Miracle-dz/UniFAR-FTUs huggingface dataset:
Free Fatty Acid–Induced Reduction in Glucose-Stimulated Insulin Secretion

OBJECTIVE—An important mechanism in the pathogenesis of type 2 diabetes in obese individuals is elevation of plasma free fatty acids (FFAs), which induce insulin resistance and chronically decrease β-cell function and mass. Our objective was to investigate the role of oxidative stress in FFA-induced decrease in β-cell function. RESEARCH DESIGN AND METHODS—We used an in vivo model of 48-h intravenous oleate infusion in Wistar rats followed by hyperglycemic clamps or islet secretion studies ex vivo and in vitro models of 48-h exposure to oleate in islets and MIN6 cells. RESULTS—Forty-eight–hour infusion of oleate decreased the insulin and C-peptide responses to a hyperglycemic clamp (P < 0.01), an effect prevented by coinfusion of the antioxidants N-acetylcysteine (NAC) and taurine. Similar to the findings in vivo, 48-h infusion of oleate decreased glucose-stimulated insulin secretion ex vivo (P < 0.01) and induced oxidative stress (P < 0.001) in isolated islets, effects prevented by coinfusion of the antioxidants NAC, taurine, or tempol (4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl). Forty-eight–hour infusion of olive oil induced oxidative stress (P < 0.001) and decreased the insulin response of isolated islets similar to oleate (P < 0.01). Islets exposed to oleate or palmitate and MIN6 cells exposed to oleate showed a decreased insulin response to high glucose and increased levels of oxidative stress (both P < 0.001), effects prevented by taurine. Real-time RT-PCR showed increased mRNA levels of antioxidant genes in MIN6 cells after oleate exposure, an effect partially prevented by taurine. CONCLUSIONS—Our data are the first demonstration that oxidative stress plays a role in the decrease in β-cell secretory function induced by prolonged exposure to FFAs in vitro and in vivo.
Psychosocial impact of dental aesthetics and desire for orthodontic treatment among Chinese undergraduate students

Objective The objective of this study is to evaluate the psychosocial impact of dental aesthetics in undergraduate students in the People’s Republic of China and to investigate the association between normal orthodontic treatment needs, psychosocial impact of dental aesthetics, and desire for orthodontic treatment. Materials and methods A cross-sectional study was carried out in two universities in a city of the People’s Republic of China with 374 young adults aged between 19 years and 24 years. The students answered a Chinese version of the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) and addressed their desire for orthodontic treatment. Objective malocclusion severity was assessed with the Index of Orthodontic Treatment Need (IOTN). Statistical analysis was performed by the SPSS software (Version 15.0). Results There was no statistical sex difference in relation to the dental health component of IOTN (P=0.893) and PIDAQ scores (P=0.06), but it was found that the desire for orthodontic treatment was significantly stronger among females. The total and subscale PIDAQ scores and malocclusion severity differed significantly among the five grades of desire (P<0.01). Significant positive correlation was found among desire for orthodontic treatment, IOTN-dental health component grades, and total or subscale PIDAQ scores (P<0.01). High correlation was found between desire and PIDAQ score (r=0.93). Conclusion The desire for orthodontic treatment is higher among female young adults who have the same orthodontic treatment needs compared to males. The desire for orthodontic treatment has high positive correlation with PIDAQ scores and increases with the increase in self-perceived psychosocial impacts of malocclusion and the needs for orthodontic treatment.
Natural Product-Derived Drugs for the Treatment of Inflammatory Bowel Diseases

Natural products have been used as drugs for millennia, and the therapeutic potential of natural products has been studied for more than a century. Since the mid-1880s, approximately 60% of drugs have originated from natural products. Recently, the importance of using natural products has increased, as has interest in discovering efficient new drugs. Natural drugs are desirable for the treatment of inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease. This review discusses the discovery and development of drugs derived from natural products for the treatment of inflammatory bowel diseases.
Structure and Function of Thyroid Hormone Plasma Membrane Transporters

Thyroid hormones (TH) cross the plasma membrane with the help of transporter proteins. As charged amino acid derivatives, TH cannot simply diffuse across a lipid bilayer membrane, despite their notorious hydrophobicity. The identification of monocarboxylate transporter 8 (MCT8, SLC16A2) as a specific and very active TH transporter paved the way to the finding that mutations in the MCT8 gene cause a syndrome of psychomotor retardation in humans. The purpose of this review is to introduce the current model of transmembrane transport and highlight the diversity of TH transmembrane transporters. The interactions of TH with plasma transfer proteins, T3 receptors, and deiodinase are summarized. It is shown that proteins may bind TH owing to their hydrophobic character in hydrophobic cavities and/or by specific polar interaction with the phenolic hydroxyl, the aminopropionic acid moiety, and by weak polar interactions with the iodine atoms. These findings are compared with our understanding of how TH transporters interact with substrate. The presumed effects of mutations in MCT8 on protein folding and transport function are explained in light of the available homology model.
A randomized crossover trial on the effect of compression stockings on nausea and vomiting in early pregnancy

Introduction This study aimed to assess the impact of wearing compression stockings on women’s quality of life (QoL) associated with nausea and vomiting in early pregnancy (NVP). Methods In this randomized, open, single-center, crossover study, 74 women were assigned 1:1 to 2 weeks with compression stockings followed by 2 weeks without or vice versa. The main outcomes were NVP-associated QoL, leg-related QoL, and dizziness, as assessed by the Nausea and Vomiting in Pregnancy Quality of Life (NVPQOL) questionnaire, Chronic Venous Disease Quality of Life (CIVIQ) questionnaire, and questions on dizziness at baseline and after each 2-week period, respectively. Daily NVP was assessed using the modified Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) questionnaire. Data were analyzed using Pearson’s chi-square and independent t-tests. Results Fifty-eight women completed the study. QoL scores improved with compression treatment; changes in mean total scores were as follows: NVPQOL, −36.7 with compression vs −21.7 without (P<0.0001); and CIVIQ, −4.5 with compression vs +1.4 without (P=0.001). Mean dizziness scores were −3.2 with compression vs −0.4 without (P<0.0001). PUQE mean total score (standard deviation) was 4.9 (2.3) with compression vs 5.5 (2.2) without (P=0.042). Discussion Wearing of compression stockings in early pregnancy may improve nausea and vomiting-associated symptoms in addition to improving QoL factors.
Density Profiles and Substructure of Dark Matter Halos: Converging Results at Ultra-High Numerical Resolution

Can dissipationless N-body simulations be used to reliably determine the structural and substructure properties of dark matter halos? A large simulation of a galaxy cluster in a cold dark matter universe is used to increase the force and mass resolution of current "high-resolution simulations" by almost an order of magnitude to examine the convergence of the important physical quantities. The cluster contains ~5 million particles within the final virial radius, Rvir ≃ 2 Mpc (with H0 = 50 km s-1 Mpc-1), and is simulated using a force resolution of 1.0 kpc (≡0.05% of Rvir); the final virial mass is 4.3 × 1014 M☉, equivalent to a circular velocity of vcirc ≡ (GM/R)1/2 ≃ 1000 km s-1 at the virial radius. The central density profile has a logarithmic slope of -1.5, identical to lower resolution studies of the same halo, indicating that the profiles measured from simulations of this resolution have converged to the "physical" limit down to scales of a few kpc (~0.2% of Rvir). In addition, the abundance and properties of substructure are consistent with those derived from lower resolution runs; from small to large galaxy scales (vcirc > 100 km s-1, m > 1011 M☉), the circular velocity function and the mass function of substructures can be approximated by power laws with slopes of ~-4 and ~-2, respectively. At the current resolution, overmerging (a numerical effect that leads to structureless virialized halos in low-resolution N-body simulations) seems to be globally unimportant for substructure halos with circular velocities of vcirc > 100 km s-1 (~10% of the cluster's vcirc). We can identify subhalos orbiting in the very central region of the cluster (R ≲ 100 kpc), and we can trace most of the cluster progenitors from high redshift to the present. The object at the cluster center (the dark matter analog of a cD galaxy) is assembled between z = 3 and z = 1 from the merging of a dozen halos with vcirc ≳ 300 km s-1. Tidal stripping and halo-halo collisions decrease the mean circular velocity of the substructure halos by ≈20% over a 5 billion yr period. We use the sample of 2000 substructure halos to explore the possibility of biases using galactic tracers in clusters: the velocity dispersions of the halos globally agree with the dark matter within ≲10%, but the halos are spatially antibiased, and in the very central region of the cluster (R/Rvir < 0.3) they show positive velocity bias (bv ≡ σv3D,halos/σv3D,DM ≃ 1.2-1.3); however, this effect appears to depend on numerical resolution.
Polynuclear aromatic hydrocarbons in crops from long-term sewage sludge amended field experiments.

This study reports on the polynuclear aromatic hydrocarbon (PAH) content of crop plants grown at three different field experiments where controlled additions of sewage sludge were made a number of years ago. Archived samples of several crops have been analysed from sludge-amended and unsludged control plots for 15 PAH compounds. Root crops and above ground plant parts were available for several years following the last applications of sludge. Although the soil PAH burden increased substantially due to sewage sludge additions, and residues of these compounds have persisted in the soils for many years, increased PAH concentrations relative to the unsludged controls were not consistently detected in plant tissues. Plant samples were relatively enriched with low molecular weight compounds such as acenaphthene/fluorene nd phenanthrene. Various lines of evidence indicate that PAHs detected in above ground plant parts are chiefly derived from atmospheric inputs, while PAHs detected in root crops probably arise from adsorption to the root surface.
Levels and Patterns of Objectively Assessed Physical Activity and Compliance with Different Public Health Guidelines in University Students

Background Physical activity (PA) is associated with health enhancement. The aim of this study was to assess: 1) levels and patterns of PA in university students by using accelerometers; and 2) the percentage of fulfilment of PA recommendations for adults, according to different public health guidelines. Methods Observational cross-sectional study (Cuenca’s Adults Study) involving 296 (206 women) healthy Spanish university students aged 18–25 years old. Participants wore the ActiGraph GT1M accelerometer for seven consecutive days. Total PA, steps and time spent in sedentary time, light, moderate, vigorous, and moderate to vigorous PA (MVPA) was assessed, and the prevalence of sufficient PA was calculated according to various public health guidelines. Results No sex differences in total PA were found. University students were more sedentary during weekend days than weekdays (p<0.05). Only 30.3% of participants accumulated 30 min/day at least five days a week of MVPA. A total of 5.4% of students met the recommendation of 150 min/week of MVPA or 75 min/week of vigorous PA, in PA bouts of at least 10 min. using the same definition, but on five or more days a week, only 0.5% students were found to meet the recommendation. In addition, only 0.5% of students met the recommendation of 30 min/day of MVPA, at least five days a week and in bouts of at least 10 min. Finally, 28.1% of the students met the recommendation of 10,000 steps/day. Conclusions Our study shows a high incidence of sedentary time in university students. The number of students meeting PA recommendations significantly differed depending on the recommendation proposed. Specific strategies to promote PA in this population are necessary as well as an agreement as to which PA guidelines should be used.
Youth Culture and Smoking: Integrating Social Group Processes and Individual Cognitive Processes in a Model of Health-related Behaviours

This article assesses four theoretical models proposed to predict future smoking. Young adults were surveyed at three six-month intervals, the first occurring three months after leaving school. Models 1 and 2 were versions of theory of triadic influence (TTI), which links a person’s behavioural experience and cognitions to their future behaviour. Model 1 did not fit the data; the fit of model 2 was just adequate. Model 3 combined TTI and self-categorization theory (ST), by allowing norms of the individual’s peer group to influence cognitions and future behaviour. It fitted the data well. Model 4, which extended model, provided the best fit. Strength of identification to the peer group was found to enhance the effect of the peer group norm.
Residual Viremia in Treated HIV+ Individuals

Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. However, some residual virus remains, below the level of detection, in HIV-infected patients on ART. The source of this viremia is an area of debate: does it derive primarily from activation of infected cells in the latent reservoir, or from ongoing viral replication? Observations seem to be contradictory: there is evidence of short term evolution, implying that there must be ongoing viral replication, and viral strains should thus evolve. However, phylogenetic analyses, and rare emergent drug resistance, suggest no long-term viral evolution, implying that virus derived from activated latent cells must dominate. We use simple deterministic and stochastic models to gain insight into residual viremia dynamics in HIV-infected patients. Our modeling relies on two underlying assumptions for patients on suppressive ART: that latent cell activation drives viral dynamics and that the reproductive ratio of treated infection is less than 1. Nonetheless, the contribution of viral replication to residual viremia in patients on ART may be non-negligible. However, even if the portion of viremia attributable to viral replication is significant, our model predicts (1) that latent reservoir re-seeding remains negligible, and (2) some short-term viral evolution is permitted, but long-term evolution can still be limited: stochastic analysis of our model shows that de novo emergence of drug resistance is rare. Thus, our simple models reconcile the seemingly contradictory observations on residual viremia and, with relatively few parameters, recapitulates HIV viral dynamics observed in patients on suppressive therapy.
Evidence that major 78-44-kD concanavalin A-binding glycopolypeptides in pig epidermis arise from the degradation of desmosomal glycoproteins during terminal differentiation

The major concanavalin A (Con A)-binding component in urea/deoxycholate/mercaptoethanol extracts from pig ear epidermis had an apparent Mr of 78 kD. In indirect immunofluorescence affinity- purified polyclonal antibodies against this glycopolypeptide strongly stained the surface of suprabasal cells in the epidermis of pig and human skin. Immunocytochemical labeling with gold-labeled second antibody localized this staining to externally disposed, trypsin- sensitive components of desmosomes. Western blotting showed that the 78- kD glycopolypeptide was immunologically related to several other Con A- binding components in pig epidermis. Immunoreactive components with Mr of 115 and 100 kD were membrane-bound, appeared to be susceptible to trypsin in intact epidermis, and were absent from the stratum corneum. Immunoreactive components of lower Mr (78-44 kD) were not membrane- bound, were resistant to trypsin in intact tissue, and were present predominantly in the keratinized layers of pig epidermis. The 115-44-kD glycopolypeptides were also recognized by antisera raised against desmoglein II/desmocollin glycoproteins isolated from bovine spinous layer desmosomes. In addition, these antisera reacted with 120- and 105- kD bands that were apparently not recognized by the anti-78-kD glycopolypeptide antiserum in immunoblotting. In immune precipitation the anti-78-kD glycopolypeptide and antidesmoglein II/desmocollin antisera precipitated comparable amounts of the radioiodinated 78-44-kD components. Both antisera also precipitated the 120- and 105-kD components although the anti-78-kD glycopolypeptide serum was less effective. Little reaction with the 115- and 105-kD components was observed in immune precipitation with either serum. Proteolytic peptide mapping confirmed that the various immunoreactive glycopolypeptides were biochemically as well as immunologically related. The results suggest that terminal differentiation in pig epidermis is accompanied by the orderly degradation of desmoglein II/desmocollin glycoproteins resulting in the accumulation of 78-44-kD glycopolypeptides in the stratum corneum. These glycopolypeptides may represent functionally important nonmembranous domains of cell-adhesion molecules in desmosomes.
Nondestructive evaluation of low carbon steel by magnetic adaptive testing

Three series of low carbon steel samples, plastically deformed by cold rolling to five consecutive stages of deformation, were investigated by the method of magnetic adaptive testing (MAT), typical by its low required magnetisation of samples. Samples in one series were magnetically closed; those in the other two series were magnetically open. Results of the nondestructive magnetic tests were compared with the results of destructive mechanical measurements of Vickers hardness and ductile–brittle transition temperature. Linear, sensitive correlation with low scatter of values was found between the magnetic and the two mechanical parameters for any shape of the investigated specimens. Based on these results, MAT is suggested as a highly promising nondestructive alternative of destructive Charpy impact tests for monitoring the irradiation embrittlement of surveillance samples in pressure vessels of nuclear reactors.
Donnan phenomena in membranes with charge due to ion adsorption. Effects of the interaction between adsorbed charged groups

A physical model for the modified Donnan phenomenon associated with ion adsorption on localized membrane sites is presented. This model accounts for the dependence of the concentration of adsorbed ions on electrolyte concentration and pH as it is influenced by the electrostatic interaction between adsorbed ions. The equilibrium thermodynamic concepts employed are based on the Donnan formalism for the ion equilibria between membrane and solution, and the Bragg–Williams approximation for an adsorption isotherm that incorported interaction between adsorbed ions. Our results include the concentration of charged groups in the membrane, the pH of the membrane phase solution, and the Donnan potential as functions of the pH and the electrolyte concentration of the external solution for different degrees of the electrostatic interaction. These magnitudes are of considerable interest in biopolymers, membranes, and conducting polymers.
The Role of Human Hepatic Cytochrome P450 Isozymes in the Metabolism of Racemic 3,4-Methylenedioxyethylamphetamine and Its Single Enantiomers

The 3,4-methylenedioxy-methamphetamine (MDMA)-related designer drug 3,4-methylenedioxyethylamphetamine (MDEA, Eve) is a chiral compound that is mainly metabolized by N-deethylation and demethylenation during phase I metabolism. The involvement of several cytochrome P450 (P450) isozymes in these metabolic steps has been demonstrated by inhibition assays using human liver microsomes. However, a comprehensive study on the involvement of all relevant human P450s has not been published yet. In addition, the chirality of this drug was not considered in these in vitro studies. The aim of the present work was first to elucidate the contribution of the relevant human P450 isozymes in the demethylenation as well as in the N-dealkylation of racemic MDEA and its single enantiomers and secondly to compare these findings with recently published data concerning the enantioselective metabolism of MDMA. Racemic MDEA and its single enantiomers were incubated using heterologously expressed human P450s, and the corresponding metabolites dihydroxyethylamphetamine and methylenedioxyamphetamine were determined by gas chromatography-mass spectrometry after chiral derivatization with S-heptafluorobutyrylprolyl chloride. The highest contributions to both metabolic steps as calculated from the enzyme kinetic data were obtained for CYP3A4 and CYP2D6 at substrate concentrations corresponding to plasma concentrations of recreational users after intake of racemic MDEA. Both metabolic reactions were found to be enantioselective with a general preference for the S-enantiomers, which was particularly pronounced in the case of CYP2C19. In conclusion, different pharmacokinetic properties of MDEA enantiomers observed in vivo are therefore partially caused by P450-dependent enantioselective metabolism.
Dominant negative c-Src inhibits angiotensin II induced activation of NHE3 in OKP cells.

BACKGROUND Angiotensin II is a potent stimulator of the proximal tubule apical membrane Na/H antiporter, encoded by NHE3. The nonreceptor tyrosine kinase, c-Src, plays a key role in regulation of NHE3 by acidosis in the proximal tubule, and in signaling effects of angiotensin II in vascular smooth muscle. METHODS The present studies examined the role of c-Src in mediating angiotensin II-induced NHE3 activation in cultured OKP cells. c-Src was inhibited with herbimycin A, a tyrosine kinase inhibitor, and expression of a dominant negative c-Src, c-SrcK295M. RESULTS Herbimycin A blocked angiotensin II induced increases in Na/H antiporter activity. In two clonal cell lines expressing vector alone, angiotensin II increased Na/H antiporter activity, while in three clones expressing c-SrcK295M, angiotensin II had no effect. Cyclic AMP and protein kinase A have been proposed to be key mediators in regulation of NHE3 by angiotensin II. 10(-4) M 8-bromo cAMP induced a 40 to 50% inhibition of Na/H antiporter activity in cells expressing c-SrcK295M, similar to that seen in wild-type OKP cells. In addition, cells expressing c-SrcK295M responded normally to 10(-7) M dexamethasone with a 50 to 80% increase in Na/H antiporter activity. CONCLUSIONS These studies demonstrate that c-Src is required for angiotensin II-induced increases in NHE3 activity. Thus, c-Src plays a key role in antiporter activation by acidosis and angiotensin II.