Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Fructose on Established Lipid Targets: A Systematic Review and Meta-Analysis of Controlled Feeding Trials

Background Debate over the role of fructose in mediating cardiovascular risk remains active. To update the evidence on the effect of fructose on established therapeutic lipid targets for cardiovascular disease (low-density lipoprotein cholesterol [LDL]-C, apolipoprotein B, non-high-density lipoprotein cholesterol [HDL-C]), and metabolic syndrome (triglycerides and HDL-C), we conducted a systematic review and meta-analysis of controlled feeding trials. Methods and Results MEDLINE, EMBASE, CINHAL, and the Cochrane Library were searched through July 7, 2015 for controlled feeding trials with follow-up ≥7 days, which investigated the effect of oral fructose compared to a control carbohydrate on lipids (LDL-C, apolipoprotein B, non-HDL-C, triglycerides, and HDL-C) in participants of all health backgrounds. Two independent reviewers extracted relevant data. Data were pooled using random effects models and expressed as mean difference with 95% CI. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). Eligibility criteria were met by 51 isocaloric trials (n=943), in which fructose was provided in isocaloric exchange for other carbohydrates, and 8 hypercaloric trials (n=125), in which fructose supplemented control diets with excess calories compared to the control diets alone without the excess calories. Fructose had no effect on LDL-C, non-HDL-C, apolipoprotein B, triglycerides, or HDL-C in isocaloric trials. However, in hypercaloric trials, fructose increased apolipoprotein B (n=2 trials; mean difference = 0.18 mmol/L; 95% CI: 0.05, 0.30; P=0.005) and triglycerides (n=8 trials; mean difference = 0.26 mmol/L; 95% CI: 0.11, 0.41; P<0.001). The study is limited by small sample sizes, limited follow-up, and low quality scores of the included trials. Conclusions Pooled analyses showed that fructose only had an adverse effect on established lipid targets when added to existing diets so as to provide excess calories (+21% to 35% energy). When isocalorically exchanged for other carbohydrates, fructose had no adverse effects on blood lipids. More trials that are larger, longer, and higher quality are required. Clinical Trials Registration URL: https://www.clinicaltrials. gov/. Unique Identifier: NCT01363791.
Metabolic Profiling of the Uncaria Hook Alkaloid Geissoschizine Methyl Ether in Rat and Human Liver Microsomes Using High-Performance Liquid Chromatography with Tandem Mass Spectrometry

Geissoschizine methyl ether (GM) is an indole alkaloid found in Uncaria hook, which is a galenical constituent of yokukansan, a traditional Japanese medicine. GM has been identified as the active component responsible for anti-aggressive effects. In this study, the metabolic profiling of GM in rat and human liver microsomes was investigated. Thirteen metabolites of GM were elucidated and identified using a high-performance liquid chromatography with tandem mass spectrometry method, and their molecular structures were proposed on the basis of the characteristics of their precursor ions, product ions, and chromatographic retention times. There were no differences in the metabolites between the rat and human liver microsomes. Among the 13 identified metabolites, there were two demethylation metabolites, one dehydrogenation metabolite, three methylation metabolites, three oxidation metabolites, two water-adduct metabolites, one di-demethylation metabolite, and one water-adduct metabolite followed by oxidation. The metabolic pathways of GM were proposed on the basis of this study. This study will be helpful in understanding the metabolic routes of GM and related Uncaria hook alkaloids, and provide useful information on the pharmacokinetics and pharmacodynamics. This is the first report that describes the separation and identification of GM metabolites in rat and human liver microsomes.
Uncertainty and Investment Dynamics

This paper shows that, with (partial) irreversibility, higher uncertainty reduces the impact effect of demand shocks on investment. Uncertainty increases real option values making firms more cautious when investing or disinvesting. This is confirmed both numerically for a model with a rich mix of adjustment costs, time-varying uncertainty, and aggregation over investment decisions and time, and also empirically for a panel of manufacturing firms. These cautionary effects of uncertainty are large-going from the lower quartile to the upper quartile of the uncertainty distribution typically halves the first year investment response to demand shocks. This implies the responsiveness of firms to any given policy stimulus may be much lower in periods of high uncertainty, such as after major shocks like OPEC I and 9/11. Acknowledgements The authors would like to thank in particular two anonymous referees, and also Jerome Adda,
The association between XRCC 1 Arg 399 Gln polymorphism and endometrial cancer risk : a system review and meta-analysis

Background: The results of the association between XRCC1 Arg399Gln polymorphism and endometrial cancer are inconsistent. The aim of this study is to quantitatively evaluate the relationship between XRCC1 polymorphism and endometrial cancer risk. Methods: Medline, Embase, China National Knowledge Infrastructure and Chinese Biomedicine Databases were searched to identify eligible studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for XRCC1 Arg399Gln polymorphism and endometrial cancer were calculated in a fixedeffects model and a random effects model when appropriate. Results: A total of 6 studies (1113 cases and 1226 controls) were enrolled in this meta-analysis. Overall, no significant association was found in pooled analysis. When excluding low-quality studies, significant associations were found among Caucasian population in all model: allele contrast (Arg vs. Gln), OR = 1.58, 95% CI = 1.25-2.00; homozygote (Arg/Arg vs. Gln /Gln), OR = 2.54, 95% CI = 1.56-4.14; heterozygote (Arg/Gln vs. Gln/Gln), OR = 1.46, 95% CI = 1.03-2.07; dominant model (Arg/Arg + Arg/ Gln vs. Gln/Gln), OR = 1.69, 95% CI = 1.22-2.35; recessive model (Arg/Arg vs. Arg/Gln + Gln/Gln), OR = 1.91, 95% CI = 1.24-2.96. Conclusion: The XRCC1 Arg399Gln polymorphism may be a risk factor for endometrial cancer in Caucasians.
Impact of chemokines on the properties of spinal cord‐derived neural progenitor cells in a rat spinal cord lesion model

The existence of endogenous neural progenitor cells (NPCs) in the adult spinal cord (sc) provides the potential for tailored repair therapies after spinal cord injury (SCI). This study investigates the impact of inflammatory mediators on properties of NPC cultures derived from adult rats after SCI. The Infinite Horizon impactor was used to apply 200‐kdyn thoracic sc lesions in adult rats. Control groups received laminectomies to equivalent sc regions. Thoracic sc segments were taken for neurosphere cell cultures. Cell proliferation was found to be significantly higher in lesion groups. Neurosphere‐derived cells differentiated into neurons, oligodendroglia, and astroglia. Lesion cultures exhibited significantly higher amounts of glial fibrillary acidic protein (GFAP) mRNA (P < 0.0005) and β‐III‐tubulin mRNA (P < 0.05) compared with sham animals. Neurospheres from different treatment groups exhibited the same amounts of tumor necrosis factor‐α, interleukin (IL)−1β, and IL‐6 mRNA. C‐C chemokine receptor (CCR) expression on neurospheres was examined by real‐time RT‐PCR. CCR1 was expressed most consistently in mRNA levels in neurospheres from both treatment groups. After cell differentiation, CCR1 mRNA amounts decreased. CCR1 was detectable by immunohistochemistry in neurospheres and differentiated cells of both groups. Application of CCL3 during differentiation cycles led to significantly higher GFAP mRNA amounts in sham animals compared with CCL3‐free cultures; in contrast, CCL3 had no impact on cell differentiation in the lesion group. In conclusion, impact SCI alters differentiation tendencies and proliferation rates of adult‐derived sc NPCs. Thereby, CCR1/CCL3 promotes specifically astroglial differentiation of NPCs, which provides a potential target for future neurorestorative approaches. © 2014 Wiley Periodicals, Inc.
Oceanic Forcing on Interannual Variability of Sahel Heavy and Moderate Daily Rainfall

This article analyzes SST remote forcing on the interannual variability of Sahel summer (June–September) moderate (below 75th percentile) and heavy (above 75th percentile) daily precipitation events during the period 1981–2016. Evidence is given that interannual variability of these events is markedly different. The occurrence of moderate daily rainfall events appears to be enhanced by positive SST anomalies over the tropical North Atlantic and Mediterranean, which act to increase low-level moisture advection toward the Sahel from the equatorial and north tropical Atlantic (the opposite holds for negative SSTs anomalies). In contrast, heavy and extreme daily rainfall events seem to be linked to El Niño–Southern Oscillation (ENSO) and Mediterranean variability. Under La Niña conditions and a warmer Mediterranean, vertical atmospheric instability is increased over the Sahel and low-level moisture supply from the equatorial Atlantic is enhanced over the area (the reverse is found for opposite-sign SST anomalies). Further evidence suggests that interannual variability of Sahel rainfall is mainly dominated by the extreme events. These results have implications for seasonal forecasting of Sahel moderate and heavy precipitation events based on SST predictors, as significant predictability is found from 1 to 4 months in advance.
In Vitro Fermentation of caprine milk oligosaccharides by bifidobacteria isolated from breast-fed infants

This study was conducted to investigate the catabolism and fermentation of caprine milk oligosaccharides (CMO) by selected bifidobacteria isolated from 4 breast-fed infants. Seventeen bifidobacterial isolates consisting of 3 different species (Bifidobacterium breve, Bifidobacterium longum subsp. longum and Bifidobacterium bifidum) were investigated. A CMO-enriched fraction (CMOF) (50% oligosaccharides, 10% galacto-oligosaccharides (GOS), 20% lactose, 10% glucose and 10% galactose) from caprine cheese whey was added to a growth medium as a sole source of fermentable carbohydrate. The inclusion of the CMOF was associated with increased bifidobacterial growth for all strains compared to glucose, lactose, GOS, inulin, oligofructose, 3'-sialyl-lactose and 6'-sialyl-lactose. Only one B. bifidum strain (AGR2166) was able to utilize the sialyl-CMO, 3'-sialyl-lactose and 6'-sialyl-lactose, as carbohydrate sources. The inclusion of CMOF increased the production of acetic and lactic acid (P < 0.001) after 36 h of anaerobic fermentation at 37°C, when compared to other fermentable substrates. Two B. bifidum strains (AGR2166 and AGR2168) utilised CMO, contained in the CMOF, to a greater extent than B. breve or B. longum subsp longum isolates, and this increased CMO utilization was associated with enhanced sialidase activity. CMOF stimulated bifidobacterial growth when compared to other tested fermentable carbohydrates and also increased the consumption of mono- and disaccharides, such as galactose and lactose present in the CMOF. These findings indicate that the dietary consumption of CMO may stimulate the growth and metabolism of intestinal Bifidobacteria spp. including B. bifidum typically found in the large intestine of breast-fed infants.
Detection of novel gene expression in paraffin‐embedded tissues by isotopic in situ hybridization in tissue microarrays

Correlating altered gene expression patterns with particular disease states is a critical step in understanding disease processes and developing treatment strategies. Many thousands of novel gene sequences have recently been annotated in public and private databases and are now available for analysis. Tissue‐specific expression patterns of these sequences can be evaluated physically on DNA arrays and other high throughput assays, or virtually by bioinformatics mining of expressed sequence tag (EST) databases. As a secondary screening tool, in situ hybridisation (ISH) not only confirms tissue specificity, but also reveals what is often valuable information about cell‐type expression patterns of nov16l sequences. Due to their availability and long‐term stability at room temperature, formalin‐fixed paraffin‐embedded clinical specimens provide an invaluable resource for evaluating expression patterns of novel human genes. We describe a high‐throughput approach for identifying and quantifying the expression of novel genes in paraffin‐embedded human tissues using isotopic in situ hybridisation and tissue microarrays (TMA). Copyright © 2001 John Wiley & Sons, Ltd.
Single-molecule tools elucidate H2A.Z nucleosome composition

Summary Although distinct epigenetic marks correlate with different chromatin states, how they are integrated within single nucleosomes to generate combinatorial signals remains largely unknown. We report the successful implementation of single molecule tools constituting fluorescence correlation spectroscopy (FCS), pulse interleave excitation-based Förster resonance energy transfer (PIE-FRET) and fluorescence lifetime imaging-based FRET (FLIM-FRET) to elucidate the composition of single nucleosomes containing histone variant H2A.Z (Htz1p in yeast) in vitro and in vivo. We demonstrate that yeast nucleosomes containing Htz1p are primarily composed of H4 K12ac and H3 K4me3 but not H3 K36me3 and that these patterns are conserved in mammalian cells. Quantification of epigenetic modifications in nucleosomes will provide a new dimension to epigenetics research and lead to a better understanding of how these patterns contribute to the targeting of chromatin-binding proteins and chromatin structure during gene regulation.
Nup124p Is a Nuclear Pore Factor ofSchizosaccharomyces pombe That Is Important for Nuclear Import and Activity of Retrotransposon Tf1

ABSTRACT The long terminal repeat (LTR)-containing retrotransposon Tf1 propagates within the fission yeast Schizosaccharomyces pombe as the result of several mechanisms that are typical of both retrotransposons and retroviruses. To identify host factors that contribute to the transposition process, we mutagenized cultures ofS. pombe and screened them for strains that were unable to support Tf1 transposition. One such strain contained a mutation in a gene we named nup124. The product of this gene contains 11 FXFG repeats and is a component of the nuclear pore complex. In addition to the reduced levels of Tf1 transposition, thenup124-1 allele caused a significant reduction in the nuclear localization of Tf1 Gag. Surprisingly, the mutation innup124-1 did not cause any reduction in the growth rate, the nuclear localization of specific nuclear localization signal-containing proteins, or the cytoplasmic localization of poly(A) mRNA. A two-hybrid analysis and an in vitro precipitation assay both identified an interaction between Tf1 Gag and the N terminus of Nup124p. These results provide evidence for an unusual mechanism of nuclear import that relies on a direct interaction between a nuclear pore factor and Tf1 Gag.
What's News in Business Cycles

In this paper, we perform a structural Bayesian estimation of the contribution of anticipated shocks to business cycles in the postwar United States. Our theoretical framework is a real-business-cycle model augmented with four real rigidities: investment adjustment costs, variable capacity utilization, habit formation in consumption, and habit formation in leisure. Business cycles are assumed to be driven by permanent and stationary neutral productivity shocks, permanent investment-specific shocks, and government spending shocks. Each of these driving forces is buffeted by four types of structural innovations: unanticipated innovations and innovations anticipated one, two, and three quarters in advance. We find that anticipated shocks account for more than two thirds of predicted aggregate fluctuations.
Effects of repeated treatment with MDMA on working memory and behavioural flexibility in mice

Repeated administration of 3,4‐methylenedioxymethamphetamine (MDMA) produces dopaminergic neurotoxicity in mice. However, it is still not clear whether this exposure induces deficits in cognitive processing related to specific subsets of executive functioning. We evaluated the effects of neurotoxic and non‐neurotoxic doses of MDMA (0, 3 and 30 mg/kg, twice daily for 4 days) on working memory and attentional set‐shifting in mice, and changes in extracellular levels of dopamine (DA) in the striatum. Treatment with MDMA (30 mg/kg) disrupted performance of acquired operant alternation, and this impairment was still apparent 5 days after the last drug administration. Decreased alternation was not related to anhedonia because no differences were observed between groups in the saccharin preference test under similar experimental conditions. Correct responding on delayed alternation was increased 1 day after repeated treatment with MDMA (30 mg/kg), probably because of general behavioural quiescence. Notably, the high dose regimen of MDMA impaired attentional set‐shifting related to an increase in total perseveration errors. Finally, basal extracellular levels of DA in the striatum were not modified in mice repeatedly treated with MDMA with respect to controls. However, an acute challenge with MDMA (10 mg/kg) failed to increase DA outflow in mice receiving the highest MDMA dose (30 mg/kg), corroborating a decrease in the functionality of DA transporters. Seven days after this treatment, the effects of MDMA on DA outflow were recovered. These results suggest that repeated neurotoxic doses of MDMA produce lasting impairments in recall of alternation behaviour and reduce cognitive flexibility in mice.
A Distinct Role of the Queen in Coordinated Workload and Soil Distribution in Eusocial Naked Mole-Rats

We investigated how group members achieve collective decision-making, by considering individual intrinsic behavioural rules and behavioural mechanisms for maintaining social integration. Using a simulated burrow environment, we investigated the behavioural rules of coordinated workload for soil distribution in a eusocial mammal, the naked mole-rat (Heterocephalus glaber). We tested two predictions regarding a distinct role of the queen, a socially dominant individual in the caste system: the presence of a queen would increase the workload of other caste individuals, and the cues by a queen would affect the soil distribution. In experiment 1, we placed four individuals of various castes from the same colony into an experimental burrow. Workers exhibited the highest frequency of workload compared to other castes. The presence of a queen activated the workload by other individuals. Individuals showed a consistent workload in a particular direction so as to bias the soil distribution. These results suggest that individuals have a consensus on soil distribution and that the queen plays a distinct role. In experiment 2, we placed the odour of a queen in one of four cells and observed its effect on other individuals’ workload and soil distribution. Relative to other cells, individuals frequently dug in the queen cell so the amount of soil in the queen cell decreased. These results suggest that queen odour is an important cue in coordinated workload and soil distribution in this species.
Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease

Background Plasminogen activator inhibitor type 1 (PAI‐1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI‐1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI‐1 on CHD risk. Methods and Results To evaluate the association between PAI‐1 and CHD, we applied a 3‐step strategy. First, we investigated the observational association between PAI‐1 and CHD incidence using a systematic review based on a literature search for PAI‐1 and CHD studies. Second, we explored the causal association between PAI‐1 and CHD using a Mendelian randomization approach using summary statistics from large genome‐wide association studies. Finally, we explored the causal effect of PAI‐1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta‐analysis, the highest quantile of blood PAI‐1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age‐ and sex‐adjusted model. The effect size was reduced in studies using a multivariable‐adjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI‐1 level on CHD risk (odds ratio=1.22 per unit increase of log‐transformed PAI‐1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI‐1 on elevating blood glucose and high‐density lipoprotein cholesterol. Conclusions Our study indicates a causal effect of elevated PAI‐1 level on CHD risk, which may be mediated by glucose dysfunction.
High prevalence of knee osteoarthritis, pain, and functional limitations in female soccer players twelve years after anterior cruciate ligament injury.

OBJECTIVE To determine the prevalence of radiographic knee osteoarthritis (OA) as well as knee-related symptoms and functional limitations in female soccer players 12 years after an anterior cruciate ligament (ACL) injury. METHODS Female soccer players who sustained an ACL injury 12 years earlier were examined with standardized weight-bearing knee radiography and 2 self-administered patient questionnaires, the Knee Injury and Osteoarthritis Outcome Score questionnaire and the Short Form 36-item health survey. Joint space narrowing and osteophytes were graded according to the radiographic atlas of the Osteoarthritis Research Society International. The cutoff value to define radiographic knee OA approximated a Kellgren/Lawrence grade of 2. RESULTS Of the available cohort of 103 female soccer players, 84 (82%) answered the questionnaires and 67 (65%) consented to undergo knee radiography. The mean age at assessment was 31 years (range 26-40 years) and mean body mass index was 23 kg/m2 (range 18-40 kg/m2). Fifty-five women (82%) had radiographic changes in their index knee, and 34 (51%) fulfilled the criterion for radiographic knee OA. Of the subjects answering the questionnaires, 63 (75%) reported having symptoms affecting their knee-related quality of life, and 28 (42%) were considered to have symptomatic radiographic knee OA. Slightly more than 60% of the players had undergone reconstructive surgery of the ACL. Using multivariate analyses, surgical reconstruction was found to have no significant influence on knee symptoms. CONCLUSION A very high prevalence of radiographic knee OA, pain, and functional limitations was observed in young women who sustained an ACL tear during soccer play 12 years earlier. These findings constitute a strong rationale to direct increased efforts toward prevention and better treatment of knee injury.