyses of gamma camera images of the lower respiratory tract in terms of %removal/min of the radiolabel from the trachea 25 min after inhalation and from the outer zone of the right lung after 1.9 to 3 h. Symptoms, forced ventilatory function, and MCh response were unaffected by either fog. Tracheal clearance was more rapid in four of four subjects after AF (0.83 +/- 1.58% removal/min) compared with that after SF (-0.54 +/- 0.85% removal/min). Outer zone clearance was more rapid in six of seven subjects after AF (0.22 +/- 0.15% removal/min) compared with that after SF (0.01 +/- 0.09% removal/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of long-range transport of air mass on the ionic components in radiation fog in northern Japan.

Water samples from radiation and upslope types of fog were collected at Takanosu Basin and Hachimantai mountain range of Akita Prefecture in northern Japan, respectively. The effect of the long-range transport of pollutants from the Asian Continent to the basin and the mountain range on the chemical characteristics of two types of fog was studied using chemical analysis data for the water samples as well as the back-trajectories of the air mass. In particular, non-sea-salt (nss)-SO4(2-) of radiation fog provided a much higher concentration than that of upslope fog, which suggests that nss-SO4(2-) might be transported mainly from the Asian Continent. The transport and uptake mechanism of pollutants in the radiation fog water were explained based on their accumulation in the basin due to anticyclonic subsidence and by the long-lasting fog behavior.

Journal Article↗

Two-year follow-up study of the effect of acid fog on adult asthma patients.

Acid fog is a complex mixture of atomospheric pollutants containing multiple stimuli that may be capable of inducing bronchoconstriction. To investigate the effect of ambient acid fog on bronchoconstriction, we examined the relation between the hospital visit for asthma symptoms of 102 patients and various meteorological conditions for over the two-year period from January 1992 to December 1993. Dense fog occurs frequently every summer in Kushiro, a city located in Hokkaido, northernmost island in Japan. The acidity of the fog ranged from pH 3.32 to 6.91 (mean pH = 5.05) during this period. A significant increase (p < 0.05) of hospital visits on a foggy day was found in 9 cases, and a tendency (p < 0.10) was found in 10 cases. The odds ratio for a hospital visit on a high water vapor pressure day (> 12 h Pa) was significantly high (p < 0.01) in 5 cases among the above 19 cases. To exclude the effect of high water vapor pressure, the data was restricted to the condition of a foggy day with low water vapor pressure (< 12 hPa); 9 patients had a significant increase (p < 0.05) in hospital visits on such a day. These results indicated that hospital visits for asthma symptoms was increased on acid fog days in 8.8% of adult asthma patients. Inhalation of naturally occurring acid fog may have adverse effects on the respiratory tract of the asthmatic patient.

Acids↗