Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of the respiratory tract microbiota in cystic fibrosis

Purpose of review Progression of lung disease in cystic fibrosis (CF) is punctuated by Pseudomonas aeruginosa infection and recurrent pulmonary exacerbations, and is the major determinant of a patient's life expectancy. With the advent of novel deep-sequencing techniques, polymicrobial bacterial assemblages rather than single pathogens seem to be responsible for the deterioration of pulmonary function. This review summarizes recent insights into the development of the CF respiratory tract microbiome, with its determinants and its relations to clinical parameters. Recent findings Research has moved from microbiota snapshots to intensive sampling over time, in an attempt to identify biomarkers of progression of CF lung disease. The developing respiratory tract microbiota in CF is perturbed by various endogenous and exogenous factors from the first months of life on. This work has revealed that both major pathogens such as P. aeruginosa and newly discovered players such as anaerobic species seem to contribute to CF lung disease. However, their interrelations remain to be unraveled. Summary Long-term follow-up of microbiome development and alterations in relation to progression of lung disease and treatment is recommended. Moreover, integrating this information with other systems such as the metabolome, genome, mycome and virome is likely to contribute significantly to insights into host–microbiome interactions and thereby CF lung disease pathogenesis.
Dietary fat intake and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND Findings from early observational studies have suggested that the intake of dietary fat might be a contributing factor in the etiology of prostate cancer. However, the results from more recent prospective studies do not support this hypothesis, and the possible association between different food sources of fat and prostate cancer risk also remains unclear. OBJECTIVE The objectives were to assess whether intakes of dietary fat, subtypes of fat, and fat from animal products were associated with prostate cancer risk. DESIGN This was a multicenter prospective study of 142,520 men in the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary fat intake was estimated with the use of country-specific validated food questionnaires. The association between dietary fat and risk of prostate cancer was assessed by using Cox regression, stratified by recruitment center and adjusted for height, weight, smoking, education, marital status, and energy intake. RESULTS After a median follow-up time of 8.7 y, prostate cancer was diagnosed in 2727 men. There was no significant association between dietary fat (total, saturated, monounsaturated, and polyunsaturated fat and the ratio of polyunsaturated to saturated fat) and risk of prostate cancer. The hazard ratio for prostate cancer for the highest versus the lowest quintile of total fat intake was 0.96 (95% CI: 0.84, 1.09; P for trend = 0.155). There were no significant associations between prostate cancer risk and fat from red meat, dairy products, and fish. CONCLUSION The results from this large multicenter study suggest that there is no association between dietary fat and prostate cancer risk.
Bilingual children's language abilities and early reading outcomes in Head Start and kindergarten.

PURPOSE The purpose of this study was to investigate the relationship between Head Start children's receptive language development and their kindergarten reading outcomes. METHOD Eighty-eight bilingual children who were eligible to attend Head Start for 2 years participated in the study. Growth curve models were used to examine the relationship between children's language abilities during 2 years in Head Start and end-of-kindergarten reading outcomes. RESULTS The results revealed that children's English and Spanish receptive language abilities increased during Head Start, and children's early reading abilities in English were within the typical range of monolingual norms at the end of kindergarten. Children's early reading abilities in Spanish were nearly 1 SD below the test mean or lower. The results also showed that children's growth in their English and Spanish language abilities during Head Start predicted their early reading abilities in English and Spanish. IMPLICATIONS The findings imply that preschool programs are needed that target children's growth in language and not their performance measured at a particular point in time. Also, the results demonstrate the importance of early and regular evaluation of bilingual children's development in both languages in order to monitor children's growth in their two languages.
Muscle IMP accumulation during fatiguing submaximal exercise in endurance trained and untrained men.

To examine the effect of training status on muscle metabolism during exercise, seven endurance-trained [peak oxygen uptake (V˙o 2 peak) = 65.8 ± 2.4 ml ⋅ kg-1 ⋅ min-1] and six untrained (V˙o 2 peak = 46.2 ± 1.9 ml ⋅ kg-1 ⋅ min-1) men cycled to fatigue at a work rate calculated to require 70%V˙o 2 peak. Time to exhaustion was 36% longer ( P < 0.01) in trained (TR) compared with untrained (UT) men (148 ± 11 vs. 95 ± 8 min). Although intramuscular glycogen content was reduced ( P < 0.05) in both TR and UT at fatigue, IMP, a marker of a mismatch between ATP supply and demand, was only elevated ( P < 0.01) in UT muscle at fatigue and was approximately fourfold higher at this point in UT compared with TR. These data demonstrate that fatiguing submaximal exercise was associated with a similar low level of intramuscular glycogen in both TR and UT men, but a mismatch between ATP supply and demand only occurred in UT individuals.
Primary active transport of organic anions on bile canalicular membrane in humans.

Biliary excretion of several anionic compounds was examined by assessing their ATP-dependent uptake in bile canalicular membrane vesicles (CMV) prepared from six human liver samples. 2,4-Dinitrophenyl- S-glutathione (DNP-SG), leukotriene C4(LTC4), sulfobromophthalein glutathione (BSP-SG), E3040 glucuronide (E-glu), β-estradiol 17-(β-d-glucuronide) (E2-17G), grepafloxacin glucuronide (GPFXG), pravastatin, BQ-123, and methotrexate, which are known to be substrates for the rat canalicular multispecific organic anion transporter, and taurocholic acid (TCA), a substrate for the bile acid transporter, were used as substrates. ATP-dependent and saturable uptake of TCA, DNP-SG, LTC4, E-glu, E2-17G, and GPFXG was observed in all human CMV preparations examined, suggesting that these compounds are excreted in the bile via a primary active transport system in humans. Primary active transport of the other substrates was also seen in some of CMV preparations but was negligible in the others. The ATP-dependent uptake of all the compounds exhibited a large inter-CMV variation, and there was a significant correlation between the uptake of glutathione conjugates (DNP-SG, LTC4, and BSP-SG) and glucuronides (E-glu, E2-17G, and GPFXG). However, there was no significant correlation between TCA and the other organic anions, implying that the transporters for TCA and for organic anions are different also in humans. When the average value for the ATP-dependent uptake by each preparation of human CMVs was compared with that of rat CMVs, the uptake of glutathione conjugates and nonconjugated anions (pravastatin, BQ-123, and methotrexate) in humans was ∼3- to 76-fold lower than that in rats, whereas the uptake of glucuronides was similar in the two species. Thus there is a species difference in the primary active transport of organic anions across the bile canalicular membrane that is less marked for glucuronides.
Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans.

BACKGROUND Current interest in the role of functional foods in weight control has focused on plant ingredients capable of interfering with the sympathoadrenal system. OBJECTIVE We investigated whether a green tea extract, by virtue of its high content of caffeine and catechin polyphenols, could increase 24-h energy expenditure (EE) and fat oxidation in humans. DESIGN Twenty-four-hour EE, the respiratory quotient (RQ), and the urinary excretion of nitrogen and catecholamines were measured in a respiratory chamber in 10 healthy men. On 3 separate occasions, subjects were randomly assigned among 3 treatments: green tea extract (50 mg caffeine and 90 mg epigallocatechin gallate), caffeine (50 mg), and placebo, which they ingested at breakfast, lunch, and dinner. RESULTS Relative to placebo, treatment with the green tea extract resulted in a significant increase in 24-h EE (4%; P < 0.01) and a significant decrease in 24-h RQ (from 0.88 to 0.85; P < 0.001) without any change in urinary nitrogen. Twenty-four-hour urinary norepinephrine excretion was higher during treatment with the green tea extract than with the placebo (40%, P < 0.05). Treatment with caffeine in amounts equivalent to those found in the green tea extract had no effect on EE and RQ nor on urinary nitrogen or catecholamines. CONCLUSIONS Green tea has thermogenic properties and promotes fat oxidation beyond that explained by its caffeine content per se. The green tea extract may play a role in the control of body composition via sympathetic activation of thermogenesis, fat oxidation, or both.
Semi-Dense And Concentrated Fullerene-Based Composites: Microdeformation and Strain Gradient Effects

Fullerenes are carbon micro-aggregates with closed-cage structure made of pentagons or hexagons. They are obtained through condensation of carbon vapor at different values of temperature and pressure, values that determine the geometry of the resulting structure. Their importance in technology is currently increasing due to a wide class of possible applications allowed by their mechanical and chemical properties. Typically, fullerene-based composites are sol-gel structures. When they are characterized by polymeric matrices, they may combine the optical and electronic properties of semiconductors with the mechanical features of polymers [1]. Fullerene-based composites may have inorganic or/and organic nature. Among them we may select for example • FulIerene/SiO2, • Fullerene/SiOa TiO2,
Automated Language Environment Analysis: A Research Synthesis.

Purpose The Language Environment Analysis (LENA®) represents a breakthrough in automatic speech detection because it makes one's language environment, what adults and children actually hear and say, efficiently measurable. The purpose of this article was to examine (a) current dimensions of LENA research, (b) LENA's sensitivity to differences in populations and language environments, and (c) what has been achieved in closing the Word Gap. Method From electronic and human searches, 83 peer-reviewed articles using LENA were identified, and 53 met inclusionary criteria and were included in a systematic literature review. Each article reported results of 1 study. Results Originally developed to make natural language research more efficient and feasible, systematic review identified a broad landscape of relevant LENA findings focused primarily on the environments and communications of young children but also older adults and teachers. LENA's automated speech indicators (adult input, adult-child interaction, and child production) and the audio environment were shown to meet high validity standards, including accuracy, sensitivity to individual differences, and differences in populations, settings, contexts within settings, speakers, and languages. Researchers' own analyses of LENA audio recordings have extended our knowledge of microlevel processes in adult-child interaction. To date, intervention research using LENA has consisted of small pilot experiments, primarily on the effects of brief parent education plus quantitative linguistic feedback to parents. Conclusion Evidence showed that automated analysis has made a place in the repertoire of language research and practice. Implications, limitations, and future research are discussed.
Parafoveal Photoreceptor Abnormalities in Asymptomatic Patients With RP1L1 Mutations in Families With Occult Macular Dystrophy.

Purpose To report the clinical characteristics of asymptomatic cases with RP1L1 gene mutations in four families with occult macular dystrophy (OMD). Methods Four asymptomatic cases from four families were selected from a cohort of 40 subjects (16 families) with RP1L1 pathogenic variants. Clinical data of the four asymptomatic cases and three symptomatic patients in the same families were reviewed. The three asymptomatic cases did not have any visual symptoms in either eye, and one was unilaterally affected. Ophthalmologic examinations, including spectral-domain optical coherence tomography (OCT) were performed, and the morphologic characteristics of the photoreceptor layer of the asymptomatic cases were compared to those of the symptomatic patients within the same family. Results The OCT images demonstrated photoreceptor abnormalities in the parafoveal regions in all of the four asymptomatic cases (i.e., absence of the interdigitation zone and blurring of the ellipsoid zone). However, these microstructures were preserved at the foveal center. The longitudinal reflectivity profiles clearly identified this distinct pattern in the asymptomatic cases. In contrast, no distinct abnormalities were detected by other examinations including perimetry, fundus autofluorescence images, and multifocal electroretinograms (ERGs). Conclusions The sparing of the central foveal photoreceptor layer accounts for the well-preserved visual acuity in the asymptomatic patients. The sparing may represent either the initial phase of typical OMD or a subtype of macular lesion associated with OMD. It is necessary to examine asymptomatic subjects in families with OMD because some of them may progress to the typical phenotype of OMD.
Pathway Tools version 13.0: integrated software for pathway/genome informatics and systems biology

Pathway Tools is a production-quality software environment for creating a type of model-organism database called a Pathway/Genome Database (PGDB). A PGDB such as EcoCyc integrates the evolving understanding of the genes, proteins, metabolic network and regulatory network of an organism. This article provides an overview of Pathway Tools capabilities. The software performs multiple computational inferences including prediction of metabolic pathways, prediction of metabolic pathway hole fillers and prediction of operons. It enables interactive editing of PGDBs by DB curators. It supports web publishing of PGDBs, and provides a large number of query and visualization tools. The software also supports comparative analyses of PGDBs, and provides several systems biology analyses of PGDBs including reachability analysis of metabolic networks, and interactive tracing of metabolites through a metabolic network. More than 800 PGDBs have been created using Pathway Tools by scientists around the world, many of which are curated DBs for important model organisms. Those PGDBs can be exchanged using a peer-to-peer DB sharing system called the PGDB Registry.
Long-term intake of vitamins and carotenoids and odds of early age-related cortical and posterior subcapsular lens opacities.

BACKGROUND Proper nutrition appears to protect against cataracts. Few studies have related nutrition to the odds of developing cortical or posterior subcapsular (PSC) cataracts. OBJECTIVE We assessed the relation between usual nutrient intakes and age-related cortical and PSC lens opacities. DESIGN We studied 492 nondiabetic women aged 53-73 y from the Nurses' Health Study cohort who were without previously diagnosed cataracts. Usual nutrient intake was calculated as the average intake from 5 food-frequency questionnaires collected over a 13-15-y period before the eye examination. Duration of vitamin supplement use was determined from 7 questionnaires collected during this same period. We defined cortical opacities as grade > or = 0.5 and subcapsular opacities as grade > or =0.3 of the Lens Opacities Classification System III. RESULTS Some lenses had more than one opacity. No nutrient measure was related to prevalence of opacities in the full sample, but significant interactions were seen between age and vitamin C intake (P = 0.02) for odds of cortical opacities and between smoking status and folate (P = 0.02), alpha-carotene (P = 0.02), beta-carotene (P = 0.005), and total carotenoids (P = 0.02) for odds of PSC opacities. For women aged <60 y, a vitamin C intake > or = 362 mg/d was associated with a 57% lower odds ratio (0.43; 95% CI: 0.2, 0.93) of developing a cortical cataract than was an intake <140 mg/d, and use of vitamin C supplements for > or = 10 y was associated with a 60% lower odds ratio (0.40; 0.18, 0.87) than was no vitamin C supplement use. Prevalence of PSC opacities was related to total carotenoid intake in women who never smoked (P = 0.02). CONCLUSIONS Our results support a role for vitamin C in diminishing the risk of cortical cataracts in women aged <60 y and for carotenoids in diminishing the risk of PSC cataracts in women who have never smoked.
Molecular cloning, tissue distribution, and functional expression of the human Na+/H+exchanger NHE2.

In the present report, we describe the cloning of a human colonic cDNA that describes the full-length Na+/H+exchanger (NHE) 2 coding region. The human NHE2 (hNHE2) cDNA encodes for a polypeptide of 812 amino acids with a 90% overall identity to both rabbit and rat NHE2 isoforms. In comparison with SLC9A2, recently reported as the human NHE2, the hNHE2 polypeptide is 115 amino acids longer in the NH2-terminal end and shows only an 84% DNA nucleotide sequence identity. Northern blot analysis revealed that hNHE2 message has an uneven tissue distribution, with high levels in the skeletal muscle, colon, and kidney and lower levels in the testis, prostate, ovary, and small intestine. Protein expression studies with hNHE2 clone showed that a 75-kDa protein was expressed. Stable expression of transfected full-length hNHE2 cDNA in Na+/H+exchange-deficient LAP1 cells exhibited Na+-dependent pH recovery after an acid prepulse that was inhibited by 0.1 mM amiloride. These data indicate that this cDNA is the true human NHE2 cDNA and that the encoded protein is capable of catalyzing Na+/H+exchange activity.
Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli.

BACKGROUND Broccoli consumption is associated with a reduction in the risk of cancer, particularly in persons with a functional glutathione S-transferase M1 allele, as opposed rotrose whose GSTM1 gene has been deleted. Sulforaphane, the major isothiocyanate derived from 4-methylsulfinylbutyl glucosinolate, is thought to be the main agent conferring protection. OBJECTIVE We compared sulforaphane metabolism in GSTM1-null and GSTM1-positive subjects after they consumed standard broccoli and high-glucosinolate broccoli (super broccoli). DESIGN Sixteen subjects were recruited into a randomized, 3-phase crossover dietary trial of standard broccoli, super broccoli, and water. Liquid chromatography linked to tandem mass spectrometry was used to quantify sulforaphane and its thiol conjugates in plasma and urine. RESULTS GSTM1-null subjects had slightly higher, but statistically significant, areas under the curve for sulforaphane metabolite concentrations in plasma, a greater rate of urinary excretion of sulforaphane metabolites during the first 6 h after broccoli consumption, and a higher percentage of sulforaphane excretion 24 h after ingestion than did GSTM1-positive subjects. Consumption of high-glucosinolate broccoli led to a 3-fold greater increase in the areas under the curve and maximum concentrations of sulforaphane metabolites in plasma, a greater rate of urinary excretion of sulforaphane metabolites during the first 6 h after consumption, and a lower percentage of sulforaphane excretion after its ingestion than did the consumption of standard broccoli. CONCLUSIONS GSTM1 genotypes have a significant effect on the metabolism of sulforaphane derived from standard or high-glucosinolate broccoli. It is possible that the difference in metabolism may explain the greater protection that GSTM1-positive persons gain from consuming broccoli. The potential consequences of consuming glucosinolate-enriched broccoli for GSTM1-null and -positive persons are discussed.
Phenotypic variation in sensorimotor performance among eleven inbred rat strains.

As a first step toward identifying the genes that determine sensorimotor ability (motor coordination) we subjected 11 inbred strains of rats to three different tests for this trait. Rats were tested at 13 wk of age to determine how long they could remain on 1) a rotating cylinder as the velocity of rotation increased every 5 s (1-direction rotation test), 2) a rotating cylinder that reversed direction every 5 s and increased velocity every 10 s (2-direction rotation test), and 3) a platform that was tilted 2° every 5 s from 22 to 47° (tilt test). On all three tests, rats of the PVG strain demonstrated the greatest sensorimotor ability. In contrast, rats of the MNS strain were most often represented among the group of strains that demonstrated the lowest performance on all tests. Considering all three tests, there was a 3- to 13-fold range in sensorimotor performance between the highest and lowest strains. This large divergence between the highest and lowest strains provides a genetic model that can be used to identify intermediate phenotypes and quantitative trait loci that contribute to sensorimotor ability.
Regulation of α1-antitrypsin gene expression in human intestinal epithelial cell line Caco-2 by HNF-1α and HNF-4.

There is still relatively limited information about mechanisms of gene expression in enterocytes and mechanisms by which gene expression is regulated during enterocyte differentiation. Using the human intestinal epithelial cell line Caco-2, which spontaneously differentiates from a cryptlike to a villouslike enterocyte, we have previously shown that there is a marked increase in transcription of the well-characterized α1-antitrypsin (α1-AT) gene during enterocyte differentiation. In this study we examined the possibility of identifying the cis-acting elements and trans-acting DNA-binding proteins responsible for expression of the α1-AT gene in Caco-2 cells during differentiation. Footprint analysis and electrophoretic mobility shift assays showed that hepatocyte nuclear factor-1α (HNF-1α), HNF-1β, and HNF-4 from nuclear extracts of Caco-2 cells specifically bound to two regions in the proximal promoter of the α1-AT gene. Cotransfection studies showed that HNF-1α and HNF-4 had a synergistic effect on α1-AT gene expression. RNA blot analysis showed that HNF-1α and HNF-4 mRNA levels and electrophoretic mobility shift assays showed that HNF-1α binding activity increase coordinately with α1-AT mRNA levels during differentiation of Caco-2 cells. Finally, overexpression of antisense ribozymes for HNF-1α in Caco-2 cells resulted in a selective decrease in endogenous α1-AT gene expression. Together, these results provide evidence that HNF-1α and HNF-4 play a role in the mechanism by which the α1-AT gene is upregulated during enterocyte differentiation in the model Caco-2 cell system.