Genetics of Aux/IAA and ARF action in plant growth and development.

Dramatic advances in our understanding of auxin signal-response pathways have been made in recent years. Much of this new knowledge has come through the study of mutants in Arabidopsis thaliana. Mutations have been identified in a wide variety of auxin-response components, including auxin transporters, protein kinases and phosphatases, components of a ubiquitin-proteosome pathway, and transcriptional regulators. This review focuses on mutations that affect auxin-modulated transcription factors, in particular those in the Aux/IAA and AUXIN RESPONSE FACTOR (ARF) genes. Mutants in members of these related gene families exhibit phenotypes that indicate both unique localized functions, as well as overlapping redundant functions, throughout plant development - from embryogenesis to flowering. Effects of specific mutations on Aux/IAA and ARF protein functions at the biochemical and physiological levels will be discussed. We will also discuss potential mechanisms for interactions between auxin and light response pathways that are suggested by these mutants.

Increased lung compliance in response to a moderate hyperoxic exposure.

With deep saturation diving a reduction in vital capacity caused by oxygen toxicity may be opposed by a training effect of respiratory muscles due to increased gas density and work of breathing. We measured lung and chest wall mechanics before and after a 28-day saturation dive to a pressure of 0.25 MPa with the same profile of oxygen exposure as in a deep dive to a pressure of 3.7 MPa; 40 kPa during the isopression phase and 50 kPa during the decompression phase. Eight males aged 22-28 yr served as subjects. The measurements included dynamic lung volumes, static lung compliance, lung recoil pressure, and maximal respiratory pressures. Only one subject had decreased lung compliance and increased recoil pressure after the dive. The others had an increase in compliance and decrease in recoil pressure. There was a significant increase in inspiratory lung compliance (P = 0.041) and a trend for a decrease in lung recoil pressure (P = 0.061). We found no change in forced vital capacity, but decreases in forced expired volume in 1 s (P = 0.049) and forced midexpiratory flow rate (P = 0.009) were noted. There were no changes in maximal respiratory pressures. These findings are opposite to the classical findings associated with pulmonary oxygen toxicity. The results may reflect an increase in surfactant production and turnover as an early adaptive response to hyperoxic stress.

Body mass, fat percentage, and fat free mass as reference variables for lung function: effects on terms for age and sex.

BACKGROUND: Sex specific cross sectional reference values for lung function indices usually employ a linear model with terms for age and stature. The effects of also matching for body mass index (BMI = mass/stature(2)) or its components, fat percentage of body mass (fat%) and fat free mass index (FFMI = fat free mass/stature(2)) were studied. METHODS: The subjects were 458 asymptomatic male and female non-smokers (383 men) and 22 female ex-smokers. Measurements were made of ventilatory capacity, lung volumes, transfer factor (diffusing capacity, single breath CO method), and body composition (skinfold method). Linear and proportional regression models were used. RESULTS: Terms for fat% and FFMI significantly improved the accuracy of reference values for all the primary lung function indices. The improvements in subjects with atypical physiques (fat% and FFMI at the ends of the distributions for the subjects) were in the range 0.3-2.3 SD compared with conventional regression equations. The new partial regression coefficients on age were independent of age related changes in body fat. The coefficient for total lung capacity (TLC) on age in men was now positive. Most differences between the sexes were eliminated. A term for BMI improved the descriptions of subdivisions of TLC but lacked the other advantages. CONCLUSION: Allowance for fat% and FFMI increases the accuracy of reference equations for lung function, particularly for subjects with a lot of fat and little muscle or vice versa. Allowance for BMI is less informative.

Roles and activities of Aux/IAA proteins in Arabidopsis.

Auxin induces various distinct developmental responses, partly by regulating gene expression. The Aux/IAA genes are a large gene family, many of which are induced by auxin. Work on Arabidopsis Aux/IAA genes has begun to reveal that they can regulate development and auxin-induced gene expression. Furthermore, auxin responses require Aux/IAA protein turnover. Finally, recent evidence suggests that Aux/IAA proteins can mediate light responses. Work in the near future should test whether Aux/IAA proteins are antennae that connect auxin and light signals to endogenous developmental responses.

Preeclampsia associated with chronic hypertension among African-American and White women.

OBJECTIVE: To examine the racial differences in preeclampsia/eclampsia (preeclampsia) associated with chronic hypertension among African-American and White women. METHODS: Using hospital discharge summary records from the National Hospital Discharge Survey from 1988 to 1996, we conducted a case-control study to assess the risk of preeclampsia among women with chronic hypertension in two separate identical models: one for African-American and another for White women. Cases were pregnant women who developed preeclampsia. Controls were women without preeclampsia. The main exposure was chronic hypertension. Logistic regression was used to derive odds ratios (OR) and 95% confidence intervals (CI) and to assess interaction between hypertension and preeclampsia. Population attributable risk percent associated between chronic hypertension and preeclampsia was calculated for each ethnic group. RESULTS: Preeclampsia was more than eleven times likely among women with chronic hypertension compared to normotensive women for both African-American (OR = 12.4, 95% CI = 10.2-15.2) and White women (OR = 11.3, 95% CI = 9.7-13.2). Among African-American women, we found an interaction between chronic hypertension and region on preeclampsia. The effect of region magnified the risk of preeclampsia associated with chronic hypertension in general for African-American women, but the effect was lower for the Southern region (OR = 8.9, 95% CI = 6.4-12.3). We also found that the point estimate of population attributable risk percent of preeclampsia attributable to chronic hypertension was significantly higher for African-American women (10.3, 95% CI = 8.6-12.5) compared to White women (5.3, 95% CI = 4.7-6.4). CONCLUSION: The more than eleven-fold higher risk of preeclampsia among both African-American and White women with chronic hypertension compared to normotensive women underscores the potential risk of chronic hypertension for adverse pregnancy outcomes. Furthermore, the two-fold higher population attributable risk percent of preeclampsia among African-American compared to White women quantifies the burden of preeclampsia attributable to chronic hypertension, and indicates a greater opportunity for prevention.

Coronary heart disease in African Americans.

African Americans have the highest overall mortality rate from coronary heart disease (CHD) of any ethnic group in the United States, particularly out-of-hospital deaths, and especially at younger ages. Although all of the reasons for the excess CHD mortality among African Americans have not been elucidated, it is clear that there is a high prevalence of certain coronary risk factors, delay in the recognition and treatment of high-risk individuals, and limited access to cardiovascular care. The clinical spectrum of acute and chronic CHD in African Americans is similar to that in whites. However, African Americans have a higher risk of sudden cardiac death and present more often with unstable angina and non-Q-wave myocardial infarction than whites. African Americans have less obstructive coronary artery disease on angiography, but may have a similar or greater total burden of coronary atherosclerosis. Ethnic differences in the clinical manifestations of CHD may be explained largely by the inherent heterogeneity of the coronary syndromes, and the disproportionately high prevalence and severity of hypertension and type 2 diabetes in African Americans. Identification of high-risk individuals for vigorous risk factor modification-especially control of hypertension, regression of left ventricular hypertrophy, control of diabetes, treatment of dyslipidemia, and smoking cessation--is key for successful risk reduction.

AXR2 encodes a member of the Aux/IAA protein family.

The dominant gain-of-function axr2-1 mutation of Arabidopsis causes agravitropic root and shoot growth, a short hypocotyl and stem, and auxin-resistant root growth. We have cloned the AXR2 gene using a map-based approach, and find that it is the same as IAA7, a member of the IAA (indole-3-acetic acid) family of auxin-inducible genes. The axr2-1 mutation changes a single amino acid in conserved domain II of AXR2/IAA7. We isolated loss-of-function mutations in AXR2/IAA7 as intragenic suppressors of axr2-1 or in a screen for insertion mutations in IAA genes. A null mutant has a slightly longer hypocotyl than wild-type plants, indicating that AXR2/IAA7 controls development in light-grown seedlings, perhaps in concert with other gene products. Dark-grown axr2-1 mutant plants have short hypocotyls and make leaves, suggesting that activation of AXR2/IAA7 is sufficient to induce morphological responses normally elicited by light. Previously described semidominant mutations in two other Arabidopsis IAA genes cause some of the same phenotypes as axr2-1, but also cause distinct phenotypes. These results illustrate functional differences among members of the Arabidopsis IAA gene family.

The histidine kinase-related domain participates in phytochrome B function but is dispensable.

Phytochromes are photoreceptors that control many plant light responses. Phytochromes have two carboxyl-terminal structural domains called the PAS repeat domain and the histidine kinase-related domain. These domains are each related to bacterial histidine kinase domains, and biochemical studies suggest that phytochromes are light-regulated kinases. The PAS repeat domain is important for proper phytochrome function and can interact with putative signaling partners. We have characterized several new phytochrome B mutants in Arabidopsis that express phyB protein, three of which affect the histidine kinase-related domain. Point mutations in the histidine kinase-related domain cause phenotypes similar to those of null mutants, indicating that this domain is important for phyB signaling. However, a truncation that removes most of the histidine kinase-related domain results in a phyB molecule with partial activity, suggesting that this domain is dispensable. These results suggest that phytochromes evolved in modular fashion. We discuss possible functions of the histidine kinase-related domain in phytochrome signaling.

Independent action of ELF3 and phyB to control hypocotyl elongation and flowering time.

Light regulates various aspects of plant growth, and the photoreceptor phytochrome B (phyB) mediates many responses to red light. In a screen for Arabidopsis mutants with phenotypes similar to those of phyB mutants, we isolated two new elf3 mutants. One has weaker morphological phenotypes than previously identified elf3 alleles, but still abolishes circadian rhythms under continuous light. Like phyB mutants, elf3 mutants have elongated hypocotyls and petioles, flower early, and have defects in the red light response. However, we found that elf3 mutations have an additive interaction with a phyB null mutation, with phyA or hy4 null mutations, or with a PHYB overexpression construct, and that an elf3 mutation does not prevent nuclear localization of phyB. These results suggest that either there is substantial redundancy in phyB and elf3 function, or the two genes regulate distinct signaling pathways.

Phytochromes are Pr-ipatetic kinases.

A series of new studies reveal how the red/far-red light photoreceptors called phytochromes act. Phytochrome A and phytochrome B each move to the nucleus when activated by light, and phytochrome A is a kinase. Phytochrome-interacting proteins provide candidate signal transduction components and a recent physiological study suggests how phyA may mediate responses to far-red light. Regulation of phytochrome nuclear localization and kinase activities creates multiple phytochrome species, which may each have different regulatory activities.

Subacute effects of inspiratory resistive loading and head-out water immersion on pulmonary function.

Extrathoracic airways obstruction and scuba diving may induce pulmonary edema, probably because of increased hydrostatic transmural capillary pressure in the lung. This study was designed to examine the subacute pulmonary effects of the combined exposure to inspiratory resistive loading and immersion, as in scuba diving. Two groups each of eight healthy men were exposed to head-out water immersion in thermoneutral water for 40 min with or without an added inspiratory resistive load. At flows of 0.5 and 1.0 liter x s, the measured resistances were 4.4 and 9.0 hPa x s(-1) x liter(-1), respectively. Pulmonary function, including a flow-volume loop and transfer factor of the lung for carbon monoxide (Tlco, was measured before and 60 min after the end of the exposures. Body fluid balance was restored in the first 15 min after exposure, and Tlco was always corrected to a hemoglobin concentration of 146 g x liter(-1). There was a significant reduction in Tlco of 7.3+/-5.5% (P < 0.01) after the combined exposure to head-out water immersion and inspiratory resistive load. No changes in pulmonary function were seen after exposure to head-out water immersion or inspiratory resistive loading alone. The change in Tlco was normalized within 24 h. Submersion and resistance in breathing apparatus may contribute to the changes in pulmonary function seen immediately after dives. The nature of the exposure in these experiments and the time for recovery indicate that these changes are mechanically induced, and may not contribute to the long-term effects of diving on the lung.

Control of auxin-regulated root development by the Arabidopsis thaliana SHY2/IAA3 gene.

The plant hormone auxin controls many aspects of development and acts in part by inducing expression of various genes. Arabidopsis thaliana semidominant shy2 (short hypocotyl) mutations cause leaf formation in dark-grown plants, suggesting that SHY2 has an important role in regulating development. Here we show that the SHY2 gene encodes IAA3, a previously known member of the Aux/IAA family of auxin-induced genes. Dominant shy2 mutations cause amino acid changes in domain II, conserved among all members of this family. We isolated loss-of-function shy2 alleles including a putative null mutation. Gain-of-function and loss-of-function shy2 mutations affect auxin-dependent root growth, lateral root formation, and timing of gravitropism, indicating that SHY2/IAA3 regulates multiple auxin responses in roots. The phenotypes suggest that SHY2/IAA3 may activate some auxin responses and repress others. Models invoking tissue-specificity, feedback regulation, or control of auxin transport may explain these results.

Comparison of the efficacy of dihydropyridine calcium channel blockers in African American patients with hypertension. ISHIB Investigators Group. International Society on Hypertension in Blacks.

BACKGROUND: Hypertension is a prevalent disease among African Americans, and successful treatment rates are low. Since calcium channel blockers are well-tolerated and efficacious in African Americans, we undertook this study to compare the efficacy, safety, and tolerability of 3 commonly prescribed calcium channel blockers: amlodipine besylate (Norvasc), nifedipine coat core (CC) (Adalat CC), and nifedipine gastrointestinal therapeutic system (GITS) (Procardia XL). METHODS: One hundred ninety-two hypertensive patients across 10 study centers were randomly assigned to double-blind monotherapy with amlodipine besylate (5 mg/d), nifedipine CC (30 mg/d), or nifedipine GITS (30 mg/d) for 8 weeks. Patients not achieving therapeutic response after 4 weeks had their dose doubled for the next 4 weeks. The primary end point was a comparison of the average reduction (week 8 minus baseline) in 24-hour ambulatory diastolic blood pressure (DBP). Secondary end points included a comparison of average 24-hour ambulatory systolic blood pressure (SBP), office SBP or DBP reduction, responder rates, safety, and tolerability. RESULTS: One hundred sixty-three patients were evaluable for efficacy after 8 weeks. There was no significant difference in the average 24-hour ambulatory DBP (-8.5, -9.0, and -6.1 mm Hg, respectively) or SBP (-14.3, -15.7, and -11.8 mm Hg, respectively) reduction. Average office SBP and DBP were reduced to a comparable degree (19-22 mm Hg [P =.50] and 12-14 mm Hg [P =.51], respectively). Responder rates (DBP <90 or reduced by > or = 10 mm Hg) were similar (P = .38). Discontinuation rates and adverse event frequency were distributed similarly across the 3 treatment groups. CONCLUSION: The efficacy, safety, and tolerability of the 3 dihydropyridine calcium channel blockers are equivalent in African Americans with stages 1 and 2 hypertension.