Short-chain fatty acids and ceca microbiota profiles in broilers and turkeys in response to diets supplemented with phytase at varying concentrations, with or without xylanase.

Two independent studies were performed, each with a 3 × 2 factorial arrangement to compare the response in broilers and turkeys to phytase and xylanase supplementation on cecal fermentation and microbial populations. For both studies, 960 Ross 308 and 960 BUT 10 (1-day-old) were allocated to 1 of 6 experimental treatments: (1) control diet, containing the standard dose (100 g/ton) of phytase (STD-Xyl); (2) the control diet with 100 g/ton of xylanase (STD + Xyl); (3) the control diet supplemented on top with 2 fold the standard dose of phytase (200 g/ton), also referred as superdosing (SD-Xyl); (4) the superdosed diet with 100 g/ton of xylanase (SD + Xyl); (5) the control diet supplemented with 5-fold the standard dose of phytase (500 g/ton), also referred as megadosing (MD-Xyl); and (6) the megadosed diet with 100 g/ton of xylanase (MD + Xyl). Each treatment had 8 replicates of 20 animals. Broiler and turkey diets, based on wheat, soybean meal, rapeseed, and barley, and water were available ad libitum. On day 28, the cecal contents from 5 birds per pen were collected. The profile of short-chain fatty acids (SCFA) and microbiome structure (by % guanidine and cytosine [G + C] method) were analyzed. Selected % G + C fractions were used for 16S rDNA sequencing for the identification of bacteria. No treatment effects were noted on SCFA concentrations in either broilers or turkeys. Broilers fed MD diets had greater proportions of unclassified Clostridiales, Mollicutes (RF9) and Faecalibacterium. Xylanase supplementation in broilers resulted in lower proportions of Lactobacillus but increased Mollicutes (RF9), unclassified Ruminococcus, unclassified Clostridiales, and Bifidobacterium. The microbiome in turkeys was unaffected by phytase supplementation, but xylanase supplementation increased the proportions of Lachnospiraceae (Incertae sedis), Lactobacillus, and Bifidobacterium. Supplementation of turkey diets with increasing doses of phytase did not affect the cecal microbiota in contrast to what was observed in broilers. In contrast, xylanase supplementation in both species led to significant changes in the microbial populations, suggesting a positive influence through the provision of oligosaccharides.

Tall oil fatty acid inclusion in the diet improves performance and increases ileal density of lactobacilli in broiler chickens.

1. Studies were conducted with tall oil fatty acids (TOFA) to determine their effect on broiler chicken performance and ileal microbiota. TOFA, a product originating from coniferous trees and recovered by fractional distillation of side-streams from pulp production, mainly comprises free long-chain fatty acids (~90%) and resin acids (~8%). Conjugated linolenic acids and pinolenic acid are characteristic fatty acid components of TOFA. 2. TOFA products at 750 mg/kg feed were tested in two 35-day broiler chicken trials, each using a wheat soya-based diet and with 12 replicate pens per treatment. In both trials, TOFA improved body weight gain at all time points (P < 0.001) and feed conversion efficiency during the first 21 days (P < 0.01). Two different dry TOFA formulations (silica carrier and palm oil coating) were tested and showed performance effects similar to liquid TOFA. 3. Ileal digesta of the broiler chickens was analysed for total eubacteria, Lactobacillus spp., Enterococcus spp., Escherichia coli and Clostridium perfringens on days 14 and 35. TOFA significantly increased total eubacteria and lactobacilli density on day 14 (P < 0.05). There was a significant positive correlation between these bacterial groups and broiler body weight on day 14 (P < 0.01). 4. A numerical reduction in C. perfringens was observed. In vitro growth inhibition studies showed that C. perfringens was strongly inhibited by 10 mg/l TOFA (P < 0.001), while common lactobacilli were resistant to >250 mg/l. The in vitro results were thus in line with in vivo observations. 5. The mechanisms behind the bacterial shifts and their role in performance improvement are unknown. Further purification of TOFA components is needed to identify the effective agents.

Population Pharmacokinetics of Methylphenidate in Healthy Adults Emphasizing Novel and Known Effects of Several Carboxylesterase 1 (CES1) Variants.

The aim of this study was to identify demographic and genetic factors that significantly affect methylphenidate (MPH) pharmacokinetics (PK), and may help explain interindividual variability and further increase the safety of MPH. d-MPH plasma concentrations, demographic covariates, and carboxylesterase 1 (CES1) genotypes were gathered from 122 healthy adults and analyzed using nonlinear mixed effects modeling. The structural model that best described the data was a two-compartment disposition model with absorption transit compartments. Novel effects of rs115629050 and CES1 diplotypes, as well as previously reported effects of rs71647871 and body weight, were included in the final model. Assessment of the independent and combined effect of CES1 covariates identified several specific risk factors that may result in severely increased d-MPH plasma exposure.

[Culturable psychrotolerant methanotrophic bacteria in landfill cover soil].

Methanotrophs closely related to psychrotolerant members of the genera Methylobacter and Methylocella were identified in cultures enriched at 10@C from landfill cover soil samples collected in the period from April to November. Mesophilic methanotrophs of the genera Methylobacter and Methylosinus were found in cultures enriched at 20 degrees C from the same cover soil samples. A thermotolerant methanotroph related to Methylocaldum gracile was identified in the culture enriched at 40 degrees C from a sample collected in May (the temperature of the cover soil was 11.5-12.5 degrees C). In addition to methanotrophs, methylobacteria of the genera Methylotenera and Methylovorus and members of the genera Verrucomicrobium, Pseudomonas, Pseudoxanthomonas, Dokdonella, Candidatus Protochlamydia, and Thiorhodospira were also identified in the enrichment cultures. A methanotroph closely related to the psychrotolerant species Methylobacter tundripaludum (98% sequence identity of 16S r-RNA genes with the type strain SV96(T)) was isolated in pure culture. The introduction of a mixture of the methanotrophic enrichments, grown at 15 degrees C, into the landfill cover soil resulted in a decrease in methane emission from the landfill surface in autumn (October, November). The inoculum used was demonstrated to contain methanotrophs closely related to Methylobacter tundripaludum SV96.

Pharmacokinetic variability of clarithromycin and differences in CYP3A4 activity in patients with cystic fibrosis.

BACKGROUND: To investigate the correlation between CYP3A4/5 activity and clarithromycin metabolism, and between CYP3A activity and CYP3A genotype. METHODS: This is an open-label, prospective pharmacokinetic study evaluating CYP3A activity using The Erythromycin Breath Test. Eight blood samples were collected within 12h after clarithromycin 500 mg was administered orally. The clarithromycin concentrations were measured by liquid chromatography-tandem mass spectrometry. AUC, Tmax and Cmax were calculated. Selected Single Nucleotide polymorphisms in CYP3A4/5 genes were assessed by PCR and single base extension. RESULTS: Twenty-one chronically infected patients were included. An 8-fold variation in the CYP3A4 activity, 10-fold variation in AUC for clarithromycin (median 881 µg/mL × min), and a 16-fold variation in Cmax for clarithromycin (median 3.4 µg/mL) were found. A linear correlation between the CYP3A4-activity and clarithromycin metabolism was demonstrated (P < 0.05). CONCLUSION: The large variation in the clarithromycin pharmacokinetics in cystic fibrosis patients may cause treatment failure. The Erythromycin Breath Test could be valuable in identifying cystic fibrosis patients in risk of treatment failure/drug toxicity.

S-nitroso albumin enhances bone formation in a rabbit calvaria model.

Nitric oxide (NO) is a mediator involved in bone regeneration. We therefore examined the effect of the novel NO donor, S-nitroso human serum albumin (S-NO-HSA) on bone formation in a rabbit calvaria augmentation model. Circular grooves (8 mm diameter, two per animal) were created by a trephine drill in the cortical bone of 40 rabbits and titanium caps were placed on the rabbit calvaria bone filled with a collagen sponge soaked with either 100 µL S-NO-HSA (5%, 20%) or human albumin (5%, 20%). After 4 weeks the titanium hemispheres were subjected to histological and histomorphometric analysis. Bone formation and the volume of the residual collagen sponge were evaluated. S-NO-HSA treatment groups had a significantly higher volume of newly formed bone underneath the titanium hemispheres compared to the albumin control groups (5%: 15.5 ± 4.0% versus 10.6 ± 2.9%; P < 0.05; 20%: 14.0 ± 4.6% versus 6.0 ± 3.8%; P < 0.01). The volume of residual collagen sponge was also significantly lower in the S-NO-HSA groups compared to the control groups (5%: 0.4 ± 0.5% versus 2.6 ± 2.4%; P < 0.05 and 20%: 1.5 ± 2.7% versus 13.0 ± 18.7%; P < 0.01). This study demonstrates for the first time that S-NO-HSA promotes bone formation by slow NO release. Additionally, S-NO-HSA increases collagen sponge degradation.

Utility and adoption of CYP2D6 and CYP2C19 genotyping and its translation into psychiatric clinical practice.

OBJECTIVE: To describe clinical utility and adoption of routinely offered CYP2D6 and CYP2C19 genotyping (CYP test) in daily clinical practice of a psychiatric centre. METHOD: We described psychiatrists translations of CYP test results in patients with genotypes indicating poor or ultrarapid metabolizer status and treated with at least one CYP-dependent drug based on a retrospective review of medical records. Complementary, we used ethnographic participant observation and qualitative interviews to identify the barriers and incentives for the use of CYP test results. RESULTS: The cohort study included 101 of 1932 cases genotyped between 2003 and 2009. In 53 of 101 cases, test results were addressed in medical records. The most frequent response was to monitor drug concentrations (23 cases), observe for adverse events (18 cases) and adjust dosage (13 cases). In 33 of 101 cases, results were mentioned in the discharge letter. The ethnographic study indicated a poor adoption of the CYP test in clinical praxis. Test results were lost in workflows and knowledge transfer between laboratory and clinician and were absent from clinical routines, treatment conferences and educational fora. CONCLUSION: The CYP test has not gained foothold in clinical practice, and its potential clinical benefits are not utilized.

Expanding the range of ZNF804A variants conferring risk of psychosis.

A trio of genome-wide association studies recently reported sequence variants at three loci to be significantly associated with schizophrenia. No sequence polymorphism had been unequivocally (P<5 × 10(-8)) associated with schizophrenia earlier. However, one variant, rs1344706[T], had come very close. This polymorphism, located in an intron of ZNF804A, was reported to associate with schizophrenia with a P-value of 1.6 × 10(-7), and with psychosis (schizophrenia plus bipolar disorder) with a P-value of 1.0 × 10(-8). In this study, using 5164 schizophrenia cases and 20,709 controls, we replicated the association with schizophrenia (odds ratio OR = 1.08, P = 0.0029) and, by adding bipolar disorder patients, we also confirmed the association with psychosis (added N = 609, OR = 1.09, P = 0.00065). Furthermore, as it has been proposed that variants such as rs1344706[T]-common and with low relative risk-may also serve to identify regions harboring less common, higher-risk susceptibility alleles, we searched ZNF804A for large copy number variants (CNVs) in 4235 psychosis patients, 1173 patients with other psychiatric disorders and 39,481 controls. We identified two CNVs including at least part of ZNF804A in psychosis patients and no ZNF804A CNVs in controls (P = 0.013 for association with psychosis). In addition, we found a ZNF804A CNV in an anxiety patient (P = 0.0016 for association with the larger set of psychiatric disorders).

The effect of activated charcoal on drug exposure in healthy volunteers: a meta-analysis.

The objective of the study was to estimate the effect of activated charcoal (AC) administered during the first 6 h after drug intake and the effect of drug properties on drug exposure. Sixty-four controlled studies were integrated in a meta-analysis. AC administered 0-5 min after administration of a drug reduced median drug exposure by 88.4% (25-75 percentile: 65.0-96.8) (P < 0.00001). The effect of AC continued to be statistically significant when administered up to 4 h after drug intake (median reduction in drug exposure 27.4% (range 21.3-31.5%, P = 0.0006). The reduction in drug exposure was correlated with the AC/drug ratio (rho = 0.69, P < 0.0001), the volume of distribution (Vd) (rho = 0.46, P = 0.0001), and time to peak concentration (rho = 0.40, P = 0.02). We found that AC is most effective when given immediately after drug ingestion but has statistically significant effects even when given as long as 4 h after drug intake. AC appears to be most effective when given in a large dose.

Role of Toll-like receptors 2, 4, and 9 in mediating neutrophil dysfunction in alcoholic hepatitis.

Neutrophil dysfunction in alcoholic hepatitis is associated with endotoxemia and an increased incidence of infection, but the mechanism is unclear. We aimed to investigate the role of Toll-like-receptors (TLR)2, 4, and 9 in mediating neutrophil dysfunction in alcoholic hepatitis. Neutrophils from healthy volunteers were incubated with alcoholic hepatitis patients' plasma (n = 12) with and without TLR2, 4, or 9 antagonists and with and without human albumin. TLR2, 4, and 9 expression, neutrophil oxidative burst, phagocytosis, and CXCR1+2 expression were measured by FACS analysis. Patients' plasma increased oxidative burst, decreased CXCR1+2 expression, and decreased phagocytosis of normal neutrophils in association with increased expression of TLR2, 4, and 9 and depletion of ATP. Inhibition of TLR2, 4, and 9 prevented the increase in oxidative burst and the decrease in CXCR1 and CXCR2 expression but did not prevent phagocytic dysfunction. Incubation with albumin completely prevented the patient plasma induced neutrophil dysfunction. Increased expression of TLR2, 4, and 9 is associated with neutrophil dysfunction, endotoxemia, and energy depletion. TLR2, 4, and 9 inhibition does not improve phagocytosis, indicating that TLR overexpression may be the result and not the cause of neutrophil activation. Albumin, an endotoxin scavenger, prevents the deleterious effect of patients' plasma on neutrophil phagocytosis, resting burst, and TLR expression.

Large ARF guanine nucleotide exchange factors in membrane trafficking.

In eukaryotic cells membrane compartments are connected through cargo-selective vesicle trafficking mediating the exchange of components between different organelles. This exchange is essential to maintain their structural integrity and specific composition. A fundamental regulatory step in vesicle formation is the activation of small ARF GTPases by exchanging their bound GDP for GTP, which is a prerequisite for ARF-mediated effector recruitment. Activation of ARFs is catalyzed by the characteristic SEC7 domain of guanine nucleotide exchange factors (ARF-GEFs), which are classified according to their additional protein domains.The only group of ARF-GEFs conserved in mammals, yeast and plants are the large ARF-GEFs. This review summarizes recent findings on the function of large ARF-GEFs, and the use of the inhibitor Brefeldin A as a potent tool in understanding membrane trafficking. Furthermore we highlight common themes and apparent differences in large ARF-GEF function between eukaryotic kingdoms.

[Long-term survival of curatively operated gastric cancer: influence of the gender and splenectomy]. / Langzeitüberleben nach kurativer Magenkarzinomoperation: Bedeutung des Geschlechts und der Splenektomie.

BACKGROUND: Despite advances in operative technique long-term survival of curatively operated gastric cancer patients still remains poor with 5-year-survival of 25 %. Gender differences have been recognized in patients with colorectal carcinoma with a higher 5-year-survival of women. The long time-survival of the individual patient is closely dependent on his immunofunction. If a splenectomy has to be carried out, the postoperative immunofunction will be affected considerably. Thus, the question arises as to how far gender and splenectomy influence the long time-survival after curative gastric cancer surgery. METHODS: In a retrospective analysis of 505 patients with gastric cancer who had been treated between the years 1992 and 2002, a curative resection, i. e. R0, could be performed in 243 patients (48.1 %) with a definite classified tumour stadium according to the UICC (1997). The sociodemographic, operative, histomorphologic and postoperative data of each patient were collected, stratified by gender and compared using log-rank-test (survival) and chi-square-test (distribution). Multivariate analysis was performed by cox regression. The level of significance was set at p < 0.05. RESULTS: The sociodemographic, histopathologic and operative data between the two genders were comparable. The morbidity between men and women was not significant. However the rate of postoperative sepsis was higher in men (p < 0.05). With regard to the long-term survival, no difference could be shown between the two groups. However, splenectomy had a significant effect on long time-survival. Women with preserved spleen had a significantly improved five-year-survival rate as compared to women undergoing splencetomy and men with preserved spleen (p < 0.05). Multivariate analysis revealed only the tumour stage as a predictor for long time-survival in men, whereas in women the extend of lymphadenectomy and sepsis also influenced long time-survival. CONCLUSION: Long time-survival of curatively operated gastric cancer patients is gender dependent in terms of splenectomy. Therefore, gender differences should be taken into account in analysing long-term data of oncological patients.

AXL and AXR1 have redundant functions in RUB conjugation and growth and development in Arabidopsis.

Cullin-RING ubiquitin-protein ligases such as the Skp1, cullin, F-box protein (SCF) have been implicated in many growth and developmental processes in plants. Normal SCF function requires that the CUL1 subunit be post-translationally modified by related to ubiquitin (RUB), a protein related to ubiquitin. This process is mediated by two enzymes: the RUB-activating and RUB-conjugating enzymes. In Arabidopsis, the RUB-activating enzyme is a heterodimer consisting of AXR1 and ECR1. Mutations in the AXR1 gene result in a pleiotropic phenotype that includes resistance to the plant hormone auxin. Here we report that the AXL (AXR1-like) gene also functions in the RUB conjugation pathway. Overexpression of AXL in the axr1-3 background complements the axr1-3 phenotype. Biochemical analysis indicates that AXL overexpression restores CUL1 modification to the wild-type level, indicating that AXR1 and AXL have the same biochemical activity. Although the axl mutant resembles wild-type plants, the majority of axr1 axl-1 double mutants are embryo or seedling lethal. Furthermore, the axl-1 mutation reveals novel RUB-dependent processes in embryo development. We conclude that AXR1 and AXL function redundantly in the RUB conjugating pathway.

Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride.

BACKGROUND: One of the controversies in preventive medicine is, whether a general reduction in sodium intake can decrease the blood pressure of a population and thereby reduce cardiovascular mortality and morbidity. In recent years the debate has been extended by studies indicating that reducing sodium intake has effects on the hormone and lipid profile. OBJECTIVES: To estimate the effects of low sodium versus high sodium intake on systolic and diastolic blood pressure (SBP and DBP), plasma or serum levels of renin, aldosterone, catecholamines, cholesterol and triglycerides. SEARCH STRATEGY: "MEDLINE" and reference lists of relevant articles were searched from 1966 through December 2001. SELECTION CRITERIA: Studies randomising persons to low sodium and high sodium diets were included if they evaluated at least one of the above outcome parameters. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data, which were analysed by means of Review Manager 4.1. MAIN RESULTS: In 57 trials of mainly Caucasians with normal blood pressure, low sodium intake reduced SBP by -1.27 mm Hg (CI: -1.76; -0.77)(p<0.0001) and DBP by -0.54 mm Hg (CI: -0.94; -0.14) (p = 0.009) as compared to high sodium intake. In 58 trials of mainly Caucasians with elevated blood pressure, low sodium intake reduced SBP by -4.18 mm Hg (CI: -5.08; - 3.27) (p < 0.0001) and DBP by -1.98 mm Hg (CI: -2.46; -1.32) (p < 0.0001) as compared to high sodium intake. The median duration of the intervention was 8 days in the normal blood pressure trials (range 4-1100) and 28 days in the elevated blood pressure trials (range 4-365). Multiple regression analyses showed no independent effect of duration on the effect size. In 8 trials of blacks with normal or elevated blood pressure, low sodium intake reduced SBP by -6.44 mm Hg (CI: -9.13; -3.74) (p < 0.0001) and DBP by -1.98 mm Hg (CI: -4.75; 0.78) (p = 0.16) as compared to high sodium intake. The magnitude of blood pressure reduction was also greater in a single trial in Japanese patients. There was also a significant increase in plasma or serum renin, 304% (p < 0.0001), aldosterone, 322%, (p < 0.0001), noradrenaline, 30% (p < 0.0001), cholesterol, 5.4% (p < 0.0001) and LDL cholesterol, 4.6% (p < 0.004), and a borderline increase in adrenaline, 12% (p = 0.04) and triglyceride, 5.9% (p = 0.03) with low sodium intake as compared with high sodium intake. REVIEWER'S CONCLUSIONS: The magnitude of the effect in Caucasians with normal blood pressure does not warrant a general recommendation to reduce sodium intake. Reduced sodium intake in Caucasians with elevated blood pressure has a useful effect to reduce blood pressure in the short-term. The results suggest that the effect of low versus high sodium intake on blood pressure was greater in Black and Asian patients than in Caucasians. However, the number of studies in black (8) and Asian patients (1) was insufficient for different recommendations. Additional long-term trials of the effect of reduced dietary sodium intake on blood pressure, metabolic variables, morbidity and mortality are required to establish whether this is a useful prophylactic or treatment strategy.

Elevated thrombin-forming capacity of tissue factor-activated cord compared with adult plasma.

Clinically observed excellent hemostasis in neonates despite low levels of clotting factors is not completely understood so far. Therefore, we investigated whether physiological low levels of the inhibitor protein C (PC) facilitate thrombin formation in tissue factor (TF)-activated plasma samples. PC was activated by endogenously generated thrombin after addition of soluble thrombomodulin (TM). The capability of activated PC (APC) to suppress thrombin formation was significantly more pronounced in adult than in cord plasma. Addition of 4 nm of TM decreased the thrombin potential (TP) in cord plasma by 10%, and in adult plasma by 52% in the presence of 5 pm TF. We demonstrate that this low anticoagulant action of PC is attributable to the low levels of tissue factor pathway inhibitor (TFPI) and antithrombin (AT) physiologically present in cord plasma. Addition of 4 nm TM decreased the TP by 58% in cord plasma adjusted to contain TFPI and AT at adult levels in the presence of 5 pm TF. Thus, the combined low anticoagulant action of the three inhibitors APC, TFPI, and AT in cord plasma allows enhanced thrombin formation associated with shorter clotting times compared with adult plasma when low amounts of TF are applied to initiate clot formation. Although our laboratory experiments do not allow definite conclusions for various clinical situations, our data might contribute to explain excellent hemostasis in neonates despite low levels of procoagulants.

Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride.

BACKGROUND: One of the controversies in preventive medicine is, whether a general reduction in sodium intake can decrease the blood pressure of a population and thereby reduce cardiovascular mortality and morbidity. In recent years the debate has been extended by studies indicating that reducing sodium intake has effects on the hormone and lipid profile. OBJECTIVES: To estimate the effects of low sodium versus high sodium intake on systolic and diastolic blood pressure (SBP and DBP), plasma or serum levels of renin, aldosterone, catecholamines, cholesterol and triglycerides. SEARCH STRATEGY: "MEDLINE" and reference lists of relevant articles were searched from 1966 through December 2001. SELECTION CRITERIA: Studies randomising persons to low sodium and high sodium diets were included if they evaluated at least one of the above outcome parameters. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data, which were analysed by means of Review Manager 4.1. MAIN RESULTS: In 57 trials of mainly Caucasians with normal blood pressure, low sodium intake reduced SBP by -1.27 mm Hg (CI: -1.76; -0.77)(p<0.0001) and DBP by -0.54 mm Hg (CI: -0.94; -0.14) (p = 0.009) as compared to high sodium intake. In 58 trials of mainly Caucasians with elevated blood pressure, low sodium intake reduced SBP by -4.18 mm Hg (CI: -5.08; - 3.27) (p < 0.0001) and DBP by -1.98 mm Hg (CI: -2.46; -1.32) (p < 0.0001) as compared to high sodium intake. The median duration of the intervention was 8 days in the normal blood pressure trials (range 4-1100) and 28 days in the elevated blood pressure trials (range 4-365). Multiple regression analyses showed no independent effect of duration on the effect size. In 8 trials of blacks with normal or elevated blood pressure, low sodium intake reduced SBP by -6.44 mm Hg (CI: -9.13; -3.74) (p < 0.0001) and DBP by -1.98 mm Hg (CI: -4.75; 0.78) (p = 0.16) as compared to high sodium intake. The magnitude of blood pressure reduction was also greater in a single trial in Japanese patients. There was also a significant increase in plasma or serum renin, 304% (p < 0.0001), aldosterone, 322%, (p < 0.0001), noradrenaline, 30% (p < 0.0001), cholesterol, 5.4% (p < 0.0001) and LDL cholesterol, 4.6% (p < 0.004), and a borderline increase in adrenaline, 12% (p = 0.04) and triglyceride, 5.9% (p = 0.03) with low sodium intake as compared with high sodium intake. REVIEWER'S CONCLUSIONS: The magnitude of the effect in Caucasians with normal blood pressure does not warrant a general recommendation to reduce sodium intake. Reduced sodium intake in Caucasians with elevated blood pressure has a useful effect to reduce blood pressure in the short-term. The results suggest that the effect of low versus high sodium intake on blood pressure was greater in Black and Asian patients than in Caucasians. However, the number of studies in black (8) and Asian patients (1) was insufficient for different recommendations. Additional long-term trials of the effect of reduced dietary sodium intake on blood pressure, metabolic variables, morbidity and mortality are required to establish whether this is a useful prophylactic or treatment strategy.

TRIPTYCHON and CAPRICE mediate lateral inhibition during trichome and root hair patterning in Arabidopsis.

Trichome patterning in Arabidopsis is a model for the generation of a spacing pattern from initially equivalent cells. We show that the TRIPTYCHON gene that functions in lateral inhibition encodes a single-repeat MYB-related transcription factor that lacks a recognizable activation domain. It has high sequence similarity to the root hair patterning gene CAPRICE. Both genes are expressed in trichomes and act together during lateral inhibition. We further show that TRIPTYCHON and CAPRICE act redundantly in the position-dependent cell fate determination in the root epidermis. Thus, the same lateral inhibition mechanism seems to be involved in both de novo patterning and position-dependent cell determination. We propose a model explaining trichome and root hair patterning by a common mechanism.

The cell morphogenesis gene ANGUSTIFOLIA encodes a CtBP/BARS-like protein and is involved in the control of the microtubule cytoskeleton.

The ANGUSTIFOLIA (AN) gene is required for leaf hair (trichome) branching and is also involved in polarized expansion underlying organ shape. Here we show that the AN gene encodes a C-terminal binding proteins/brefeldin A ADP-ribosylated substrates (CtBP/BARS) related protein. AN is expressed at low levels in all organs and the AN protein is localized in the cytoplasm. In an mutant trichomes, the organization of the actin cytoskeleton is normal but the distribution of microtubules is aberrant. A role of AN in the control of the microtubule cytoskeleton is further supported by the finding that AN genetically and physically interacts with ZWICHEL, a kinesin motor molecule involved in trichome branching. Our data suggest that CtBP/BARS-like protein function in plants is directly associated with the microtubule cytoskeleton.