Miracle-dz/UniFAR-FTUs huggingface dataset:
Colonic fermentation of indigestible carbohydrates contributes to the second-meal effect.

BACKGROUND Low postprandial blood glucose is associated with low risk of metabolic diseases. A meal's ability to diminish the glucose response to carbohydrates eaten during the following meal is known as the "second-meal effect" (SME). The reduced glycemia elicited by low-glycemic-index (LGI) foods consumed during the first meal has been suggested as the main mechanism for SME. However, LGI foods often increase colonic fermentation because of the presence of fiber and resistant starch. OBJECTIVE The objective was to study the SME of greater fermentation of high-glycemic-index (HGI) and LGI carbohydrates eaten during a previous meal. DESIGN Ten healthy volunteers ate 3 breakfast test meals consisting of sponge cakes made with rapidly digestible, nonfermentable amylopectin starch plus cellulose (HGI meal), amylopectin starch plus the fermentable disaccharide lactulose (HGI-Lac meal), or slowly digestible, partly fermentable amylose starch plus cellulose (LGI meal). Five hours later, subjects were fed the same standard lunch containing 93 g available carbohydrates. Blood was collected for measurement of glucose, insulin, and nonesterified fatty acids (NEFAs). Breath hydrogen was measured as a marker of colonic fermentation. Postlunch gastric emptying was measured by using ultrasonography. RESULTS Both the HGI-Lac and LGI meals improved glucose tolerance at lunch. In the case of the HGI-Lac meal, this effect was concomitant with low NEFA concentrations and delayed gastric emptying. CONCLUSION Fermentable carbohydrates, independent of their effect on a food's glycemic index, have the potential to regulate postprandial responses to a second meal by reducing NEFA competition for glucose disposal and, to a minor extent, by affecting intestinal motility.
Production of egg proteins, enriched with L-leucine-13C1, for the study of protein assimilation in humans using the breath test technique.

Protein assimilation and metabolism studies are hindered by the lack of an adequate oral tracer, i.e., labeled proteins. We present a new and easily reproducible methodology for producing large amounts of egg proteins labeled with L-leucine-13C1. Laying hens were fed a 0.2% leucine-deficient food supplemented with 0.2% L-leucine-13C1 (99 atom %). At plateau, eggs containing highly enriched proteins were obtained. The 13C content of egg white relative to the total C content was 1.3371 atom %, corresponding to delta = 206%. The overall tracer recovery in egg proteins was high (40.2%), making this method financially attractive as well. Accurately measurable levels of 13CO2 in breath were obtained after ingestion of a physiological load of labeled egg white proteins. Thus, egg proteins with sufficient 13C enrichment and applicable for human protein assimilation and metabolism kinetic studies were produced in an easily reproducible and highly efficient manner.
Syllogisms delivered in an angry voice lead to improved performance and engagement of a different neural system compared to neutral voice

Despite the fact that most real-world reasoning occurs in some emotional context, very little is known about the underlying behavioral and neural implications of such context. To further understand the role of emotional context in logical reasoning we scanned 15 participants with fMRI while they engaged in logical reasoning about neutral syllogisms presented through the auditory channel in a sad, angry, or neutral tone of voice. Exposure to angry voice led to improved reasoning performance compared to exposure to sad and neutral voice. A likely explanation for this effect is that exposure to expressions of anger increases selective attention toward the relevant features of target stimuli, in this case the reasoning task. Supporting this interpretation, reasoning in the context of angry voice was accompanied by activation in the superior frontal gyrus—a region known to be associated with selective attention. Our findings contribute to a greater understanding of the neural processes that underlie reasoning in an emotional context by demonstrating that two emotional contexts, despite being of the same (negative) valence, have different effects on reasoning.
Pulmonary cachexia, systemic inflammatory profile, and the interleukin 1beta -511 single nucleotide polymorphism.

BACKGROUND Cachexia is common in chronic obstructive pulmonary disease (COPD) and is thought to be linked to an enhanced systemic inflammatory response. OBJECTIVE We investigated differences in the systemic inflammatory profile and polymorphisms in related inflammatory genes in COPD patients. DESIGN A cross-sectional study was performed in 99 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stages II-IV), who were stratified by cachexia based on fat-free mass index (FFMI; in kg/m2: <16 for men and <15 for women) and compared with healthy control subjects (HCs). Body composition was determined by bioelectrical impedance analysis. Plasma concentrations and gene polymorphisms of interleukin 1beta (IL-1beta -511), IL-6 (IL-6 -174), and the tumor necrosis factor system (TNF-alpha -308 and lymphotoxin-alpha +252) were determined. Plasma C-reactive protein, leptin, and urinary pseudouridine (as a marker of cellular protein breakdown) were measured. RESULTS Fat mass, leptin, and pseudouridine were significantly different (P < 0.001) between noncachectic patients (NCPs) and cachectic patients (CPs: n = 35); the systemic inflammatory cytokine profile was not. NCPs had a body compositional shift toward a lower fat-free mass and a higher fat mass compared with HCs. CPs and NCPs had a greater systemic inflammatory response (P < 0.05) than did HCs, as reflected in C-reactive protein, soluble TNF-R75, and IL-6 concentrations. The overall distribution of the IL-1beta -511 polymorphism was significantly different between the groups (P < 0.05). CONCLUSIONS In COPD patients, who are characterized by an elevated systemic inflammatory response, cachexia is not discriminatory for the extent of increase in inflammatory status. This study, however, indicates a potential influence of genetic predisposition on the cachexia process.
hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons

Significance Neurons are highly polarized cells. RNA-binding proteins contribute to this polarization by generating diverse subcellular transcriptomes. The RNA-binding protein hnRNP R is essential for axon growth in motoneurons. This study reports the RNA interactome for hnRNP R. The main interacting RNA of hnRNP R was the noncoding RNA 7SK. Depletion of 7SK from primary motoneurons disturbed axon growth. This effect was dependent on the interaction of 7SK with hnRNP R. Both hnRNP R and 7SK localize to axons. Loss of 7SK led to a similar depletion of axonal transcripts as loss of hnRNP R. Our data suggest that 7SK, in addition to its role in transcriptional regulation, acts in concert with hnRNP R to sort specific transcripts into axons. Disturbed RNA processing and subcellular transport contribute to the pathomechanisms of motoneuron diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. RNA-binding proteins are involved in these processes, but the mechanisms by which they regulate the subcellular diversity of transcriptomes, particularly in axons, are not understood. Heterogeneous nuclear ribonucleoprotein R (hnRNP R) interacts with several proteins involved in motoneuron diseases. It is located in axons of developing motoneurons, and its depletion causes defects in axon growth. Here, we used individual nucleotide-resolution cross-linking and immunoprecipitation (iCLIP) to determine the RNA interactome of hnRNP R in motoneurons. We identified ∼3,500 RNA targets, predominantly with functions in synaptic transmission and axon guidance. Among the RNA targets identified by iCLIP, the noncoding RNA 7SK was the top interactor of hnRNP R. We detected 7SK in the nucleus and also in the cytosol of motoneurons. In axons, 7SK localized in close proximity to hnRNP R, and depletion of hnRNP R reduced axonal 7SK. Furthermore, suppression of 7SK led to defective axon growth that was accompanied by axonal transcriptome alterations similar to those caused by hnRNP R depletion. Using a series of 7SK-deletion mutants, we show that the function of 7SK in axon elongation depends on its interaction with hnRNP R but not with the PTEF-B complex involved in transcriptional regulation. These results propose a role for 7SK as an essential interactor of hnRNP R to regulate its function in axon maintenance.
Glucocorticoids reverse leptin effects on food intake and body fat in mice without increasing NPY mRNA.

Glucocorticoid stimulation of appetite and leptin expression conflicts with leptin inhibition of food intake and suggests that glucocorticoids reduce sensitivity to leptin. To determine if glucocorticoids impair feeding and metabolic responses to leptin, we measured leptin-induced changes in food intake, body weight, hormones, carcass fat, and hypothalamic neuropeptide Y (NPY) mRNA in adrenalectomized mice with and without corticosterone replacement. Leptin infusion (0.5 μg/h) significantly decreased food intake and body weight in adrenalectomized mice. Corticosterone replacement approximating normal 24-h mean levels restored food intake but did not permit weight gain equivalent to PBS-infused controls. Corticosterone levels comparable to stress-induced production completely reversed leptin-induced reductions in weight gain and body fat, despite significant attenuation by leptin of corticosterone-induced increases in plasma insulin levels. Glucocorticoid replacement increased food intake without reversing leptin inhibition of hypothalamic NPY mRNA levels. We conclude that glucocorticoid levels within the physiological range can interfere with leptin action and that glucocorticoid effects are at least partly independent of NPY.
Endothelin-1-induced mesangial cell contraction involves activation of protein kinase C-α, -δ, and -ε.

In endothelin-1 (ET-1)-stimulated mesangial cells, to identify the independent roles of calcium and protein kinase C (PKC) causing contraction, the changes in planar surface area in response to ET-1, ionomycin, or phorbol 12-myristate 13-acetate (PMA) were compared. ET-1, PMA, and ionomycin reduced planar area to 49 ± 3%, 56 ± 3%, and 78 ± 2% of basal (means ± SE, n = 40-50 cells), respectively. ET-1 or ionomycin increased cytosolic calcium from 80 ± 7 to 220 ± 30 nM or 97 ± 10 to 192 ± 10 nM, respectively. The myosin light chain kinase inhibitor, ML-7, blunted ET-1- but not PMA-stimulated contraction (82 ± 3% and 48 ± 6% of time 0, respectively). Cells pretreated with 10 μM chelerythrine for 1 h or PMA for 24 h failed to contract to either ET-1 or PMA. To identify the specific PKC isoform response to ET-1, cytosolic, membrane, and particulate fractions of mesangial cell lysates were immunoblotted with PKC isoform-specific polyclonal antibodies. ET-1 increased membrane PKC-α, -δ, and -ε to 173 ± 30%, 162 ± 26%, and 166 ± 11% of basal ( P< 0.05 vs. basal), respectively, and decreased PKC-δ and PKC-ε in the cytosol to 56 ± 11% and 37 ± 6% of basal, respectively ( P < 0.05). ET-1 increased particulate PKC-δ and PKC-ε to 172 ± 15% and 187 ± 33% of basal ( P < 0.05), respectively. PKC-α in the cytosol and particulate fractions was not altered by ET-1, but translocation to the nucleus and cell periphery was observed by confocal immunofluorescence imaging. Ionomycin did not change PKC isoform distribution. PKC-ζ was expressed but unaltered by ET-1. Therefore, mesangial cell ET-1-stimulated contraction not only involves a calcium-dependent pathway but also includes the activation of one or more PKC-α, -δ, and -ε, but not PKC-ζ.
Effects of ACE inhibition on cardiomyocyte apoptosis in dogs with heart failure.

Cardiomyocyte apoptosis or programmed cell death has been shown to occur in end-stage explanted failed human hearts and in dogs with chronic heart failure (HF). We tested the hypothesis that early long-term monotherapy with an angiotensin-converting enzyme (ACE) inhibitor attenuates cardiomyocyte apoptosis in dogs with moderate HF. Left ventricular (LV) dysfunction (ejection fraction 30-40%) was produced in dogs by multiple sequential intracoronary microembolizations. Dogs were randomized to 3 mo of therapy with enalapril (Ena, 10 mg twice daily, n = 7) or to no therapy at all (control, n = 7). After 3 mo of therapy, dogs were euthanized and the hearts removed. Presence of nuclear DNA fragmentation (nDNAf), a marker of apoptosis, was assessed in frozen LV sections using the immunohistochemical deoxynucleotidal transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) method. Sections were also stained with ventricular anti-myosin antibody to identify cells of cardiocyte origin. From each dog, 80 fields (×40) were selected at random, 40 from LV regions bordering old infarcts and 40 from LV regions remote from any infarcts, for quantifying the number of cardiomyocyte nDNAf events per 1,000 cardiomyocytes. The average number of cardiomyocyte nDNAf events per 1,000 cardiomyocytes was significantly lower in Ena-treated dogs compared with controls (0.81 ± 0.13 vs. 2.65 ± 0.81, P < 0.029). This difference was due to a significantly lower incidence of cardiomyocyte nDNAf events in LV regions bordering scarred tissue (infarcts) in Ena-treated dogs compared with controls. We conclude that early long-term Ena therapy attenuates cardiomyocyte apoptosis in dogs with moderate HF. Attenuation of cardiomyocyte apoptosis may be one mechanism by which ACE inhibitors preserve global LV function in HF.
Digestion and absorption of 2 fat emulsions with different droplet sizes in the human digestive tract.

BACKGROUND The extent of fat emulsification affects the activity of digestive lipases in vitro and may govern digestion and absorption of dietary fat. OBJECTIVE We investigated the effect of the fat globule size of 2 enteral emulsions on fat digestion and assimilation in humans. DESIGN Healthy subjects received intragastrically a coarse (10 microm) and a fine (0.7 microm) lipid emulsion of identical composition in random order. Gastric and duodenal aspirates were collected throughout digestion to measure changes in fat droplet size, gastric and pancreatic lipase activities, and fat digestion. Blood lipids were measured postprandially for fat assimilation. RESULTS Despite an increase in droplet size in the stomach (2.75-6.20 microm), the fine emulsion retained droplets of smaller size and its lipolysis was greater than that of the coarse emulsion (36.5% compared with 15.8%; P < 0.05). In the duodenum, lipolysis of the fine emulsion was on the whole higher (73.3% compared with 46.3%). The overall 0-7-h plasma and chylomicron responses given by the areas under the curve were not significantly different between the emulsions, but the triacylglycerol peak was delayed with the fine emulsion (3 h 56 min compared with 2 h 50 min). CONCLUSIONS Fat emulsions behave differently in the digestive tract depending on their initial physicochemical properties. A lower initial fat droplet size facilitates fat digestion by gastric lipase in the stomach and duodenal lipolysis. Overall fat assimilation in healthy subjects is not affected by differences in initial droplet size because of efficient fat digestion by pancreatic lipase in the small intestine. Nevertheless, these new observations could be of interest in the enteral nutrition of subjects suffering from pancreatic insufficiency.
MEK inhibition augments Raf activity, but has variable effects on mitogenesis, in vascular smooth muscle cells.

Proteins comprising the mitogen-activated protein (MAP) kinase signaling cascade are activated by a variety of growth factors, but the precise role of this series of kinase reactions, especially Raf kinase and MAP kinase kinase (MEK), in vascular smooth muscle (VSM) cell mitogenesis is not known. In this study, a specific and selective inhibitor of MEK, PD-98059, was used to examine the role of MEK in DNA synthesis and Raf-1 activity in VSM cells stimulated with serum as well as with growth factors encompassing both tyrosine kinase and G protein-coupled receptor classes. Although significant increases in DNA synthesis are seen after stimulation of VSM cells with either 10% serum, platelet-derived growth factor (PDGF)-BB, or α-thrombin, preincubation of the cells with 50 μM PD-98059 for 1 h inhibits stimulation by PDGF and thrombin, but not by serum. There is a dose-dependent inhibition of the mitogenic effect by PD-98059 in all cases; these results are not affected when PD-98059 is added at times ranging from 4 h before to 2 h after growth factor addition (times at which PD-98059 exerts its inhibitory effect). In the presence of PD-98059, stimulated MAP kinase activity is attenuated when growth factors are added between 10 min and 4 h, times which correspond to both early and sustained phases of MAP kinase activity. In addition, Raf-1 activity is markedly increased by incubation of the cells with PD-98059, despite attenuation of hyperphosphorylation of this kinase. Thus growth factors coupled to both tyrosine kinase and G protein receptors require components of the MAP kinase cascade (MEK and/or MAP kinase) for VSM cell mitogenesis, whereas serum is capable of stimulatory effects in the absence of active MEK and MAP kinase. Furthermore, there exists a functional feedback stimulatory effect of inhibited MEK on its upstream activator Raf-1 in the case of serum as well as growth factors coupled to tyrosine kinase and G protein receptors.
Effects of moderate variations in the macronutrient content of the diet on cardiovascular disease risk factors in obese patients with the metabolic syndrome.

BACKGROUND The metabolic syndrome is a cluster of abnormalities that is accompanied by a 2-fold increase in the risk of cardiovascular disease. Even if there is full agreement that lifestyle changes to induce weight loss are the first-line approach, the ideal diet for the treatment of the metabolic syndrome remains uncertain. OBJECTIVE The objective was to compare the effects of 2 diets on cardiovascular disease risk factors in obese patients with the metabolic syndrome. DESIGN The study was carried out in 100 patients randomly assigned to either a diet relatively rich in carbohydrate [65% of energy as carbohydrate, 13% as protein, and 22% as fat (17% as unsaturated fat)] or a diet that was low in carbohydrate and high in protein and in monounsaturated fat [48% of energy as carbohydrate, 19% as protein, and 33% as fat (24% as unsaturated fat)]. RESULTS All 100 patients completed the 5-mo study. At the end of the study, all the components of the metabolic syndrome (except HDL, which did not change) decreased significantly in both groups. With the high-carbohydrate diet, a significant decrease in LDL-cholesterol concentrations was also observed. Although the extent of the resolution of the metabolic syndrome was not different between groups, the low-carbohydrate diet was associated with a greater decrease in the prevalence of hypertension (P < 0.05) and of hypertriacylglycerolemia (P < 0.001). CONCLUSION Tailoring diet interventions to the specific presentation of the metabolic syndrome may be the best way of reducing the risk factors for cardiovascular disease.
The effect of partner HIV status on motivation to take antiretroviral and isoniazid preventive therapies: a conjoint analysis

ABSTRACT Antiretroviral therapy (ART) and isoniazid preventive therapy (IPT) are important to reduce morbidity and mortality among people newly diagnosed of HIV. The successful uptake of ART and IPT requires a comprehensive understanding of patients’ motivation to take such therapies. Partners also play an important role in the decision to be initiated and retained in care. We quantified patients’ motivation to take preventive therapies (ART and IPT) and compared by partner HIV status among people newly diagnosed of HIV. We enrolled and surveyed adults (≥18 years) with a recent HIV diagnosis (<6 months) from 14 public primary care clinics in Matlosana, South Africa. Participants received eight forced-choice tasks comparing two mutually exclusive sub-sets of seven possible benefits related to preventive therapies. A linear probability model was fitted to estimate the probability of prioritizing each benefit. Tests of concordance were conducted across partner HIV status (no partner, HIV- or unknown, or HIV+). A total of 424 people completed surveys. At the time of interview, 272 (64%) were on ART and 334 (79%) had a partner or spouse. Keeping themselves healthy for their family was the most important motivator to take preventive therapies (p < 0.001). Preventing HIV transmission to partners was also highly prioritized among participants with current partners independent of partner’s HIV status (p < 0.001), but it was least prioritized among those without current partners (p = 0.72). Keeping themselves healthy was less prioritized. We demonstrate that social responsibility such as supporting family and preventing HIV transmission to partners may pose greater motivation for ART and IPT initiation and adherence compared to individual health benefits. These messages should be emphasized to provide effective patient-centered care and counseling.
Blood pressure and interactions between the angiotensin polymorphism AGT M235T and sodium intake: a cross-sectional population study.

BACKGROUND Intervention studies have indicated an interaction between the blood pressure response to a low-sodium or a low-fat and high-fruit and -vegetable diet and the angiotensinogen gene (AGT) polymorphisms G-6A and M235T. OBJECTIVE We investigated whether this interaction is also present in a large free-living population. DESIGN Urinary sodium, potassium as biomarkers of intake, and blood pressure were measured in 11 384 men and women aged 45-79 y participating in the Norfolk arm of the European Prospective Investigation of Nutrition and Cancer (EPIC). The M235T polymorphism was assessed by pyrosequencing. RESULTS Highly significant associations between sodium and blood pressure were shown for all genotypes (P < 0.001), but the regression coefficient for systolic blood pressure associated with each unit of sodium for each of the MT and TT genotypes was approximately double that for the MM homozygotes (P < 0.001 for heterogeneity between genotypes). Differences were evident at high exposures to sodium but not at low exposures. There were no significant associations between blood pressure and dietary or urinary potassium. CONCLUSIONS This large cross-sectional study supports public health recommendations to reduce salt consumption in the population as a whole, and it confirms intervention trial data showing the greatest response to intervention in persons with the AA and TT genotype in the AGT G-6A and M235T polymorphisms. Genotype effects in populations at low exposure to sodium are not likely to be seen.