The Evolution of HD2 Proteins in Green Plants.

In eukaryotes, protein deacetylation is carried out by two well-conserved histone deacetylase (HDAC) families: RPD3/HDA1 and SIR2. Intriguingly, model plants such as Arabidopsis express an additional plant-specific HDAC family, termed type-2 HDACs (HD2s). Transcriptomic analyses from more than 1300 green plants generated by the 1000 plants (1KP) consortium showed that HD2s appeared early in green plant evolution, the first members being detected in several streptophyte green alga. The HD2 family has expanded via several rounds of successive duplication; members are expressed in all major green plant clades. Interestingly, angiosperm species express new HD2 genes devoid of a zinc-finger domain, one of the main structural features of HD2s. These variants may have been associated with the origin and/or the biology of the ovule/seed.

Eastern Canadian Colorectal Cancer Consensus Conference: standards of care for the treatment of patients with rectal, pancreatic, and gastrointestinal stromal tumours and pancreatic neuroendocrine tumours.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Halifax, Nova Scotia, October 20-22, 2011. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of rectal cancer, including pathology reporting, neoadjuvant systemic and radiation therapy, surgical techniques, and palliative care of rectal cancer patients. Other topics discussed include multidisciplinary cancer conferences, treatment of gastrointestinal stromal tumours and pancreatic neuroendocrine tumours, the use of folfirinox in pancreatic cancer, and treatment of stage ii colon cancer.

Eastern Canadian colorectal cancer consensus conference: application of new modalities of staging and treatment of gastrointestinal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Ottawa, Ontario, October 22-23, 2010. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer, such as the use of epidermal growth factor inhibitors in metastatic colon cancer, the benefit of calcium and magnesium with oxaliplatin chemotherapy, the role of microsatellites in treatment decisions for stage II colon cancer, the staging and treatment of rectal cancer, and the management of colorectal and metastatic pancreatic cancers.

Maternal resveratrol treatment during pregnancy improves adverse fetal outcomes in a rat model of severe hypoxia.

Prenatal hypoxia is a common complication in pregnancy. We sought to determine whether resveratrol, a phytoalexin shown to improve health in several species, improves fetal outcomes associated with prenatal hypoxia in rats. Supplementation of maternal diets with resveratrol (4 g/kg diet) from gestational day (GD) 7 to GD21 almost completely reversed fetal demise in hypoxic (8.5% oxygen) pregnancies. We also show that resveratrol crosses the placenta, and may affect the fetus directly.

Sedentariness and increased visceral adiposity in adult perinatally iron-deficient rats.

BACKGROUND: Perinatal iron deficiency (PID) adversely programs offspring resulting in alterations in adult cardiometabolic function. Increased visceral adiposity is the proposed culprit for these sequelae, and may be potentiated by decreased physical activity. Herein, we determined (i) the effect of PID on visceral adipose tissue (VAT) and locomotor activity, and (ii) whether increased VAT is associated with blood pressure responsiveness to increased dietary sodium. METHODS AND RESULTS: Dams were fed a low iron diet (<10 mg/kg Fe) prior to and throughout gestation. From 12 to 35 weeks of age, locomotor activity (assessed by radiotelemetry) in PID offspring was 25% lower compared with control offspring (P<0.001). At 36 weeks of age, PID offspring had 15% more VAT than controls (P<0.05). Furthermore, the elevation of mean arterial pressure (by radiotelemetry) in response to increased sodium intake was approximately twofold greater in the PID offspring (P<0.05). CONCLUSIONS: PID results in increased visceral adiposity, which was associated with enhanced blood pressure responsiveness to dietary salt, perhaps due to programmed sedentary behavior.

Reliability of information collected by proxy in family studies of Alzheimer's disease.

The study evaluated the reliability of data obtained from proxy informants. The index subjects in this study were 81 nondemented participants in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) study. These index subjects and 159 proxy informants, identified by the index subjects, participated in the study. The kappa statistic with multiple raters per subject (for dichotomous variables) and the intraclass correlation coefficient (for continuous variables) were used to measure reliability. Among proxy respondents who provided answers, there was excellent agreement between proxy responses and the responses of the index subjects (0.7 < or = kappa < or =0.9), with the exception of questions about head injury (kappa = 0.4). A large proportion (>90%) of the proxy informants in this study were able to provide information on most items. Higher nonresponse rates (as high as 30%) were observed for medication history and women's health questions. This study supports the reliability of proxy responses for most categories of questions that are elicited in typical epidemiological studies, including the MIRAGE study.

Moderate intensity exercise training improves cardiorespiratory fitness in women.

Among women, there is an increased prevalence of sedentary lifestyle and less participation in physical activity at levels recommended by the Surgeon General. As a result, women have been identified as a target group in public health initiatives to increase physical activity. The health-related benefits of habitual, moderate intensity physical activity are well documented in the epidemiological literature, but less is known about the effect of such physical activity on cardiorespiratory fitness. Our hypothesis was that moderate and vigorous exercise training regimens of similar estimated energy expenditure would result in similar changes in cardiorespiratory fitness. Eighteen sedentary premenopausal women with the following baseline characteristics [x +/- SE]: maximal oxygen consumption (Vo2max) = 29.5+/-1.5 ml x kg(-1) x min(-1); age = 33+/-1 years; height = 162.6+/-0.9 cm; mass = 62.7+/-2.3 kg, were randomly assigned to either vigorous (HI, 80% Vo2max, n = 10) or moderate intensity (MOD, 40% Vo2max, n = 8) cycle ergometer training groups. Exercise training was conducted 3-4 (3.37+/-0.05) days/week for 12 weeks in a supervised and progressive manner, with estimated exercise energy expenditure equated across both training groups. Vo2max and time to exhaustion increased significantly in both groups (p<0.05), with no difference between groups. Both groups had lower (p<0.05) posttraining submaximal heart rates (HR), respiratory exchange ratios (RER), and ratings of perceived exertion (RPE) during graded exercise testing, with no significant differences between the groups in posttraining values. Women participating in moderate intensity exercise training as recommended in basic public health guidelines demonstrate an increase in cardiorespiratory fitness similar to that elicited by vigorous training.

Exercise training and intensity does not alter vascular volume responses in women.

PURPOSE: The effect of endurance training on vascular volumes in females has received little research attention. Further, the effect of exercise training intensity on vascular volumes is unknown. Therefore, we investigated the hypothesis that greater hematologic changes would be induced in women by higher exercise intensity during endurance training. METHODS: There were 26 healthy, sedentary adult females with the following characteristics (mean +/- SD): maximal oxygen consumption (VO2max) = 30.0+/-6.6 ml x kg(-1) x min(-1); age = 32+/-5 yr; body mass index (BMI) = 23.7+/-3.6 kg x m(-2)) who were randomly assigned to control (CON, n = 8); high intensity (HI, 80% of VO2max, n = 10), or low intensity (LO, 40% of VO2max, n = 8) cycle ergometer training groups. Training, conducted 3-5 (3.37+/-0.05) d x wk(-1) for 12 wk, was supervised. Estimated exercise energy expenditure was equated across training groups, progressing from 150-375 kcal per session (mean +/- SE across training weeks = 298+/-0.34 and 297+/-0.37 kcal per session for HI and LO, respectively). Plasma volume (PV, T-1824 dilution); calculated total blood (TBV) and red cell volumes (RCV); calculated total hemoglobin (THb); erythropoietin concentration ([Epo]) and selected hematologic variables were measured at baseline and weeks 2, 4, 8 and 12 of training. RESULTS: The observed relative (percent) changes in PV, TBV, RCV and THb from pre-training baseline values were not statistically significant. Decreases (p < 0.05) in hematocrit (Hct), hemoglobin ([Hb]) and RBC count were observed in both training groups. Mean corpuscular Hb (MCH) and Hb concentration (MCHC) increased (p < 0.05) during training. [Epo] was decreased at week 2 compared with baseline (p < 0.03), but was similar to baseline at weeks 4, 8 and 12. CONCLUSIONS: Within the limits of this study, endurance training did not increase PV, TBV, RCV and THb in previously sedentary females regardless of the intensity of training.

Characterization of the cryptogein binding sites on plant plasma membranes.

Cryptogein is a 98-amino acid proteinaceous elicitor of tobacco defense reactions. Specific binding of cryptogein to high affinity binding sites on tobacco plasma membranes has been previously reported (K(d) = 2 nM; number of binding sites: 220 fmol/mg of protein). In this study, biochemical characterization of cryptogein binding sites reveals that they correspond to a plasma membrane glycoprotein(s) with an N-linked carbohydrate moiety, which is involved in cryptogein binding. Radiation inactivation experiments performed on tobacco plasma membrane preparations indicated that cryptogein bound specifically to a plasma membrane component with an apparent functional molecular mass of 193 kDa. Moreover, using the homobifunctional cross-linking reagent disuccinimidyl suberate and tobacco plasma membranes incubated with (125)I-cryptogein, we identified, after SDS-polyacrylamide gel electrophoresis and autoradiography, two (125)I-cryptogein linked N-glycoproteins of about 162 and 50 kDa. Similar results were obtained using Arabidopsis thaliana and Acer pseudoplatanus plasma membrane preparations, whereas cryptogein did not induce any effects on the corresponding cell suspensions. These results suggest that either cryptogein binds to nonfunctional binding sites, homologues to those present in tobacco plasma membranes, or that a protein involved in signal transduction after cryptogein recognition is absent or inactive in both A. pseudoplatanus and A. thaliana.

Involvement of plasma membrane proteins in plant defense responses. Analysis of the cryptogein signal transduction in tobacco.

Cryptogein, a 98 amino acid protein secreted by the fungus Phytophthora cryptogea, induces a hypersensitive response and systemic acquired resistance in tobacco plants (Nicotiana tabacum var Xanthi). The mode of action of cryptogein has been studied using tobacco cell suspensions. The recognition of this elicitor by a plasma membrane receptor leads to a cascade of events including protein phosphorylation, calcium influx, potassium and chloride effluxes, plasma membrane depolarization, activation of a NADPH oxidase responsible for active oxygen species (AOS) production and cytosol acidification, activation of the pentose phosphate pathway, and activation of two mitogen-activated protein kinase (MAPK) homologues. The organization of the cryptogein responses reveals that the earliest steps of the signal transduction pathway involve plasma membrane activities. Their activation generates a complex network of second messengers which triggers the specific physiological responses. This study may contribute to our understanding of plant signaling processes because elicitors and a variety of signals including hormones, Nod factors, light, gravity and stresses share some common transduction elements and pathways.

Comparison of binding properties and early biological effects of elicitins in tobacco cells

Elicitins are a family of small proteins secreted by Phytophthora species that have a high degree of homology and elicit defense reactions in tobacco (Nicotiana tabacum). They display acidic or basic characteristics, the acidic elicitins being less efficient in inducing plant necrosis. In this study we compared the binding properties of four elicitins (two basic and two acidic) and early-induced signal transduction events (Ca2+ influx, extracellular medium alkalinization, and active oxygen species production). The affinity for tobacco plasma membrane-binding sites and the number of binding sites were similar for all four elicitins. Furthermore, elicitins compete with one another for binding sites, suggesting that they interact with the same receptor. The four elicitins induced Ca2+ influx, extracellular medium alkalinization, and the production of active oxygen species in tobacco cell suspensions, but the intensity and kinetics of these effects were different from one elicitin to another. As a general observation the concentrations that induce similar levels of biological activities were lower for basic elicitins (with the exception of cinnamomin-induced Ca2+ uptake). The qualitative similarity of early events induced by elicitins indicates a common transduction scheme, whereas fine signal transduction tuning is different in each elicitin.

Twelve weeks of endurance exercise training does not affect iron status measures in women.

OBJECTIVE: This study examined the effects of 12 weeks of endurance exercise training on iron status measures in previously inactive women and compared the effects of weight-bearing endurance exercise training and non-weight-bearing endurance exercise on iron status measures. DESIGN: Randomized, experimental study. SUBJECTS: Thirty-one healthy, inactive women (aged 23 to 43 years) with apparently normal iron stores (serum ferritin concentration > or = 20 micrograms/L) were recruited from the local area by newspaper advertisements and campus mailings. Twenty-one subjects completed the study (mean +/- standard deviation for age = 32 +/- 5 years, for body mass index = 23.1 +/- 4.9, and for maximum oxygen consumption [VO2max] = 33.8 +/- 6.3 mL/kg per minute). INTERVENTION: Subjects were randomly assigned to one of three groups: an inactive control group, a walking/running group, or a cycling group. Subjects in the two exercise groups trained three to four times per week at 80% VO2max for 12 weeks. Exercise training sessions were monitored and energy expenditure increased from 150 kcal per session (week 1) to 375 kcal per session (weeks 9 to 12). Subjects in the inactive control group were instructed to maintain their normal activity patterns for the duration of the study. All subjects were instructed to maintain their normal dietary habits. MAIN OUTCOME MEASURES: Serum ferritin concentration, serum iron concentration, percentage saturation of transferrin, total iron-binding capacity, serum haptoglobin concentration, and other selected hematologic variables were measured at baseline and at weeks 2, 4, 8, and 12. STATISTICAL ANALYSES: Repeated measures analysis of variance was used to examine group x time interactions in changes in iron status measures. Statistical significance was reached at P < .05. RESULTS: Analysis of variance indicated that serum ferritin concentration did not change significantly (P = .59) during the 12 weeks in the walking/running group (mean +/- standard deviation from 41.28 +/- 14.22 to 27.41 +/- 9.74 micrograms/L) or the cycling group (from 65.81 +/- 37.62 to 41.06 +/- 26.38 micrograms/L) compared with the control group (from 47.55 +/- 15.87 to 31.56 +/- 10.57 micrograms/L). Values for serum iron, total iron-binding capacity, percentage saturation of transferrin, and haptoglobin also did not change significantly (P > .30) in the walking/running or cycling groups compared with the control group. APPLICATIONS/CONCLUSIONS: Results of this study suggest that participation in 12 weeks of moderate-intensity endurance exercise training (walking/running or cycling) is not associated with negative effects on selected measures of iron status in healthy, previously untrained women with normal iron stores (serum ferritin > or = 20 micrograms/L).

Effects of exercise mode on hematologic adaptations to endurance training in adult females.

BACKGROUND: The subjects were 26 healthy, sedentary adult females with the following characteristics: maximal oxygen consumption (VO2max) = 32.0 +/- 7.2 ml.kg-1.min-1; age = 32 +/- 5 yr; body mass index (BMI) = 23.2 +/- 3.4 kg.m-2 who were randomly assigned to control (CON; N = 8); treadmill training (TM; N = 8); or cycle ergometer training (CY; N = 10) to test the hypothesis that hematologic adaptations to endurance exercise training are specific to mode of exercise. METHODS: Training, conducted 3-5 (3.4 +/- 0.06) d.week-1 at 80% of mode specific VO2max for 12 weeks, was supervised and progressive, with estimated exercise energy expenditure equated across training groups. Plasma volume (PV, T-1824 dilution); calculated total blood (THb) and red cell volumes (RCV); calculated total hemoglobin (THb) and other hematologic variables were measured at baseline and weeks 2, 4, 8 and 12 of training. RESULTS: Across 12 weeks of training, PV was decreased (95% of baseline) in the TM group but increased (106% of baseline) in the CY group (p = 0.06). Similar trends were observed for RCV (p = 0.15) and TBV (p = 0.08). These results are in contrast to reported changes in PV, TBV and RCV in males following training. Hemodilution was observed in both training groups, reflected by decreases (p < 0.05) in hematocrit (Hct), hemoglobin (Hb) and RC count. Mean corpuscular Hb (MCH) and Hb content (MCHC) increased (p < 0.05) with training. These changes, as well as trend toward increased (p = 0.08) mean corpuscular volume (MCV), suggested the probable presence of a RC population with a lower mean age and decreased oxyhemoglobin affinity. The possibility of Type II error cannot be discounted in these trends, which suggest that PV, TBV and RCV may be affected by mode of endurance exercise in females.

Pharmacokinetics of single intravenous and oral doses of dolasetron mesylate in healthy elderly volunteers.

Dolasetron mesylate (MDL 73,147EF, Anzemet; Hoechst Marion Roussel, Laval, Canada) is a 5-HT3 receptor antagonist undergoing clinical evaluation for use as an antiemetic agent. The pharmacokinetics of dolasetron and its reduced metabolite (MDL 74,156) were studied after administration of single intravenous and oral doses of dolasetron mesylate 2.4 mg/kg in 18 healthy elderly subjects. Expressed as the dolasetron base, this dose was 1.8 mg/kg. Dolasetron was rapidly metabolized to the reduced metabolite, which appeared in plasma within 10 minutes after intravenous or oral administration. The mean half-life (t1/2) of dolasetron was 0.24 hours after intravenous administration and 0.50 hours after oral administration. The pharmacokinetic parameters of the reduced metabolite were similar after intravenous and oral administration. The apparent absolute bioavailability of the reduced metabolite was 89%, and it had an elimination t1/2 of approximately 7 hours and an apparent volume of distribution (Vd beta) of 4.69 L/kg. Dolasetron was not detected in urine. Metabolites were excreted in urine almost completely within 24 hours of administration. The primary metabolite detected in urine was the (+)-enantiomer of the reduced metabolite, which accounted for 25.35% (+/- 7.79%) and 18.88% (+/- 7.65%) of the intravenous and oral doses, respectively. Hydroxylated metabolites accounted for 5% or less of the total dose via either route. The pharmacokinetics of the reduced metabolite after single intravenous or oral doses in elderly volunteers were consistent with pharmacokinetics observed in both young healthy men and cancer patients receiving high-dose cisplatin chemotherapy. Dosage adjustments of dolasetron mesylate on the basis of age do not appear to be necessary.

Comparative Analysis of the 16S to 23S Ribosomal Intergenic Spacer Sequences of Bacillus thuringiensis Strains and Subspecies and of Closely Related Species.

Volume 61, no. 4, p. 1624, column 2, lines 38-41: The sentence should read "For example, at position 21, the G nucleotide (Fig. 1) was present in all the ISR B. thuringiensis subspecies except for B. thuringiensis subsp. tenebrionis (Te4), which contained an A." Page 1624, column 2, line 45: "Position 62" should read "position 11." Page 1624, column 2, line 47: "Position 90" should read "position 39." Page 1624, column 2, line 49: "Position 83" should read "position 32." Page 1625, column 1, line 3: "Position 83" should read "position 32." Page 1626, column 1, line 1: "Positions 62, 90, and 165, and one deletion at position 83" should read "positions 11, 39, and 114, and one deletion at position 32." [This corrects the article on p. 1623 in vol. 61.].

Comparative analysis of the 16S to 23S ribosomal intergenic spacer sequences of Bacillus thuringiensis strains and subspecies and of closely related species.

Bacillus thuringiensis spacer regions between the 16S and 23S rRNAs were amplified with conserved primers, designated 19-mer and 23-mer primers. A spacer region of 144 bp was determined for all of 6 B. thuringiensis strains, 7 B. thuringiensis subspecies, and 11 B. thuringiensis field isolates, as well as for the closely related species Bacillus cereus and Bacillus anthracis. Computer analysis and alignment of nucleotide sequences identified three mutations and one deletion in the intergenic spacer region (ISR) of B. thuringiensis subsp. kurstaki HD-1 when compared with ISR sequences from other subspecies. The same differences were identified between the ISR of B. thuringiensis strains and the ISR of B. cereus and B. anthracis. These minor differences do not seem to be sufficient to allow the design of a species-specific oligonucleotide probe.

Multiplex polymerase chain reaction for detection and differentiation of the microbial insecticide Bacillus thuringiensis.

A rapid identification of Bacillus thuringiensis strains was established by using multiplex polymerase chain reaction (PCR). Primers of high homology specific to regions within genes encoding three major classes of B. thuringiensis crystal proteins were used to generate a PCR product profile characteristic of each strain of B. thuringiensis subsp. kurstaki. Differentiation among these strains was made on the basis of the electrophoretic pattern of the PCR products. Known B. thuringiensis subsp. kurstaki strains as well as unidentified strains isolated from insect cadavers were analyzed by PCR. Small amounts of crude sample lysates were assayed in a two-step PCR containing five primers capable of distinguishing between the strains giving products of 1,500, 858, and 653 bp for the CryIA(a) CryIA(b), and CryIA(c) genes, respectively. The method can be applied to rapidly detect the strains of B. thuringiensis subsp. kurstaki in commercial formulations and in the field.