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Background and Aim: Metabolic dysfunction‐associated steatohepatitis (MASH) is a metabolic disorder with limited treatment options. The thyroid hormone receptor (THR)‐β agonist resmetirom/MGL‐3196 (MGL) increases liver fat oxidation and has been approved for treating adult MASH. However, over 60% of patients receiving MGL treatment do not achieve MASH resolution. Therefore, we investigated the potential for combination therapy of MGL with the mitochondrial uncoupler BAM15 to improve fatty liver disease outcomes in the GAN mouse model of MASH. Methods: C57BL/6J male mice were fed GAN diet for 38 weeks before stratification and randomization to treatments including MGL, BAM15, MGL + BAM15, or no drug control for 8 weeks. Treatments were admixed in diet and mice were pair‐fed to control for drug intake. Treatment effectiveness was assessed by body weight, body composition, energy expenditure, glucose tolerance, tissue lipid content, and histological analyses. Results: MGL + BAM15 treatment resulted in better efficacy versus GAN control mice than either monotherapy in the context of energy expenditure, liver fat loss, glucose control, and fatty liver disease activity score. Improvements in ALT, liver mass, and plasma cholesterol were primarily driven by MGL, while improvements in body fat were primarily driven by BAM15. No treatments altered liver fibrosis. Conclusions: MGL + BAM15 treatment had overall better efficacy to improve metabolic outcomes in mice fed GAN diet than either monotherapy alone. These data warrant further investigation into combination therapies of THR‐β agonists and mitochondrial uncouplers for the potential treatment of disorders related to fatty liver, obesity, and insulin resistance. [ABSTRACT FROM AUTHOR]

Trialkyl phosphines PMe3 and PEt3 catalyze the 1,2‐cis‐diboration of 1,3‐butadiynes to give 1,2‐diboryl enynes. The products were utilized to synthesize 1,1,2,4‐tetraaryl enynes using a Suzuki‐Miyaura protocol and can readily undergo proto‐deborylation. [ABSTRACT FROM AUTHOR]

We report a transition metal‐free, regio‐ and stereo‐selective, phosphine‐catalyzed method for the trans hydroboration of 1,3‐diynes with pinacolborane that affords (E)‐1‐boryl‐1,3‐enynes. The reaction proceeds with excellent selectivity for boron addition to the external carbon of the 1,3‐diyne framework as unambiguously established by NMR and X‐ray crystallographic studies. The reaction displays a broad substrate scope including unsymmetrical diynes to generate products in high yield (up to 95 %). Experimental and theoretical studies suggest that phosphine attack on the alkyne is a key process in the catalytic cycle. [ABSTRACT FROM AUTHOR]

We report a chemoselective, phosphine‐catalyzed semireduction of primary and secondary propiolamides. In the presence of stoichiometric pinacolborane and catalytic n‐tributylphosphine, a variety of propiolamides were successfully converted to the corresponding acrylamides in excellent yield with (E)‐stereoselectivity. The reaction condition is tolerant of various functional groups including alkene, alkyne, ketone, or ester. Deuterium labeling studies established that the hydride from activated pinacolborane is added to the α‐carbon and the proton on the amide nitrogen is abstracted by the ß‐carbon to furnish the (E)‐acrylamides. DFT calculations revealed a clear energetic driving force for the (E)‐ over the (Z)‐isomer. [ABSTRACT FROM AUTHOR]

We report the synthesis of α‐trifluoromethylacrylates from α‐trifluoroborylacrylates via a stereoretentive radical trifluoromethylation with inexpensive reagents NaSO2CF3 and TBHP at room temperature. Under these conditions, a wide substrate scope afforded the (E)‐diastereomer exclusively in moderate to good yield. The utility of the reaction products is demonstrated in the synthesis of phenyl‐4H‐pyran, a potent and selective class of IKCa channel blockers. [ABSTRACT FROM AUTHOR]

Despite extensive research, the pathophysiology and prevention of pre‐eclampsia remain elusive, diagnosis is challenging, and pre‐eclampsia remains associated with adverse maternal and perinatal outcomes. Angiogenic biomarkers, including placental growth factor (PlGF) and soluble fms‐like tyrosine kinase 1 (sFlt‐1), have been identified as valuable biomarkers for preterm pre‐eclampsia, accelerating diagnosis and reducing maternal adverse outcomes by risk stratification, with enhanced surveillance for high‐risk women. PlGF‐based testing is increasingly being implemented in clinical practice in several countries. This review provides healthcare providers with an understanding of the evidence for PlGF‐based testing and describes the practicalities and challenges to implementation. Placental growth factor in pre‐eclampsia: evidence and implementation of testing. Placental growth factor in pre‐eclampsia: evidence and implementation of testing. [ABSTRACT FROM AUTHOR]

We report the first trans phosphinoboration of internal alkynes. With an organophosphine catalyst, alkynoate esters and the phosphinoboronate Ph2P‐Bpin are efficiently converted into the corresponding trans‐α‐phosphino‐β‐boryl acrylate products in moderate to good yield with high regio‐ and Z‐selectivity. This reaction operates under mild conditions and demonstrates good atom economy, requiring only a modest excess of the phosphinoboronate. X‐ray crystallography experiments allowed structural assignment of the unprecedented and densely functionalized (Z)‐α‐phosphino‐β‐boryl acrylate products. [ABSTRACT FROM AUTHOR]

The NaOtBu‐catalyzed mixed 1,1‐diboration of terminal alkynes using the unsymmetrical diboron reagent BpinBdan (pin = pinacolato; dan = 1,8‐diaminonaphthalene) proceeds in a regio‐ and stereoselective fashion affording moderate to high yields of 1,1‐diborylalkenes bearing orthogonal boron protecting groups. It is applicable to gram‐scale synthesis without loss of yield or selectivity. The mixed 1,1‐diborylalkene products can be utilized in Suzuki–Miyaura cross‐coupling reactions which take place selectivly at the C–B site. DFT calculations suggest the NaOtBu‐catalyzed mixed 1,1‐diboration of alkynes occurs through deprotonation of the terminal alkyne, stepwise addition of BpinBdan to the terminal carbon followed by protonation with tBuOH. Experimentally observed selective formation of (Z)‐diborylalkenes is supported by our theoretical studies. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of maternal ethnicity on the risk of adverse perinatal outcome in pregnant women with chronic hypertension.Methods: Demographic and delivery data were collated of women with chronic hypertension and singleton pregnancy who delivered at one of three UK obstetric units between 2000 and 2014. Multivariable logistic regression models were used to calculate risk ratios (RR), according to ethnic group, for adverse perinatal outcome, adjusted for other maternal characteristics including age, parity, body mass index, smoking status, deprivation index and year of delivery. The impact of maternal ethnicity on birth-weight centile calculation was investigated by comparing the birth-weight centile chart customized for ethnicity (Gestation Related Optimal Weight; GROW) with a birth-weight centile calculator that does not adjust for that factor (INTERGROWTH-21st ).Results: The study cohort included 4481 pregnancies (4045 women) with chronic hypertension. Women of white ethnicity accounted for 47% (n = 2122) of the cohort and 36% (n = 1601) were of black, 8.5% (n = 379) of Asian and 8.5% (n = 379) of other ethnicity. The overall incidence of stillbirth was 1.6%, that of preterm birth < 37 weeks was 16% and that of fetal growth restriction (birth weight < 3rd centile) was 11%. Black women, compared with white women, had the highest risk for all adverse perinatal outcomes, with stillbirth occurring in 3.1% vs 0.6% of pregnancies (adjusted RR (aRR), 5.56 (95% CI, 2.79-11.09)), preterm birth < 37 weeks in 21% vs 11% (aRR, 1.70 (95% CI, 1.43-2.01)) and birth weight < 3rd centile in 15% vs 7.4% (aRR, 2.07 (95% CI, 1.71-2.51)). Asian women, compared with white women, were also at increased risk of adverse perinatal outcome, with stillbirth occurring in 1.6% vs 0.6% (aRR, 3.03 (95% CI, 1.11-8.28)), preterm birth < 37 weeks in 20% vs 11% (aRR, 1.82 (95% CI, 1.41-2.35)) and birth weight < 3rd centile in 12% vs 7.4% (aRR, 1.69 (95% CI, 1.24-2.30)). The sensitivity and specificity for prediction of infants requiring neonatal unit admission were 40% and 93%, respectively, for those with birth weight < 3rd centile according to GROW charts, compared with 16% and 96%, respectively, for those with birth weight < 3rd centile according to INTERGROWTH-21st charts.Conclusions: Black ethnicity, compared with white, is associated with the greatest risk of adverse perinatal outcome in women with chronic hypertension, even after adjusting for other maternal characteristics. Women of Asian ethnicity are also at increased risk, but to a lesser extent. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: Raised vascular function measures are associated with adverse maternal and perinatal outcomes in low-risk pregnancy. This study aimed to evaluate the association between longitudinal vascular function parameters and adverse outcome in pregnant women with chronic hypertension, and to assess whether these measures vary according to baseline parameters such as black ethnicity.Methods: This was a nested cohort study of women with chronic hypertension and a singleton pregnancy recruited to the PANDA (Pregnancy And chronic hypertension: NifeDipine vs lAbetalol as antihypertensive treatment) study at one of three UK maternity units. Women had serial pulse-wave analyses performed using the Arteriograph®, while in a sitting position, from 12 weeks' gestation onwards. Statistical analysis was performed using random-effects logistic regression models. Longitudinal vascular parameters were compared between women who developed superimposed pre-eclampsia (SPE) and those who did not, between women who delivered a small-for-gestational-age (SGA) infant (birth weight < 10th centile) and those who delivered an infant with birth weight ≥ 10th centile and between women of black ethnicity and those of non-black ethnicity.Results: The cohort included 97 women with chronic hypertension and a singleton pregnancy, of whom 90% (n = 87) were randomized to antihypertensive treatment and 57% (n = 55) were of black ethnicity, with up to six (mean, three) longitudinal vascular function assessments. SPE was diagnosed in 18% (n = 17) of women and 30% (n = 29) of infants were SGA. In women who developed subsequent SPE, compared with those who did not, mean brachial systolic blood pressure (SBP) (148 mmHg vs 139 mmHg; P = 0.002), mean diastolic blood pressure (DBP) (87 mmHg vs 82 mmHg; P = 0.01), mean central aortic pressure (139 mmHg vs 128 mmHg; P = 0.001) and mean augmentation index (AIx-75) (29% vs 22%; P = 0.01) were significantly higher across gestation. In women who delivered a SGA infant compared to those who delivered an infant with birth weight ≥ 10th centile, mean brachial SBP (146 mmHg vs 138 mmHg; P = 0.001), mean DBP (86 mmHg vs 82 mmHg; P = 0.01), mean central aortic pressure (137 mmHg vs 127 mmHg; P < 0.0001) and mean pulse-wave velocity (9.1 m/s vs 8.5 m/s; P = 0.02) were higher across gestation. No longitudinal differences were found in vascular function parameters in women of black ethnicity compared with those of non-black ethnicity.Conclusion: There were persistent differences in vascular function parameters and brachial blood pressure throughout pregnancy in women with chronic hypertension who later developed adverse maternal or perinatal outcome. Further investigation into the possible clinical use of these findings is warranted. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

A facile method for the preparation of β-boryl-α-silyl aryl acrylamides using phenyllithium, dimethylphenylsilylpinacolborane, and propargylamides is reported. A key feature of this transition metal-free reaction is the Brønsted base deprotonation of aryl secondary propargylamide to produce a Lewis base that activates the B−Si bond, which is followed by a sequential intramolecular α-silylation- trans-β-borylation. The reaction proceeds in complete regio- and stereoselectivity. A wide variety of N- and aryl-substituted propargylamides afford trans-1,2-vinylborasilanes in high yield. The vicinal borasilane products undergo a variety of subsequent chemoselective transformations. [ABSTRACT FROM AUTHOR]

A substrate-assisted diboration of alkynamides using the unsymmetrical pinacolato-1,8-diaminonaphthalenato diboron (pinBBdan) is described. The transition-metal-free reaction proceeds in a regio- and stereoselective fashion to exclusively afford trans-vinyldiboronates in good to excellent yields. Notably, Bdan and Bpin are installed on the α- and β-carbon atoms, respectively. [ABSTRACT FROM AUTHOR]

Aims To investigate the pharmacodynamics, pharmacokinetics and safety/tolerability of blocking reuptake of bile acids using the inhibitor GSK2330672 ( GSK672) in patients with type 2 diabetes ( T2D). Methods Subjects with T2D taking metformin were enrolled in two studies in which they took metformin 850 mg twice daily for 2 weeks prior to and during the randomized treatment periods. In the first crossover study (n = 15), subjects received GSK672 45 mg, escalating to 90 mg, twice daily, or placebo for 7 days. The second parallel-group study (n = 75) investigated GSK672 10-90 mg twice daily, placebo or sitagliptin for 14 days. Results In both studies, GSK672 reduced circulating bile acids and increased serum 7-α-hydroxy-4-cholesten-3-one ( C4), an intermediate in the hepatic synthesis of bile acids. Compared with placebo, in the parallel-group study 90 mg GSK672 twice daily reduced fasting plasma glucose [ FPG; −1.21 mmol/l; 95% confidence interval ( CI) −2.14, −0.28] and weighted-mean glucose area under the curve ( AUC)0-24 h (−1.33 mmol/l; 95% CI −2.30, −0.36), as well as fasting and weighted-mean insulin AUC0-24 h. GSK672 also reduced cholesterol ( LDL, non- HDL and total cholesterol) and apolipoprotein B concentrations; the maximum LDL cholesterol reduction was ∼40%. There was no change in HDL cholesterol but there was a trend towards increased fasting triglyceride levels in the GSK672 groups compared with placebo. In both studies, the most common adverse events associated with GSK672 were gastrointestinal, mostly diarrhoea (22-100%), which appeared to be independent of dose. Conclusions In subjects with T2D on metformin, GSK672 improved glucose and lipids, but there was a high incidence of gastrointestinal adverse events. [ABSTRACT FROM AUTHOR]

Objectives To assess the diagnostic accuracy of placental growth factor ( PlGF) and ultrasound parameters to predict delivery of a small-for-gestational-age ( SGA) infant in women presenting with reduced symphysis-fundus height ( SFH). Methods This was a multicenter prospective observational study recruiting 601 women with a singleton pregnancy and reduced SFH between 24 and 37 weeks' gestation across 11 sites in the UK and Canada. Plasma PlGF concentration < 5th centile, estimated fetal weight ( EFW) < 10th centile, umbilical artery Doppler pulsatility index > 95th centile and oligohydramnios (amniotic fluid index < 5 cm) were compared as predictors for a SGA infant < 3rd customized birth-weight centile and adverse perinatal outcome. Test performance statistics were calculated for all parameters in isolation and in combination. Results Of the 601 women recruited, 592 were analyzed. For predicting delivery of SGA < 3rd centile ( n = 78), EFW < 10th centile had 58% sensitivity (95% CI, 46-69%) and 93% negative predictive value ( NPV) (95% CI, 90-95%), PlGF had 37% sensitivity (95% CI, 27-49%) and 90% NPV (95% CI, 87-93%); in combination, PlGF and EFW < 10th centile had 69% sensitivity (95% CI, 55-81%) and 93% NPV (95% CI, 89-96%). The equivalent receiver-operating characteristics ( ROC) curve areas were 0.79 (95% CI, 0.74-0.84) for EFW < 10th centile, 0.70 (95% CI, 0.63-0.77) for low PlGF and 0.82 (95% CI, 0.77-0.86) in combination. Conclusions For women presenting with reduced SFH, ultrasound parameters had modest test performance for predicting delivery of SGA < 3rd centile. PlGF performed no better than EFW < 10th centile in determining delivery of a SGA infant. © 2015 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the international society of ultrasound in obstetrics and gynecology. [ABSTRACT FROM AUTHOR]

The authors discuss aspects of the controlled trail that compares elective and selective caesarean section for preterm breech infant delivery. They are critical on the unique setting and challenging environment that obstetric labour ward provides to ensure a safe outcome for both baby and mother. Also investigated is the common practice during the time of delivery of the preterm infant presenting in the breech position.

Background Opioid-induced constipation (OIC) is a common adverse effect of opioid therapy. Aim To evaluate the long-term safety and tolerability of naloxegol, an oral, peripherally acting μ-opioid receptor antagonist (PAMORA), in patients with noncancer pain and OIC. Methods A 52-week, multicenter, open-label, randomised, parallel-group phase 3 study was conducted in out-patients taking 30-1000 morphine-equivalent units per day for ≥4 weeks. Patients were randomised 2:1 to receive naloxegol 25 mg/day or usual-care (UC; investigator-chosen laxative regimen) treatment for OIC. Results The safety set comprised 804 patients (naloxegol, n = 534; UC, n = 270). Mean exposure duration was 268 days with naloxegol and 297 days with UC. Frequency of adverse events (AEs) was 81.8% with naloxegol and 72.2% with UC. Treatment-emergent AEs occurring more frequently for naloxegol vs. UC were abdominal pain (17.8% vs. 3.3%), diarrhoea (12.9% vs. 5.9%), nausea (9.4% vs. 4.1%), headache (9.0% vs. 4.8%), flatulence (6.9% vs. 1.1%) and upper abdominal pain (5.1% vs. 1.1%). Most naloxegol-emergent gastrointestinal AEs occurred early, resolving during or after naloxegol discontinuation and were mild or moderate in severity; 11 patients discontinued due to diarrhoea and nine patients owing to abdominal pain. Pain scores and mean daily opioid doses remained stable throughout the study; no attributable opioid withdrawal AEs were observed. Two patients in each group had an adjudicated major adverse cardiovascular event unrelated to study drug; no AEs were reported nor adjudicated as bowel perforations. Conclusion In patients with noncancer pain and opioid-induced constipation, naloxegol 25 mg/day up to 52 weeks was generally safe and well tolerated. [ABSTRACT FROM AUTHOR]

Background Opioids are effective for acute and chronic pain conditions, but their use is associated with often difficult-to-manage constipation and other gastrointestinal ( GI) effects due to effects on peripheral μ-opioid receptors in the gut. The mechanism of opioid-induced constipation ( OIC) differs from that of functional constipation ( FC), and OIC may not respond as well to most first-line treatments for FC. The impact of OIC on quality of life (QoL) induces some patients to decrease or stop their opioid therapy to relieve or avoid constipation. Purpose At a roundtable meeting on OIC, a working group developed a consensus definition for OIC diagnosis across disciplines and reviewed current OIC treatments and the potential of treatments in development. By consensus, OIC is defined as follows: 'A change when initiating opioid therapy from baseline bowel habits that is characterized by any of the following: reduced bowel movement frequency, development or worsening of straining to pass bowel movements, a sense of incomplete rectal evacuation, or harder stool consistency'. The working group noted the prior validation of a patient response outcome and end point for clinical trials and recommended future efforts to create treatment guidelines and QoL measures specific for OIC. Details from the working group's discussion and consensus recommendations for patient care and research are presented in this article. [ABSTRACT FROM AUTHOR]

Copper(II)-catalyzed silylation of substituted alkynylcarbonyl compounds was investigated. Through the activation of Me2PhSiBpin in water at room temperature and open atmosphere, vinylsilanes conjugated to carbonyl groups are synthesized in high yield. A surprising diastereodivergent access to olefin geometry was discovered using a silyl conjugate addition strategy: aldehydes and ketones were Z selective while esters and amides were exclusively transformed into the E products. [ABSTRACT FROM AUTHOR]

This study examined the ability of an algorithm applied to urine drug levels of hydrocodone in healthy adult volunteers to differentiate among low, medium and high doses of hydrocodone. Twenty healthy volunteers received 20, 60 and 120 mg daily doses of hydrocodone dosed to steady-state at each level while under a naltrexone blockade. Using a florescence polarization immunoassay (FPIA), two urine samples were taken at each dosing level from each participant once steady-state was reached. The concordance was calculated for raw and adjusted FPIA urine hydrocodone values within each study participant across all doses. An analysis of medians was calculated for each of the dosage groupings using Bonett-Price confidence intervals for both raw and adjusted FPIA values. Finally, the Somers' D rank order analysis was performed for both raw and adjusted FPIA methods followed by a linear comparison of parameters to further determine which lab value reporting method produced a better fit with dosage. The concordance correlation coefficient for the pairs of raw urine FPIA values was 0·339, while the concordance correlation coefficient for the pairs of normalized FPIA values using the algorithm was 0·677. While some overlap of the confidence intervals was observed using the raw FPIA values, the intervals for the adjusted FPIA levels did not overlap between any dose levels, despite the application of a Bonferroni adjustment to correct for multiple comparisons. Results of the Somers' D analyses suggest that the adjusted FPIA method is 15% more likely to be concordant with dose than the raw value method. In contrast to raw FPIA values, an algorithm that normalizes hydrocodone urine drug levels for PH, specific gravity and lean body mass discriminates well between all three of the daily doses of hydrocodone tested (20, 60 and 120 mg), even when correcting for multiple analyses. [ABSTRACT FROM AUTHOR]

The identification of genes involved in a host's response to parasite infection provides both a means for understanding the pathways involved in immune defence and a target for examining host-parasite co-evolution. Most studies rely on a candidate gene approach derived from model systems to identify gene targets of interest, and there have been a dearth of studies geared towards providing a holistic overview of immune response from natural populations. We carried out an experiment in a natural population of red grouse ( Lagopus lagopus scoticus) to manipulate levels of Trichostrongylus tenuis parasite infection. The transcriptomic response of individuals was examined from standard cDNA and suppressive subtractive hybridization (SSH) libraries produced from gut, liver and spleen, enriching for genes expressed in response to T. tenuis infection. A total of 2209 and 3716 unique transcript sequences were identified from the cDNA and SSH libraries, respectively. Forty-five of these had Gene Ontology annotation associated with immune response. Some of these genes have previously been reported from laboratory-based studies of model species as important in immune response to gastrointestinal parasite infection; however, multiple novel genes were also identified. These may reveal novel pathways involved in the host response of grouse to T. tenuis and provide a resource that can be utilized as candidate genes in other species. [ABSTRACT FROM AUTHOR]

A central issue in ecology is in understanding the relative influences of intrinsic and extrinsic effects on population regulation. Previous studies on the cyclic population dynamics of red grouse ( Lagopus lagopus scoticus) have emphasized the destabilizing effects of either nematode parasites or territorial behaviour and aggression. The potential interacting effects of these processes, mediated through density-dependent, environmentally induced alterations of host immunocompetence influencing susceptibility to parasites have not been considered. Male red grouse at high density are more aggressive, associated with increased testosterone, which potentially could lead to reduced immunocompetence at a stage when parasites are most prevalent. This could depress individual condition, breeding performance and survival and thus drive or contribute to overall reductions in population size. Here, we characterize the transcriptomic response of grouse to nematode parasite infection and investigate how this is subsequently affected by testosterone, using a microarray approach contrasting red grouse with high and low parasite load at both high and low testosterone titre. A suite of 52 transcripts showed a significant level of up-regulation to either chronic parasite load or experimental parasite infection. Of these, 51 (98%) showed a reduced level of expression under conditions of high parasite load and high testosterone. The genes up-regulated by parasites and then down-regulated at high testosterone titre were not necessarily associated with immune response, as might be intuitively expected. The results are discussed in relation to the fitness and condition of individual red grouse and factors influencing the regulation of abundance in natural populations. [ABSTRACT FROM AUTHOR]

1. Rapid movements in fungi and plants have evolved in different species to facilitate the dispersal of spores and seeds. The mechanisms of action can differ among species, but the effectiveness of these movements has rarely, if ever, been tested. Here we show through a quantitative biomechanical analysis that the stamens of Cornus canadensis L. (bunchberry) are ideal for catapulting pollen vertically at high speeds. 2. We develop a biomechanical model to describe the explosive launch of pollen from the flowers of bunchberry. The model determines the equation of motion for the stamens based only on the morphology and measurements of the parts of the stamens. To measure the motion of the stamens to compare with our model, we analysed individual frames of a video taken at 10 000 fps. 3. The thecae of adjacent stamens dehisce in bud so that the stomia face each other, retaining pollen between neighbouring anthers. As the flowers open, pollen is accelerated vertically as long as the thecae remain in contact. Pollen is released only when the anthers move horizontally and separate. 4. The observed motion of the stamens matches the results from our model through release of the pollen. The model reveals that pollen release (horizontal movement of the anthers) occurs only after the vertical speed is at its maximum. Thus, for this particular catapult mechanism, the morphology of the stamens is optimal for launching light, dry pollen straight upwards at high speed. Pollen launched vertically at high speed both enhances insect pollination by helping to making pollen stick on visiting insects, and also allows for successful wind pollination by propelling pollen into the air column. Seed set by inflorescences in pollinator-exclosure cages further supports the ability of this flower to use wind as a pollination mechanism. [ABSTRACT FROM AUTHOR]

When administered intraperitoneally to mice 2 days before immunization with a tolerogenic dose (l09) of sheep red blood cells (SRBC), cyclosporin A (CsA; 200 mg/kg) strikingly augmented 4-day delayed-type hypersensitivity (DTH) footpad reactions. These enhanced responses were similar in magnitude to those seen in animals sensitized with an immunogenic, low-dose (106) SRBC. The stimulatory effect of CsA was observed over the dose range of 5-200 mg/kg and was obtained in animals given the drug in one injection, up to 7 days before sensitization. The augmentation of DTH was characterized by footpad swelling, intense mononuclear cell infiltration and increased deposition of 125I-fibrinogen within the challenge site. In addition, increased expression of procoagulant activity by spleen cells in response to antigen was observed. Cell transfer experiments showed that the CsA- enhanced DTH could be adoptively transferred to naive recipients. Additional transfers conducted at the time of antigen challenge suggested that, under the conditions described, CsA inhibited the action of a population of suppressor cells normally effective during DTH reactions. [ABSTRACT FROM AUTHOR]