Characterization of Leaf Rust and Stripe Rust Resistance in Spring Wheat 'Chilero'.

Since 1984, the 'Chilero' spring wheat line developed by CIMMYT has proven to be highly resistant to leaf rust and stripe rust. Amid efforts to understand the basis of resistance of this line, a recombinant inbred line (RIL) population derived from a cross between Avocet and Chilero was studied. The parents and RILs were characterized in field trials for leaf rust and stripe rust in three locations in Mexico between 2012 and 2015 and genotyped with DArT-array, DArT-GBS, and SSR markers. A total of 6,168 polymorphic markers were used to construct genetic linkage maps. Inclusive composite interval mapping detected four colocated resistance loci to both rust diseases and two stripe rust resistant loci in the Avocet × Chilero population. Among these, the quantitative trait locus (QTL) on chromosome 1BL was identified as a pleotropic adult plant resistance gene Lr46/Yr29, whereas QLr.cim-5DS/QYr.cim-5DS was a newly discovered colocated resistance locus to both rust diseases in Chilero. Additionally, one new stripe rust resistance locus on chromosome 7BL was mapped in the current population. Avocet also contributed two minor colocated resistance QTLs situated on chromosomes 1DL and 4BS. The flanking SNP markers can be converted to breeder friendly Kompetitive Allele Specific PCR (KASP) markers for wheat breeding programs.

Direct introgression of untapped diversity into elite wheat lines.

The effective utilization of natural variation has become essential in addressing the challenges that climate change and population growth pose to global food security. Currently adopted protracted approaches to introgress exotic alleles into elite cultivars need substantial transformation. Here, through a strategic three-way crossing scheme among diverse exotics and the best historical elites (exotic/elite1//elite2), 2,867 pre-breeding lines were developed, genotyped and screened for multiple agronomic traits in four mega-environments. A meta-genome-wide association study, selective sweeps and haplotype-block-based analyses unveiled selection footprints in the genomes of pre-breeding lines as well as exotic-specific associations with agronomic traits. A simulation with a neutrality assumption demonstrated that many pre-breeding lines had significant exotic contributions despite substantial selection bias towards elite genomes. National breeding programmes worldwide have adopted 95 lines for germplasm enhancement, and 7 additional lines are being advanced in varietal release trials. This study presents a great leap forwards in the mobilization of GenBank variation to the breeding pipelines.

[siRNAs with high specificity to the target: a systematic design by CRM algorithm].

'Off-target' silencing effect hinders the development of siRNA-based therapeutic and research applications. Common solution to this problem is an employment of the BLAST that may miss significant alignments or an exhaustive Smith-Waterman algorithm that is very time-consuming. We have developed a Comprehensive Redundancy Minimizer (CRM) approach for mapping all unique sequences ("targets") 9-to-15 nt in size within large sets of sequences (e.g. transcriptomes). CRM outputs a list of potential siRNA candidates for every transcript of the particular species. These candidates could be further analyzed by traditional "set-of-rules" types of siRNA designing tools. For human, 91% of transcripts are covered by candidate siRNAs with kernel targets of N = 15. We tested our approach on the collection of previously described experimentally assessed siRNAs and found that the correlation between efficacy and presence in CRM-approved set is significant (r = 0.215, p-value = 0.0001). An interactive database that contains a precompiled set of all human siRNA candidates with minimized redundancy is available at http://129.174.194.243. Application of the CRM-based filtering minimizes potential "off-target" silencing effects and could improve routine siRNA applications.

Salutary effects of exogenous adenosine administration on in vivo myocardial stunning.

Augmentation of endogenous adenosine levels is associated with decreased myocardial ischemic-reperfusion injury. The purpose of this study was to determine whether exogenous adenosine administered before ischemia could attenuate postischemic myocardial dysfunction. Regional myocardial stunning was induced by 15 minutes of coronary artery occlusion and 90 minutes of reperfusion in an open-chest canine preparation. Regional ventricular function was assessed by measurement of systolic wall thickening. Control untreated hearts were compared with two groups of hearts treated immediately before ischemia with intracoronary adenosine (5 micrograms/kg per minute and 50 micrograms/kg per minute). A fourth group of hearts was treated for the first 30 minutes of reperfusion with adenosine (50 micrograms/kg per minute). Preischemic adenosine administration increased coronary flow sixfold to sevenfold without altering regional function, mean arterial pressure, or left ventricular end-diastolic pressure. Both adenosine pre-treatments attenuated stunning compared with results in control animals (14.7% +/- 5.1% and 21.6% +/- 7.3% of preischemic systolic wall thickness versus -14.0% +/- 10%). Adenosine treatment during reperfusion transiently increased function in parallel with increased coronary blood flow, but after termination of the infusion regional function was not different from that in control stunned hearts (-5.0% +/- 13.1% of preischemic systemic wall thickness). These results indicate that adenosine pretreatment is associated with attenuation of stunning, an effect that can be produced at doses that do not alter systemic hemodynamics.

Spectrofluorimetric analysis and buccal absorption of medifoxamine.

Medifoxamine is a new investigational antidepressant drug. Its buccal absorption at pH 5-9, which can be considered as an in-vivo model of passive drug transfer through a lipid membrane, was studied in six normal, healthy volunteers to predict its pharmacokinetic profile in man. Maximum absorption of medifoxamine occurred at pH 8, which is close to its pKa (8.5).

Buccal absorption of drugs: an in vivo measurement of their innate lipophilicity.

The area under the curve of the buccal absorption of drugs against pH (AUC) is significantly correlated with their pH-dependent renal excretion, and protein binding. Therefore, AUC may be considered as an in vivo model for the quantitative measurement of innate lipophilicity and passage of drugs across lipid membranes.

A prospective study to investigate the relationship between periodontal disease and adverse pregnancy outcome.

OBJECTIVE: This study aimed to investigate a relationship between maternal periodontal disease and preterm birth, low birth weight and late miscarriage. DESIGN: Prospective study in a single centre. SETTING: Guy's and St Thomas' Hospital Trust, London, UK between August 1998 and July 2001. SUBJECTS AND METHODS: Pregnant women were recruited on attending an ultrasound scan at approximately 12 weeks of pregnancy. Subjects completed a questionnaire and underwent periodontal examination. MAIN OUTCOME MEASURES: Plaque and bleeding scores, pocket probing depth and loss of attachment. Pregnancy outcome data was collected retrospectively, including gestational age and birth weight at delivery. RESULTS: Data were collected for 3,738 subjects. Regression analysis indicated that there were no significant relationships between the severity of periodontal disease and either preterm birth (PTB) or low birth weight (LBW). In contrast, there did appear to be a correlation between poorer periodontal health and those that experienced a late miscarriage. CONCLUSIONS: There was no association between either preterm birth or low birth weight and periodontal disease in this population. There is evidence of a correlation between markers of poorer periodontal health and late miscarriage.

Pattern of adolescent growth among the Brahmin girls--rural-urban variation.

A cross-sectional study of adolescent growth was undertaken among the Brahmin girls residing in rural and urban areas of Sagar districts, Madhya Pradesh to evaluate the urban-rural differences. Six anthropometric measurements, such as weight, stature, sitting height, head circumference, upper arm circumference and chest girth are taken into consideration. Though the urban girls show consistently higher values of weight, stature, sitting height and chest girth than the rural girls, but in case of head circumference and upper arm circumference they show consistently lower values. The maximum increment occurs between the ages 13 and 14 years in all the six measurements in both rural and urban girls.

Immunomodulatory studies of a bioactive fraction from the fruit of Prunus cerasus in BALB/c mice.

In order to evaluate the role of ethyl acetate fraction (PNRS-EtOAC) obtained from the Prunus cerasus fruit in the modulation of immune responses, detailed studies were carried out using a panel of in vivo assays. Oral administration of PNRS-EtOAC (25-100 mg/kg) stimulated the IgM and IgG titre expressed in the form of hemagglutination antibody (HA) titre. Further, it elicited a dose related increase in the delayed type hypersensitivity reaction (DTH) after 24 and 48 h in BALB/c mice. Besides augmenting the humoral and cell mediated immune response, the concentration of cytokines (IFN-γ, IL-4, and TNF-α) in serum with respect to T cell interactions, i.e. the proliferation of lymphocytes were significantly increased at 50 mg/kg compared with the control. The results in these studies demonstrated the immunostimulatory effect of PNRS-EtOAC in a dose-dependent manner with respect to the macrophage activation possibly expressing the phagocytosis and nitrite production by the enhancement of TNF-α production as a mode of action.

Bioavailability of calcium, iron and zinc fortified whole wheat flour chapatti.

The bioavailability and interactive effects of calcium, iron and zinc fortified whole wheat flour chapattis on female Sprague-Dawley albino rats were determined. The whole wheat flour was fortified with CaCO3, FeSO4 and ZnSO4 at 1000, 40 and 20 mg/kg, respectively and fed to 64 female Sprague-Dawley rats for 4 weeks. Retention of Ca, Fe and Zn was determined in plasma, femur and liver tissues. Ca levels in plasma and liver did not alter significantly while the Ca retention in femur changed significantly with the change in fortificants. The calcium retention was higher in the femur of rats fed on the diet supplemented with Ca + Zn (221 +/- 13.61 mg/g) than the rats fed on the diet supplemented with Ca + Fe (219 +/- 18.92 mg/g). The iron in plasma, liver and femur ranged from 2.19 +/- 0.11 to 2.77 +/- 0.10 microg/ml, 203.5 +/- 13.24 to 251.5 +/- 17.19 microg/g and 43.5 +/- 1.05 to 52 +/- 2.07 microg/g while zinc content ranged from 1.31 +/- 0.089 to 1.55 +/- 0.114 microg/ml, 89.5 +/- 3.41 to 132 +/- 6.10 microg/g and 175 +/- 8.29 to 191 +/- 10.85 microg/g, respectively. The minerals interacted with each other resulting in decrease of bioavailability among each other. The absorption was higher in the rats fed on fortified diet than those fed on unfortified chapatti diet. Hence, it is concluded that fortification of whole wheat flour is feasible to overcome the Ca, Fe and Zn malnutrition in the vulnerable groups.

A case-control study to investigate an association between adverse pregnancy outcome and periodontal disease.

OBJECTIVES: The aim of this case-control study was to ascertain if women who experienced a preterm (or premature) birth had any differences in periodontal disease severity compared with women who delivered at term. MATERIAL AND METHODS: Subjects were recruited postpartum. Case subjects delivered a baby before 37 weeks of gestation whereas control subjects gave birth at or around term. A questionnaire was administered by a Research Midwife, designed to collect demographic information, pregnancy outcome variables and information on other factors which may influence health in pregnancy. A periodontal examination was then performed at the bedside. RESULTS: Demographic variables were similar between case and control subjects. There was a higher proportion of case subjects who reported smoking. There were no differences in oral hygiene, bleeding on probing or loss of attachment; however, control subjects had a higher proportion of periodontal pockets probing 5 mm or greater. CONCLUSIONS: There was no association between the severity of periodontal disease and pregnancy outcome in this population.

Seat belt aorta.

This review of 11 cases of seat-belt associated blunt abdominal aortic trauma, includes nine cases reported in the literature and two new cases. Lap-type seat belts were the cause of this injury in eight of the 11 patients (73%). Clinical presentation was acute in 73% of the cases, with symptoms of acute arterial insufficiency, or an acute abdomen or neurologic deficits. Chronic manifestations, such as, persistent abdominal pain, claudication, abdominal mass with a bruit and decreased distal pulses, presented as late as nine months after the injury occurred. The mechanism producing the injury is discussed and a classification system for the different types of abdominal aortic injuries is put forth. Circumferential intimal disruption was the most common aortic defect. The majority of these were located distal to the inferior mesenteric artery. Diagnosis involves a high degree of suspicion in a victim wearing a seat belt with neurologic deficits, signs of acute arterial insufficiency, or a pulsatile abdominal mass. The mortality rate was 18% (2/11 patients), and occurred in patients wearing lap belts. Overall outcome depends on prompt recognition followed by appropriate surgical intervention.

Improvement of symptoms in infant colic following reduction of lactose load with lactase.

Transient lactose intolerance has been identified as a possible causative factor in infant colic. A double-blind randomised placebo-controlled crossover study to investigate this has been undertaken in 53 babies with symptoms of colic. Pre-incubation of the feed with lactase resulted in breath hydrogen levels and total crying time which were both at least 45% lower than figures with placebo treatment, in 26% of the full trial group (95% confidence interval 12.9% to 44.4%), and in 38% of compliers (95% confidence interval 18.8% to 59.4%). The remainder did not respond to the same extent. These findings suggest that infant colic may have a multiple aetiology, and that in a significant number of cases the immediate cause is transient lactose intolerance, in which cases pretreatment of feeds with lactase can result in considerable symptomatic benefits.

Adenosine and the stunned heart.

Adenosine is one agent under investigation as a therapeutic intervention of myocardial stunning. Adenosine caused numerous effects on the cardiovascular system through its interaction with A1 and A2 receptors. We investigated adenosine A1 receptor mediated mechanisms of cardiac protection in the stunned rat myocardium. Previous studies showed that both adenosine and R-phenylisopropyladenosine (PIA), an A1 receptor agonist, prolonged the time to onset of ischemic contracture in ischemic isolated rat hearts. Phenylaminoadenosine, an A2 receptor agonist, did not have any effect, while receptor antagonists blocked adenosine and PIA action. Direct attenuation of the effects of myocardial stunning was observed by altering levels of interstitial fluid adenosine. Our laboratory has shown that administration of erythro-9(2-hydroxy-3-nonyl) adenine (EHNA; an adenosine deaminase inhibitor) to dogs subjected to left anterior descending coronary artery (LAD) occlusion followed by reperfusion results in dramatic increases in ischemic levels of interstitial fluid adenosine and postischemic myocardial function. Using a similar model in dogs, we have shown that exogenous intracoronary adenosine (50 micrograms/kg per min) augmented postischemic recovery of function, as assessed by significant enhancement (p < 0.01) of systolic wall thickness (7.0 +/- 3.0 pretreatment vs -5.7 +/- 1.7 controls). These data support the role for an adenosine A1 receptor mediated mechanism for protection against myocardial stunning.

Extracorporeal enzymatic heparin removal: use in a sheep dialysis model.

Extracorporeal medical devices such as the hemodialyzer rely on systemic heparinization to prevent thrombus formation. Heparin, however, can lead to serious hemorrhagic complications. A blood filter containing immobilized heparinase, a heparin specific enzyme, was used to degrade heparin into small fragments which have significantly less anticoagulant activity than the parent compound. The heparinase filter was tested in the extracorporeal circuit during the hemodialysis of adult sheep. At a blood flow of 200 ml/min, the clearance of heparin varied from 50 to 70 ml/min (N = 16) depending on the amount of immobilized heparinase in the filter. Hemolysis was insignificant as measured by the animals' red cell counts, hematocrit, total hemoglobin and a plasma-free hemoglobin value of 89 +/- 33 mg/dl (N = 16) (less than 1% of the total hemoglobin). The white cell counts dropped to 47 +/- 7% (N = 16) of the initial value at 20 minutes and rebounded to 72 +/- 10% (N = 16) after one hour. The platelet counts decreased to 55 +/- 8% (N = 16) of the initial value after one hour. No change in heparin clearance was observed when reactors were used repeatedly in adult sheep over a 10 week period. The red cell counts, white cell counts, platelet counts, total hemoglobin and hematocrit did not change after 10 weeks of exposure to the device. These results suggest that with further study, heparinase may be useful in removing heparin used to anticoagulate blood in extracorporeal circuits.

Henderson-Hasselbalch equation is inadequate for the measurement of transmembrane diffusion of drugs and buccal drug absorption is a useful alternative.

1. The transmembrane diffusion of weakly acidic or basic drugs is being commonly assessed from their degree of ionization or ratio unionized/ionized forms (ratio U/I) as calculated from Henderson-Hasselbalch equation (HHEq). 2. Buccal drug absorption (BA) at pH 5-9 has been proposed as an in vivo model for passage of drugs across lipid membranes. 3. Area under the curve (AUC) of BA against pH 5-9 of 18 basic drugs has been reported to be significantly related to their pH dependent renal excretion. 4. We have calculated, using HHEq, ratios U/I of 10 weak bases at pH 5-9 and 10 weak acids at pH 4-8, whose percentage BA at these pH levels was available in the literature. 5. These ratios were not related to their %BA at corresponding pH levels. 6. Therefore it is proposed that HHEq is inadequate in the anticipation of transmembrane diffusion of drugs and AUC of %BA of drugs at pH 4-9 is a useful alternative.

Effects of adenosine and acadesine on interstitial nucleosides and myocardial stunning in the pig.

5-Amino-4-imidazolecarboxamide riboside (AICAr) or acadesine has been proposed to exert cardioprotection by enhancing adenosine production in ischemic myocardium. However, there are conflicting reports on acadesine's effects in ischemic myocardium and few studies in which myocardial adenosine levels have been measured. The purpose of this study was to determine whether acadesine increases interstitial fluid adenosine levels and attenuates myocardial stunning or potentiates the effects of adenosine in the intact pig. In pentobarbital-anesthetized pigs, myocardial stunning was induced by 10 min left anterior descending coronary artery occlusion and 90 min reperfusion. Regional ventricular function was assessed by measuring systolic wall thickening, and interstitial nucleosides were estimated by cardiac microdialysis. Control hearts were compared with hearts treated with acadesine, adenosine, and adenosine plus acadesine. Adenosine pretreatment (100 microg x kg(-1) x min(-1), intracoronary) immediately prior to ischemia increased interstitial adenosine levels 9-fold and improved postischemic functional recovery from a control value of 17.6 +/- 4.1% to 43.6 +/- 3.4% of preischemic systolic wall thickening. In contrast, acadesine (20 mg/kg i.v. bolus 10 min prior to ischemia + 0.5 mg x kg (-1) x min(-1), i.v. infusion through 60 min reperfusion) had no effect on interstitial fluid adenosine levels or the recovery of regional function (21.5 +/- 5.9% recovery), nor were the functional effects of adenosine potentiated by acadesine. These findings indicate that acadesine does not enhance myocardial adenosine levels, attenuate myocardial stunning, or potentiate the cardioprotective effects of adenosine in the pig.

An investigation into the association among preterm birth, cytokine gene polymorphisms and periodontal disease.

OBJECTIVE: To investigate a putative relationship between preterm delivery and the carriage of polymorphic genes that code for the cytokines interleukin-1beta (IL-1beta) at codon +3953 and tumour necrosis factor-alpha (TNF-alpha) at codon -308 in a group of postpartum women and to elucidate if the concurrent presence of periodontal disease increased the risk of preterm delivery in this group. DESIGN: Case-control study SETTING: Postnatal wards at Guy's and St Thomas' Hospital Trust. POPULATION: Postpartum women from southeast London, UK. METHODS: Case subjects were defined as those who experienced a birth at less than 37 weeks of gestation. Control subjects gave birth at term. Demographic data were collected and a periodontal examination was performed. Blood samples were collected and analysed by restriction fragment length polymerase techniques for the presence of each of the allelic variants. MAIN OUTCOME MEASURES: The level of periodontal disease and the carriage of allelic variants of IL-1beta+3953 and TNF-alpha-308 genes. RESULTS: Forty-eight case subjects and 82 control subjects were assessed. There was no statistically significant difference in the carriage of the IL-1beta+3953 allelic variant between cases and controls (29%versus 18%, P= 0.112). However, 23 (48%) of the case subjects and 24 (29%) of controls were heterozygous or homozygous for the variant TNF-alpha-308 gene (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.0-5.0, P= 0.026). There was no association between the carriage of either the polymorphic IL-1beta+3953 or TNF-alpha-308 variant and the severity of periodontal disease. The combination of periodontal disease and the allelic variant did not increase the risk of preterm delivery. CONCLUSIONS: In this study, a higher proportion of women who delivered preterm carried the polymorphic TNF-alpha-308 gene. There did not appear to be any interaction between either of the genotypes and periodontal disease with preterm delivery as has been reported for bacterial vaginosis and the TNF-alpha-308 polymorphic gene.