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Genetic regions in the rice genome are identified that affect the proportion of grains that remain intact after milling (the head rice yield) and the degree of chalkiness in the grain., Higher head rice yield (HRY), which represents the proportion of intact grains that survive milling, and lower grain chalkiness (opacity) are key quality traits. We investigated the genetic basis of HRY and chalkiness in 320 diverse resequenced accessions of indica rice with integrated single- and multi-locus genome-wide association studies using 2.26 million single-nucleotide polymorphisms. We identified novel haplotypes that underly higher HRY on chromosomes 3, 6, 8, and 11, and that lower grain chalkiness in a fine-mapped region on chromosome 5. Whole-genome sequencing of 92 IRRI breeding lines was performed to identify the genetic variants of HRY and chalkiness. Rare and novel haplotypes were found for lowering chalkiness, but missing alleles hindered progress towards enhancing HRY in breeding material. The novel haplotypes that we identified have potential use in breeding programs aimed at improving these important traits in the rice crop.

In recent years, an increasing number of inhabitants of Central America have developed a form of chronic kidney disease, now named Mesoamerican nephropathy. This disease is characterized by minimal proteinuria, hyperuricemia, hypokalemia and reduced glomerular filtration rate. Histologically the kidneys manifest tubulointerstitial nephritis. The cause(s) of this disease remain unknown. Some have proposed that dehydration, in combination with hyperuricemia, may be primarily responsible for Mesoamerican nephropathy. In this article, I propose the hypothesis that the disease may be largely due to rehydration with large amounts of contaminated water, whereas dehydration would play only a contributing role.

To ensure rice food security, the target outputs of future rice breeding programmes should focus on developing climate-resilient rice varieties with emphasis on increased head rice yield coupled with superior grain quality. This challenge is made greater by a world that is increasingly becoming warmer. Such environmental changes dramatically impact head rice and milling yield as well as increasing chalkiness because of impairment in starch accumulation and other storage biosynthetic pathways in the grain. This review highlights the knowledge gained through gene discovery via quantitative trait locus (QTL) cloning and structural-functional genomic strategies to reduce chalk, increase head rice yield, and develop stable lines with optimum grain quality in challenging environments. The newly discovered genes and the knowledge gained on the influence of specific alleles related to stability of grain quality attributes provide a robust platform for marker-assisted selection in breeding to design heat-tolerant rice varieties with superior grain quality. Using the chalkiness trait in rice as a case study, we demonstrate here that the emerging field of systems genetics can help fast-track the identification of novel alleles and gene targets that can be pyramided for the development of environmentally robust rice varieties that possess improved grain quality.

The inactivation of starch branching IIb (SBEIIb) in rice is traditionally associated with elevated apparent amylose content, increased peak gelatinization temperature, and a decreased proportion of short amylopectin branches. To elucidate further the structural and functional role of this enzyme, the phenotypic effects of down-regulating SBEIIb expression in rice endosperm were characterized by artificial microRNA (amiRNA) and hairpin RNA (hp-RNA) gene silencing. The results showed that RNA silencing of SBEIIb expression in rice grains did not affect the expression of other major isoforms of starch branching enzymes or starch synthases. Structural analyses of debranched starch showed that the doubling of apparent amylose content was not due to an increase in the relative proportion of amylose chains but instead was due to significantly elevated levels of long amylopectin and intermediate chains. Rices altered by the amiRNA technique produced a more extreme starch phenotype than those modified using the hp-RNA technique, with a greater increase in the proportion of long amylopectin and intermediate chains. The more pronounced starch structural modifications produced in the amiRNA lines led to more severe alterations in starch granule morphology and crystallinity as well as digestibility of freshly cooked grains. The potential role of attenuating SBEIIb expression in generating starch with elevated levels of resistant starch and lower glycaemic index is discussed.

The contribution of angiotensin-(1-7) [Ang-(1-7)] to the antihypertensive actions of omapatrilat, a novel vasopeptidase inhibitor, was evaluated in 22 salt-sensitive, low renin, hypertensive subjects as a substudy of a multicenter randomized, double-blind, parallel study of 4 weeks duration. A total of 25 other subjects received lisinopril as the active control. Omapatrilat (40 mg) produced sustained control of blood pressure (BP) (as assessed by 24-h ambulatory BP measurements) that was significantly greater than that produced by 20 mg daily of lisinopril. The antihypertensive response to either drug was accompanied by similar sustained inhibition of angiotensin converting enzyme activity. Plasma levels of angiotensin I (Ang I), angiotensin II (Ang II) and Ang-(1-7) were not altered by treatment with either omapatrilat or lisinopril, even though both regimens produced a modest rise in plasma renin activity. In contrast, urinary excretion rates of Ang I and Ang-(1-7) but not Ang II increased significantly throughout the dosing period of subjects who were given omapatrilat, whereas the smaller antihypertensive response produced by lisinopril had a smaller and transient effect on increasing urinary excretion rates of Ang-(1-7). Omapatrilat, being a single molecule inhibiting neutral endopeptidase and converting enzyme simultaneously, controlled salt-sensitive hypertension by a mechanism that was associated with sustained increases in urinary Ang-(1-7) excretion. We suggest that Ang-(1-7) may be a component of the mechanisms by which omapatrilat induces an antihypertensive response in salt sensitive hypertension.

Previously, we have shown that an acute injury to the kidney produced by an intrarenal injection of phenol causes an immediate increase in blood pressure and in norepinephrine (NE) secretion from the posterior hypothalamus. The studies suggest that in this model afferent impulses from the kidney to central integrative structures in the brain may be responsible for the increase in blood pressure. To further evaluate whether a renal injury caused by the intrarenal injection of phenol leads to a permanent elevation of blood pressure and whether this is mediated by increased sympathetic nervous system activity, we examined the chronic effects (4 weeks) of an intrarenal injection of 50 microL of 10% phenol on blood pressure and NE secretion from the posterior hypothalamus. Systolic blood pressure increased from 128 +/- 2.1 to 176 +/- 1.5 mm Hg (P.01) 4 weeks after receiving the intrarenal injection of phenol, but it did not change in rats that received the vehicle (128 +/- 2.4 and 135 +/- 1.7 mm Hg) and in rats that were subjected to renal denervation (127 +/- 3.4 and 124 +/- 1.0 mm Hg). The secretion of NE from the posterior hypothalamic nuclei was greater (P.01) in rats that received phenol (253 +/- 9.6 pg/mL) than in controls (158 +/- 8.6 pg/mL) and denervated rats (170 +/- 2.1 pg/mL). These studies have shown that a limited injury to one kidney may cause a permanent elevation of blood pressure and this is associated with increased sympathetic nervous system activity.

Hyperinsulinemia, insulin resistance, or both have been described in a proportion of patients with essential hypertension, and also are considered a risk for atherosclerotic cardiovascular disease. In this study, we have examined whether salt sensitivity and hyperinsulinemia are associated in patients with essential hypertension. We have measured blood insulin and glucose response to an acute oral glucose load in a group of hypertensive patients, classified according to their salt sensitivity. To determine salt sensitivity, patients received a diet containing a low (20 mEq/day) Na+ intake for 1 week followed by a high (250 mEq/day) Na+ intake for 1 week more. Twenty-nine patients were classified as salt sensitive, and 23 as salt resistant. Baseline plasma glucose and insulin were not different between salt-sensitive and salt-resistant patients. Following an oral glucose load, the area-under-the curve of glucose was greater (P < .05) in salt-sensitive than in salt-resistant hypertensive patients (900 +/- 26.4 and 810 +/- 29.1 mmol/L x 2 h, respectively). The area-under-the curve of insulin was greater (P < .01) in salt-sensitive (52,664 +/- 3,666 pmol/L x 2 h) than in salt-resistant patients (37,977 +/- 3,300 pmol/L x 2 h). A direct correlation was present between insulin area-under-the curve and salt sensitivity (r = 0.26), but did not reach statistical significance (P < .06). Salt-sensitive patients manifested increased serum levels of total cholesterol, LDL-cholesterol and increased urinary albumin excretion when compared with salt-resistant patients. In conclusion, these studies have demonstrated that in response to an oral glucose load, salt-sensitive patients with essential hypertension manifest increased insulin secretion. The studies have confirmed the presence of increased urinary albumin excretion and serum levels of atherogenic lipoproteins in salt-sensitive compared with salt-resistant patients. In salt-sensitive hypertensive patients, hyperinsulinemia, hyperlipidemia and microalbuminuria form a cluster with possible atherogenic potential. Salt sensitivity can be a marker for increased cardiovascular risk in patients with essential hypertension.

Microalbuminuria has been shown in approximately 40% of patients with essential hypertension. Previous studies have failed to demonstrate any consistent relationship between microalbuminuria and levels of office blood pressure. Because average ambulatory blood pressure correlates with incidence of cardiovascular morbidity and mortality better than office blood pressure, we have studied whether levels of urinary albumin excretion correlate with average diurnal, nocturnal, or 24-h blood pressure better than with office blood pressure. Sixty-three patients with essential hypertension and 21 healthy volunteers were included in the study. Twenty-four hypertensive patients failed to show the normal nighttime fall in blood pressure of at least 10/5 mm Hg and were defined as "nondippers"; the remaining were defined as "dippers." Office blood pressure was not different between dippers and nondippers. However, nighttime systolic and diastolic blood pressures were significantly greater in nondippers than in dippers. The median urinary albumin excretion in nondippers (42 mg/24 h) was significantly greater (P < .001) than in dippers (17.5 mg/24 h), and in normal subjects (8.6 mg/24 h). A significant correlation was present between nighttime systolic and diastolic blood pressure and urinary albumin excretion (UAE) and between 24-h systolic blood pressure and UAE in all hypertensive patients; in addition, a significant correlation was present between 24-h diastolic and nighttime diastolic blood pressure and UAE in nondippers. The increased amount of UAE in nondipper hypertensive patients suggests the presence of greater renal damage than in dippers.

High dietary Na+ raises mean arterial pressure (MAP) by more than 10% in salt-sensitive (SS) patients with essential hypertension. To test whether the rise in MAP in these patients is caused by a Na(+)-linked increase in [Ca2+]i in vascular smooth muscle cells, we measured [Ca2+]i in the lymphocytes of 14 patients with essential hypertension kept on a Na+ intake of 20 mEq/day for 9 days, and 200-mEq/day for 14 days. Nifedipine gastrointestinal transport system (GITS) (30 mg/day) was given during the last 4 days of each diet. We isolated lymphocytes on Ficoll-Hypaque gradient and measured [Ca2+]i levels using Fura-2 fluorescent dye. During low Na+ intake, there was no difference in MAP (102 +/- 3.5 v 93 +/- 3.8 mm Hg) and in lymphocytes [Ca2+]i (80 +/- 3.0 v 87 +/- 5.4 nmol/L) between the seven salt-sensitive and the seven salt-resistant patients. During high Na+ intake, MAP (92 +/- 2.8 mm Hg) and [Ca2+]i (85 +/- 6.8 nmol/L) did not change in salt-resistant patients. On the contrary, MAP (115 +/- 3.4 mm Hg) and [Ca2+]i (130 +/- 11.1 nmol/L) increased significantly (P less than .01) in the salt-sensitive patients. Nifedipine did not significantly alter MAP and [Ca2+]i in both groups of patients during low Na+ and in salt-resistant patients during high Na+ intake. On the contrary, during high Na+ intake, nifedipine decreased significantly (P less than .01) both MAP (104 +/- 2.4 mm Hg) and [Ca2+]i (89 +/- 5.7 nmol/L) in salt-sensitive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Several patients with essential hypertension manifest an abnormal (greater than 30 mg/24 h) urinary albumin excretion (UAE). Since microalbuminuria is considered an independent predictor of cardiovascular morbidity and mortality, studies are currently being undertaken to determine the effect of various antihypertensive agents on UAE, on the assumption that a reduction of UAE might result in improved prognosis in patients with essential hypertension. Twenty-four patients with essential hypertension were randomly divided into two groups of 12. The first group received 20 mg/day enalapril for 8 weeks, followed by 20 to 40 mg/day nitrendipine for 8 more weeks. The second group received nitrendipine for 8 weeks, followed by enalapril. Mean arterial pressure decreased similarly during both therapeutic regimens in the two groups of patients. In patients of group 1, UAE decreased significantly (P less than .01) from 74 +/- 7.0 to 33 +/- 5.8 mg/24 h after 8 weeks of treatment with enalapril; during the following 8 weeks of treatment with nitrendipine, UAE increased to 58 +/- 5.3 mg/24 h (P less than .02). In patients of group 2, UAE did not change during the first 8 weeks of therapy with nitrendipine despite a significant reduction in blood pressure; subsequently, after 8 weeks of therapy with enalapril, UAE decreased from 62 +/- 9.2 to 31 +/- 4.8 mg/24 h (P less than .01). This study demonstrates that enalapril but not nitrendipine may reduce UAE in patients with essential hypertension despite similar antihypertensive efficacy. The significance of microalbuminuria and the impact of the normalization of UAE on cardiovascular morbidity and mortality in patients with essential hypertension remains to be determined.