Miracle-dz/UniFAR-FTUs huggingface dataset:
Short-term vegetable intake by young children classified by 6-n-propylthoiuracil bitter-taste phenotype.

BACKGROUND Genetic variation in sensitivity to the bitterness of 6-n-propylthiouracil (PROP) is thought to play a role in the acceptance and rejection of bitter-tasting vegetables by young children. OBJECTIVES We investigated the relation between the PROP bitter-taste phenotype and acceptance and consumption of vegetables by young children. We hypothesized that nontasters of PROP would give higher hedonic ratings to bitter-tasting vegetables and would consume more bitter vegetables than would tasters of PROP. DESIGN Sixty-five preschool children were identified as tasters (n = 24) or nontasters (n = 41) of PROP. Children were allowed to select from among 5 types of vegetables (black olives, cucumbers, carrots, red pepper, and raw broccoli) to consume in a free-choice intake test and to give hedonic ratings to the vegetables. RESULTS The nontaster children consumed more vegetables than did the taster children during the free-choice test (0.91 servings compared with 0.48 servings; P < 0.05). This difference reflected the higher consumption of the more bitter-tasting vegetables (olives, cucumber, and broccoli) by the nontaster children (P < 0.05). Only 8% of the nontaster children consumed no vegetables in the free-choice test compared with 32% of taster children (P < 0.03). The nontaster children also liked raw broccoli more than did the taster children in the hedonic test (P < 0.05). CONCLUSIONS The nontaster children consumed more vegetables, particularly the vegetables that were bitter tasting, than did the taster children during a free-choice intake test. These novel findings suggest that the PROP bitter-taste phenotype contributes to the development of vegetable acceptance and consumption patterns during early childhood.
Testicular development in male lambs prenatally exposed to a high‐starch diet

Maternal nutrition during critical gestation periods impacts on offspring in later life; effects of high‐starch maternal diet on testicular development in lambs were addressed. Dairy ewes were fed diets providing either 27% (Starch, S) or 11% (Fiber, F) of starch from mating to lambing (∼147 days; S147, F147) or for the last 75 days of gestation (S75, F75). Testes of single male lambs were measured and then sampled for histological and gene expression analyses at selected ages. Testicular dimensions and weight were similar among groups, but the total area of seminiferous tubules increased with age and tended to be higher (p = 0.057) in lambs from starch‐ than fiber‐fed ewes. Sertoli and germ cells number increased with age, but was not influenced by maternal diet. Transcript abundances of androgen receptor (AR), insulin‐like growth factor 1 (IGF1), and hydroxysteroid (17‐beta) dehydrogenase 3 (HSD17B3) was similar between S147 and F147 lambs (p > 0.1). Abundance of luteinizing hormone/choriogonadotropin receptor (LHCGR) and steroidogenic acute regulatory protein (STAR) was higher in young vs older lambs, whereas insulin‐like growth factor 2 (IGF2) levels increased with age. The expression of vascular endothelial growth factor A (VEGFA), Anti‐Müllerian hormone (AMH), IGF1, follicle stimulating hormone receptor (FSHR), and insulin‐like growth factor 2 receptor (IGF2R) was not influenced by maternal diet or lamb age (p > 0.1). In conclusion, a high‐starch maternal diet did not influence gene expression, but may have affected testicular structure in infant offspring, as seen by an increase in the total area of seminiferous tubules.
Geodesic Knots in the Figure-Eight Knot Complement

We address the problem of topologically characterising simple closed geodesics in the figure-eight knot complement. We develop ways of finding these geodesics up to isotopy in the manifold, and notice that many seem to have the lowest-volume complement amongst all curves in their homotopy class. However, we find that this is not a property of geodesics that holds in general. The question arises whether under additional conditions a geodesic knot has least-volume complement over all curves in its free homotopy class. We also investigate the family of curves arising as closed orbits in the suspension flow on the figure-eight knot complement, many but not all of which are geodesic. We are led to conclude that geodesics of small tube radii may be difficult to distinguish topologically in their free homotopy class.
Effects of maternal multiple micronutrient supplementation on fetal growth: a double-blind randomized controlled trial in rural Burkina Faso.

BACKGROUND Intrauterine growth retardation is a major predictor of child health in developing countries. OBJECTIVE We tested whether providing pregnant women with the UNICEF/WHO/UNU international multiple micronutrient preparation (UNIMMAP), rather than iron and folic acid alone, improved fetal growth and its correlates. DESIGN An intention-to-treat, double-blind, randomized controlled trial including 1426 pregnancies was carried out in rural Burkina Faso. Tablet intake was directly observed. RESULTS Pregnancy outcome was known in 96.3% of the participants. After adjustment for gestational age at delivery, both birth weight (52 g; 95% CI: 4, 100; P = 0.035) and birth length (3.6 mm; 95% CI: 0.8, 6.3; P = 0.012) were significantly higher in the UNIMMAP group. UNIMMAP had a differential effect by percentiles of birth weight and length distributions: the risk of large-for-gestational-age infants was higher in the UNIMMAP group (OR: 1.58; 95% CI: 1.04, 2.38; P = 0.03), although the risk of low birth weight remained unchanged. The effect of UNIMMAP on birth size was modified by maternal body mass index at enrollment and could be more important in multiparous women and women taking sulfadoxine-pyrimethamine. Unexpectedly, the risk of perinatal death was marginally significantly increased in the UNIMMAP group (OR: 1.78; 95% CI: 0.95, 3.32; P = 0.07), and this seemed to affect mainly primiparous women (OR: 3.44; 95% CI: 1.1, 10.7; P for interaction = 0.11). CONCLUSIONS Maternal UNIMMAP modestly but significantly increased fetal growth. The resulting benefit on infant growth and survival needs to be assessed. The possible lack of benefit and potential harm in primiparous women should be further investigated. This trial was registered at clinicaltrials.gov as NCT00642408.
Active site remodeling during the catalytic cycle in metal-dependent fructose-1,6-bisphosphate aldolases

Crystal structures of two bacterial metal (Zn2+)–dependent d-fructose-1,6-bisphosphate (FBP) aldolases in complex with substrate, analogues, and triose-P reaction products were determined to 1.5–2.0 Å resolution. The ligand complexes cryotrapped in native or mutant Helicobacter pylori aldolase crystals enabled a novel mechanistic description of FBP C3–C4 bond cleavage. The reaction mechanism uses active site remodeling during the catalytic cycle, implicating relocation of the Zn2+ cofactor that is mediated by conformational changes of active site loops. Substrate binding initiates conformational changes triggered upon P1 phosphate binding, which liberates the Zn2+-chelating His-180, allowing it to act as a general base for the proton abstraction at the FBP C4 hydroxyl group. A second zinc-chelating His-83 hydrogen bonds the substrate C4 hydroxyl group and assists cleavage by stabilizing the developing negative charge during proton abstraction. Cleavage is concerted with relocation of the metal cofactor from an interior to a surface-exposed site, thereby stabilizing the nascent enediolate form. Conserved residue Glu-142 is essential for protonation of the enediolate form prior to product release. A d-tagatose 1,6-bisphosphate enzymatic complex reveals how His-180–mediated proton abstraction controls stereospecificity of the cleavage reaction. Recognition and discrimination of the reaction products, dihydroxyacetone-P and d-glyceraldehyde 3-P, occurs via charged hydrogen bonds between hydroxyl groups of the triose-Ps and conserved residues, Asp-82 and Asp-255, respectively, and are crucial aspects of the enzyme's role in gluconeogenesis. Conformational changes in mobile loops β5-α7 and β6-α8 (containing catalytic residues Glu-142 and His-180, respectively) drive active site remodeling, enabling the relocation of the metal cofactor.
Efficacy and trial effectiveness of weekly and daily iron supplementation among pregnant women in rural Bangladesh: disentangling the issues.

BACKGROUND According to our current understanding, iron absorption with weekly iron supplements is not higher than that with daily supplements (ie, there is no mucosal block). However, community-based trials have repeatedly shown that a weekly regimen is as effective as a daily one. Furthermore, when differences in absorption are found, they are commonly smaller than would be expected on the basis of differences in the amount of iron provided. The possibility of differential compliance between the regimens needs to be evaluated to explain these findings. OBJECTIVE Taking compliance into account, we compared the efficacy and trial effectiveness of weekly and daily iron supplementation during pregnancy. DESIGN In Bangladesh, 50 antenatal centers were randomly assigned to prescribe either 2 doses of 60 mg Fe once weekly or 1 dose of 60 mg Fe/d. Compliance was monitored by using a pill bottle equipped with an electronic counting device. Hemoglobin concentrations were measured at baseline and after 4, 8, and 12 wk of supplementation. RESULTS There was no differential effect per iron tablet between weekly and daily regimens. A 12-wk daily regimen (68% compliance) produced a small but significantly greater hemoglobin response than did the weekly regimen (104% compliance). The first 20 tablets consumed produced most of the effect; after 40 tablets, there was no further response. CONCLUSIONS There was no evidence of a mucosal block in the daily regimen. Over 12 wk, 50% of the amount of iron in a daily regimen was sufficient for maximum hemoglobin effect. The weekly regimen provided a large part of this amount, explaining the limited difference in effect. It appears that the current international recommendation for iron supplementation in pregnancy is higher than necessary.
Olaparib for the treatment of breast cancer

ABSTRACT Introduction: Mutations in BRCA1 and BRCA2 genes account for around 2–3% of breast cancer events and more than 10% of triple negative breast cancers. Olaparib (Lynparza®), an orally administered PARP inhibitor, demonstrated clinical benefit in a phase III trial for mutated BRCA-positive HER2 negative metastatic breast cancer. Areas covered: This review gives an overview of available preclinical and clinical data regarding olaparib, including its chemistry, mechanism of action, pharmacokinetics and pharmacodynamics, and evidence supporting antitumor efficacy and safety profile in breast cancer patients. Expert commentary: Olaparib improves progression-free survival in germline BRCA mutated HER2 negative metastatic breast cancer patients as compared to standard chemotherapy, with a manageable toxicity profile. Efficacy is of clinical relevance especially in the context of triple negative breast cancer. However, several aspects, such as sequencing or combination of these agents with other anticancer agents and identification of appropriate biomarkers, still need to be clearly defined.
(4-Cyanophenolato)(subphthalocyaninato)boron

The crystal structure of the title compound, C31H16BN7O, (CNPhO-BsubPc) is characterized by pairs of π–π stacking interactions between the concave faces of inversion-related BsubPc fragments with a centroid–centroid distance of 3.600 (1) Å. In addition, these pairs of molecules are linked into chains along [101] through further weak π–π stacking interactions with a centroid–centroid distance of 3.8587 (9) Å. There are also weak C—H⋯π(arene) interactions within the chains.
Apolipoprotein B gene polymorphisms and serum lipids: meta-analysis of the role of genetic variation in responsiveness to diet.

BACKGROUND The genetic variance determining plasma lipid and lipoprotein concentrations may modify individual responsiveness to alterations in dietary fat and cholesterol content. OBJECTIVE The aim was to examine the role of apolipoprotein (apo) B DNA polymorphisms in responsiveness of plasma lipids and lipoproteins to diet. DESIGN A controlled dietary intervention study was conducted in 44 healthy, middle-aged subjects with a 3-mo baseline, a 1-mo fat-controlled, a 1-mo high-fat, and a 1-mo habitual diet period. We also conducted a meta-analysis of all published dietary trials, including our own. RESULTS In our own dietary study, the apo B XbaI restriction-site polymorphism affected the responsiveness to diet of the plasma LDL-cholesterol concentration (P < 0.05, repeated-measures analysis of variance). Especially during the high-fat diet, homozygous absence of the XbaI restriction site (X(-)/X(-)) was associated with a greater increase in LDL cholesterol (44 +/- 5%) than was X(+)/X(+) (27 +/- 7%) or X(+)/X(-) (40 +/- 5%). The high-fat diet also induced a larger increase in plasma LDL cholesterol in subjects with the R(-)/R(-) genotype (homozygous absence of the EcoRI restriction site) (59 +/- 10%) than in those with the R(+)/R(-) (39 +/- 6%) or R(+)/R(+) (36 +/- 4%) genotype. The M(+)/M(+) genotype (homozygous presence of the MspI restriction site) was also more responsive (41 +/- 3% increase in LDL cholesterol) than the M(+)/M(-) genotype (27 +/- 10% increase). The meta-analysis supported the finding of the significant role of the EcoRI and MspI polymorphisms, but not that of the XbaI polymorphism. CONCLUSIONS The present study indicated that the apo B EcoRI and MspI polymorphisms are associated with responsiveness to diet.
Metabolic fluctuation during a muscle contraction cycle.

Gated31P-nuclear magnetic resonance followed the metabolic fluctuation in rat gastrocnemius muscle during a contraction cycle. Within 16 ms after stimulation, the phosphocreatine (PCr) level drops 11.3% from its reference state. The PCr minimum corresponds closely to the time of maximum force contraction. Pi increases stoichiometrically, while ATP remains constant. During a twitch, PCr hydrolysis produces 3.1 μmol ATP/g tissue, which is substantially higher than the reported 0.3 μmol ATP ⋅ twitch-1 ⋅ g tissue-1 derived from steady-state experiments. The results reveal that a substantial energy fluctuation accompanies a muscle twitch.
Increased hepatic glucose production response to glucagon in trained subjects.

This study was designed to characterize the impact of endurance training on the hepatic response to glucagon. We measured the effect of glucagon on hepatic glucose production (HGP) in resting trained ( n = 8) and untrained ( n = 8) healthy male subjects (maximal rate of O2 consumption: 65.9 ± 1.6 vs. 46.8 ± 0.6 ml O2 ⋅ kg-1 ⋅ min-1, respectively, P < 0.001). Endogenous insulin and glucagon were suppressed by somatostatin (somatotropin release-inhibiting hormone) infusion (450 μg/h) over 4 h. Insulin (0.15 mU ⋅ kg-1 ⋅ min-1) was infused throughout the study, and glucagon (1.5 ng ⋅ kg-1 ⋅ min-1) was infused over the last 2 h. During the latter period, plasma glucagon and insulin remained constant at 138.2 ± 3.1 vs. 145.3 ± 2.1 ng/l and at 95.5 ± 4.5 vs. 96.2 ± 1.9 pmol/l in trained and untrained subjects, respectively. Plasma glucose increased and peaked at 11.4 ± 1.1 mmol/l in trained subjects and at 8.9 ± 0.8 mmol/l in untrained subjects ( P < 0.001). During glucagon stimulation, the mean increase in HGP area under the curve was 15.8 ± 2.8 mol ⋅ kg-1 ⋅ min-1in trained subjects compared with 7.4 ± 1.6 mol ⋅ kg-1 ⋅ min-1in untrained subjects ( P < 0.01) over the first hour and declined to 6.8 ± 2.8 and 4.9 ± 1.4 mol ⋅ kg-1 ⋅ min-1during the second hour. In conclusion, these observations indicate that endurance training is associated with an increase in HGP in response to physiological levels of glucagon, thus suggesting an increase in hepatic glucagon sensitivity.
Systemic administration of amylin increases bone mass, linear growth, and adiposity in adult male mice.

Amylin is a peptide hormone cosecreted with insulin from the pancreatic β-cells that can act as an osteoblast mitogen and as an inhibitor of bone resorption. The effects on bone of its systemic administration are uncertain. The present study addresses this question in adult male mice that were given daily subcutaneous injections of amylin (10.5 μg) or vehicle ( n = 20 in each group) for 4 wk. Histomorphometric indices of bone formation increased 30-100% in the amylin-treated group, whereas resorption indices were reduced by ∼70% ( P < 0.005 for all indices). Total bone volume in the proximal tibia was 13.5 ± 1.4% in control animals and 23.0 ± 2.0% in those receiving amylin ( P = 0.0005). Cortical width, tibial growth plate width, tibial length, body weight, and fat mass were all increased in the amylin-treated group. It is concluded that systemic administration of amylin increases skeletal mass and linear bone growth. This peptide has potential as a therapy for osteoporosis if its bone effects can be dissociated from those on soft tissue mass.
Vagal involvement in dietary regulation of nutrient transport

Bates, Sarah L. , Keith A. Sharkey, and Jon B. Meddings. Vagal involvement in dietary regulation of nutrient transport. Am. J. Physiol. 274 (Gastrointest. Liver Physiol. 37): G552–G560, 1998. —In omnivores, gradual alterations in dietary nutrient composition are observed. To efficiently absorb dietary nutrients these animals alter intestinal nutrient transporter expression to match the pattern of nutrient intake. This often involves reprogramming the crypt cell to express greater numbers of the relevant transport system. The aim of this study was to determine whether vagal afferents are involved in this adaptive process. Guinea pigs were habituated to a low-carbohydrate diet and then switched to a high-carbohydrate diet. The resultant increase in glucose transporter expression was assessed by determining rates of glucose transport in jejunal brush-border membrane vesicles. Ablation of vagal afferents was accomplished by application of capsaicin to exposed cervical vagi and confirmed using Fast blue tracer studies. We found that animals in which vagal afferents were ablated with capsaicin were unable to alter rates of glucose transport in response to an increase in dietary carbohydrate. This suggests that vagal afferents are involved in this adaptive process. These findings support a role for the vagus nerve in regulating intestinal transport function, which may be important to consider in clinical disease that involves the vagus nerve.
Calcium from milk or calcium-fortified foods does not inhibit nonheme-iron absorption from a whole diet consumed over a 4-d period.

BACKGROUND Single-meal studies have indicated that calcium inhibits iron absorption in humans. However, numerous dietary factors influence iron absorption, and the effect of calcium may not be as pronounced when calcium is served as part of a whole diet. OBJECTIVE We investigated the effect of 3 sources of calcium served with the 3 main meals on nonheme-iron absorption from a 4-d diet. DESIGN (59)Fe absorption was estimated from whole-body retention measurements in 14 women aged 21-34 y, each of whom consumed four 4-d diets in a randomized crossover design. The diets differed in the source of calcium as follows: a basic diet (BD) with a low content of calcium (224 mg Ca/d), a BD with a glass of milk served at each meal (826 mg Ca/d), a BD with calcium lactate (802 mg Ca/d), and a BD with a milk mineral isolate containing calcium (801 mg Ca/d). The 2 latter calcium sources were added to selected foods of the BD (rye bread, white bread, chocolate cake, and orange juice), and these foods were consumed with the 3 meals. All diets provided 13.2 mg Fe/d. RESULTS No significant differences in nonheme-iron absorption were found between the BD and the BD supplemented with milk, calcium lactate, or the milk mineral isolate [7.4% (95% CI: 5.3%, 10.5%), 5.2% (3.5%, 7.9%), 6.7% (5.0%, 8.9%), and 5.1% (3.2%, 7.9%), respectively; P = 0.34]. CONCLUSION Consumption of a glass of milk with the 3 main meals or of an equivalent amount of calcium from fortified foods does not decrease nonheme-iron absorption from a 4-d diet.
Nitric oxide inhibits Na+absorption across cultured alveolar type II monolayers.

We examined the mechanisms by which nitric oxide (⋅ NO) decreased vectorial Na+ transport across confluent monolayers of rat alveolar type II (ATII) cells grown on permeable supports. Amiloride (10 μM) applied to the apical side of monolayers inhibited ∼90% of the equivalent ( I eq) and the short-circuit ( I sc) current, with an half-maximal inhibitory concentration (IC50) of 0.85 μM, indicating that Na+ entry into ATII cells occurred through amiloride-sensitive Na+ channels. ⋅ NO generated by spermine NONOate and papa NONOate added to both sides of the monolayers decreased I eq and increased transepithelial resistance in a concentration-dependent fashion (IC50 = 0.4 μM ⋅ NO). These changes were prevented or reversed by addition of oxyhemoglobin (50 μM). Incubation of ATII monolayers with 8-bromoguanosine 3',5'-cyclic monophosphate (400 μM) had no effect on transepithelial Na+ transport. When the basolateral membranes of ATII cells were permeabilized with amphotericin B (10 μM) in the presence of a mucosal-to-serosal Na+ gradient (145:25 mM), ⋅ NO (generated by 100 μM papa NONOate) inhibited ∼60% of the amiloride-sensitive I sc. In addition, after permeabilization of the apical membranes, ⋅ NO inhibited the I sc[a measure of Na+-K+-adenosinetriphosphatase (ATPase) activity] by ∼60%. We concluded that ⋅ NO at noncytotoxic concentrations decreased Na+ absorption across cultured ATII monolayers by inhibiting both the amiloride-sensitive Na+ channels and Na+-K+-ATPase through guanosine 3',5'-cyclic monophosphate-independent mechanisms.
Platelet-derived lysophosphatidic acid decreases endothelial permeability in vitro.

We previously reported that platelets release a soluble factor that decreases the solute permeability of cultured bovine aortic endothelial monolayers. This factor was characterized as heat stable, trypsin sensitive, and not serotonin, adenosine, ADP, or ATP [F. R. Haselton and J. S. Alexander. Am. J. Physiol. 263 ( Lung Cell Mol. Physiol. 7): L670-L678, 1992]. We now report its identity as lysophosphatidic acid (LPA). Endothelial permeability decreases rapidly, reversibly, and repeatedly when exposed to platelet supernatants. Continuous exposure produces a sustained decrease in permeability. Methanol extracts of platelet supernatants also decrease endothelial permeability. Treatment of methanol extracts of platelet supernatants with phospholipase B or alkaline phosphatase, which modify the structure of LPA, abolishes the permeability-decreasing activity. However, activity is unaffected by treatment with phospholipase A2. This pattern of enzyme inactivation is consistent with the structure of LPA. Furthermore, synthetic 1-oleoyl-LPA rapidly and significantly decreases endothelial permeability in a concentration-dependent manner. Platelet activation does not appear to be required to produce activity in supernatants from platelet isolations, since P-selectin expression is not increased and thromboxane B2 is <14 pg/6,000 platelets. Our data show that platelets release a methanol-extractable compound with an enzyme degradation profile consistent with LPA, which decreases the permeability of endothelial monolayers in vitro. In vivo, LPA derived from platelets may be an important mediator of the transport barrier formed by the vascular endothelium.