Miracle-dz/UniFAR-FTUs huggingface dataset:
Potent suppression of both spontaneous and carcinogen-induced colitis-associated colorectal cancer in mice by dietary celastrol supplementation

Celastrol is an anti-inflammatory natural triterpenoid, isolated from the herb Tripterygium wilfordii or thunder god vine. Here, we define mechanisms mediating anti-inflammatory activity of celastrol and demonstrate efficacy of a dietary celastrol supplement for chemoprevention of inflammation-driven carcinogenesis in mice. Dietary celastrol (31.25 ppm in rodent diet from 8 weeks to 25 weeks of age) is well tolerated and protects against LPS-induced acute inflammation in C57BL/6 mice, potently suppressing LPS-induction of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, Interleukin (IL)-6 and IL-1β. To test whether dietary celastrol suppresses inflammation-driven colorectal cancer (CRC), we employed a unique model of spontaneous, inflammation-driven CRC in mice harboring a germ line deletion of the p27Kip1 gene and a T cell-specific deletion of Smad4 gene (Smad4co/co;Lck-crep27Kip1-/-or DKO), which develop severe intestinal inflammation and carcinogenesis as early as 3 months of age. Exposure of DKO mice to daily dietary celastrol (12.5 ppm in diet) from 6 weeks of age significantly suppressed development of colitis-associated CRC (CAC). Celastrol chemoprevention of CAC in this new model of intestinal neoplasia was associated with significant suppression of iNOS at 4 months of age, and iNOS, COX-2 and NFκB at 6 months of age, with significant reduction in inflammatory cytokines, IL-6 and IL-1β. Chemoprevetion of CAC by dietary celastrol was further confirmed in the model of azoxymethane (AOM) plus dextran sodium sulfate (DSS)-induced carcinogenesis in C57BL/6 mice. These data suggest the potential for celastrol as a safe and effective dietary supplement in the chemoprevention of CAC in humans.
Dysregulation of Mitochondrial Quality Control Processes Contribute to Sarcopenia in a Mouse Model of Premature Aging

Mitochondrial DNA (mtDNA) mutations lead to decrements in mitochondrial function and accelerated rates of these mutations has been linked to skeletal muscle loss (sarcopenia). The purpose of this study was to investigate the effect of mtDNA mutations on mitochondrial quality control processes in skeletal muscle from animals (young; 3–6 months and older; 8–15 months) expressing a proofreading-deficient version of mtDNA polymerase gamma (PolG). This progeroid aging model exhibits elevated mtDNA mutation rates, mitochondrial dysfunction, and a premature aging phenotype that includes sarcopenia. We found increased expression of the mitochondrial biogenesis regulator peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and its target proteins, nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (Tfam) in PolG animals compared to wild-type (WT) (P<0.05). Muscle from older PolG animals displayed higher mitochondrial fission protein 1 (Fis1) concurrent with greater induction of autophagy, as indicated by changes in Atg5 and p62 protein content (P<0.05). Additionally, levels of the Tom22 import protein were higher in PolG animals when compared to WT (P<0.05). In contrast, muscle from normally-aged animals exhibited a distinctly different expression profile compared to PolG animals. Older WT animals appeared to have higher fusion (greater Mfn1/Mfn2, and lower Fis1) and lower autophagy (Beclin-1 and p62) compared to young WT suggesting that autophagy is impaired in aging muscle. In conclusion, muscle from mtDNA mutator mice display higher mitochondrial fission and autophagy levels that likely contribute to the sarcopenic phenotype observed in premature aging and this differs from the response observed in normally-aged muscle.
Face and Object Perception in Body Dysmorphic Disorder versus Obsessive-Compulsive Disorder: The Mooney Faces Task

Abstract Objectives: Body dysmorphic disorder (BDD) is characterized by repetitive behaviors and/or mental acts occurring in response to preoccupations with perceived defects or flaws in physical appearance. There are some similarities, but also important differences, between BDD and obsessive-compulsive disorder (OCD), not just in terms of core clinical symptoms, but possibly in the domain of perception. This study compared the nature and extent of perceptual anomalies in BDD versus OCD and health controls (HC), using a modified Mooney task. Methods: We included 21 BDD, 19 OCD, and 21 HC participants, who were age-, sex-, and IQ-matched. A set of 40 Mooney faces and 40 Mooney objects arranged in three configurations (i.e., upright, inverted, or scrambled) were presented under brief (i.e., 500 ms) free-viewing conditions. Participants were asked to decide whether each image represented a human face, an object, or neither in a forced-choice paradigm. Results: The BDD group showed significantly reduced face and object inversion effects relative to the other two groups. This was accounted for by BDD participants being significantly more accurate in identifying inverted Mooney faces and objects than the other participants. Conclusions: These data were interpreted as reflecting an overreliance on independent components at the expense of holistic (configural) processing in BDD. (JINS, 2017, 23, 471–480)
An increase in dietary carotenoids when consuming plant sterols or stanols is effective in maintaining plasma carotenoid concentrations.

BACKGROUND Plant-sterol-enriched spreads lower LDL cholesterol but may also lower lipid-standardized carotenoids. OBJECTIVE Our objective was to assess whether advice to consume specific daily amounts of foods high in carotenoids prevents a reduction in plasma carotenoid concentrations in subjects who consume plant sterol or stanol esters. DESIGN Forty-six hypercholesterolemic free-living subjects completed a 3-way, double-blind, randomized crossover comparison. Subjects consumed each of the following 3 spreads (25 g/d) for 3 wk: control-1 (sterol-free), sterol ester-1 (2.3 g plant sterol esters), and stanol ester-1 (2.5 g plant stanol esters). During the 3-wk interventions, subjects were advised to eat > or =5 servings of vegetables and fruit/d, of which > or =1 serving was to be carrots, sweet potatoes, pumpkins, tomatoes, apricots, spinach, or broccoli. RESULTS The dietary advice resulted in a 13% increase in plasma beta-carotene in subjects who consumed control-1 (P = 0.04). The plasma beta-carotene concentrations of subjects who consumed control-1 did not differ significantly from those of subjects who consumed stanol ester-1 or sterol ester-1. This result was achieved by an increase of one daily serving of high-carotenoid vegetables or fruit. LDL cholesterol decreased 7.7% and 9.5% after consumption of sterol ester-1 and stanol ester-1, respectively (P < 0.001 for both), and differences between the LDL-cholesterol values obtained were not significant. CONCLUSION Dietary advice to consume an additional daily serving of a high-carotenoid vegetable or fruit when consuming spreads containing sterol or stanol esters maintains plasma carotenoid concentrations while lowering LDL-cholesterol concentrations significantly.
Photothermal Determination of Absorption and Scattering Spectra of Silver Nanoparticles

This work reports on photothermal lens spectra of silver nanoparticles of different dimensions in the spectral region of 370–730 nm performed using an arc-lamp-based photothermal spectrophotometer. We show that the photothermal and extinction cross-section spectra of the samples are similar for nanoparticles of reduced dimensions where scattering effects are small. The results differ substantially for nanoparticles of a diameter larger than 30 nm for which scattering becomes relevant. We demonstrate that the photothermal spectrum corresponds to the absorption component of the particle’s extinction. Photothermal spectra show a clear picture of the plasmonic peaks of the nanoparticle even in the presence of high scattering. By subtracting the photothermal component from the total extinction, we extract the scattering cross-section spectra of the nanoparticles. The technique allows determination of the absorption and scattering components of the extinction providing a better understanding of the particle’s optical properties. The results agree well with the Mie approximation, which is valid for a single spherical nanoparticle. We discuss and demonstrate the application of the method to characterize particles of arbitrary shape and dimensions.
Circadian rhythms identified in Caenorhabditis elegans by in vivo long-term monitoring of a bioluminescent reporter

Significance Endogenous circadian rhythms have been demonstrated in several model systems, including mammals, insects, and fungi, among many others. Cycles in behavior, physiology and gene expression have also been reported in the nematode Caenorhabditis elegans, although limited by experimental conditions. Here we report the application of a luciferase-based reporter to investigate circadian regulation in C. elegans. Our study demonstrates entrainable, endogenous, and temperature-dependent circadian rhythms in gene expression as well as part of the pathway for synchronization. Our results represent an innovative approach for the study of long-term gene expression in real time in this system, opening the way for novel research in neuroscience and molecular pathways in general, including the precise determination of its elusive circadian clock. Circadian rhythms are based on endogenous clocks that allow organisms to adjust their physiology and behavior by entrainment to the solar day and, in turn, to select the optimal times for most biological variables. Diverse model systems—including mice, flies, fungi, plants, and bacteria—have provided important insights into the mechanisms of circadian rhythmicity. However, the general principles that govern the circadian clock of Caenorhabditis elegans have remained largely elusive. Here we report robust molecular circadian rhythms in C. elegans recorded with a bioluminescence assay in vivo and demonstrate the main features of the circadian system of the nematode. By constructing a luciferase-based reporter coupled to the promoter of the suppressor of activated let-60 Ras (sur-5) gene, we show in both population and single-nematode assays that C. elegans expresses ∼24-h rhythms that can be entrained by light/dark and temperature cycles. We provide evidence that these rhythms are temperature-compensated and can be re-entrained after phase changes of the synchronizing agents. In addition, we demonstrate that light and temperature sensing requires the photoreceptors LITE and GUR-3, and the cyclic nucleotide-gated channel subunit TAX-2. Our results shed light on C. elegans circadian biology and demonstrate evolutionarily conserved features in the circadian system of the nematode.
The Trace Amine-Associated Receptor 1 Agonist 3-Iodothyronamine Induces Biased Signaling at the Serotonin 1b Receptor

Trace amine-associated receptors (TAARs) belong to the class A G-protein-coupled receptors (GPCR) and are evolutionary related to aminergic receptors. TAARs have been identified to mediate effects of trace amines. TAAR1 signaling is mainly mediated via activation of the Gs/adenylyl cyclase pathway. In addition to classical trace amines, TAAR1 can also be activated by the thyroid hormone derivative 3-iodothyronamine (3-T1AM). Pharmacological doses of 3-T1AM induced metabolic and anapyrexic effects, which might be centrally mediated in the hypothalamus in rodents. However, the observed anapyrexic effect of 3-T1AM persists in Taar1 knock-out mice which raises the question whether further GPCRs are potential targets for 3-T1AM and mediate the observed physiological effect. Anapyrexia has been observed to be related to action on aminergic receptors such as the serotonin receptor 1b (5-HT1b). This receptor primarily activates the Gi/o mediated pathway and PLC signaling through the Gβγ of Gi/o. Since the expression profiles of TAAR1 and 5-HT1b overlap, we questioned whether 3-T1AM may activate 5-HT1b. Finally, we also evaluated heteromerization between these two GPCRs and tested signaling under co-expressed conditions. In this study, we showed, that 3-T1AM can induce Gi/o signaling through 5-HT1b in a concentration of 10 μM. Strikingly, at 5-HT1b the ligand 3-T1AM only activates the Gi/o mediated reduction of cAMP accumulation, but not PLC activation. Co-stimulation of 5-HT1b by both ligands did not lead to additive or synergistic signaling effects. In addition, we confirmed the capacity for heteromerization between TAAR1 and 5-HT1b. Under co-expression of TAAR1 and HTR1b, 3-T1AM action is only mediated via TAAR1 and activation of 5-HT1b is abrogated. In conclusion, we found evidence for 5-HT1b as a new receptor target for 3-T1AM, albeit with a different signaling effect than the endogenous ligand. Altogether, this indicates a complex interrelation of signaling effects between the investigated GPCRs and respective ligands.
Respiratory modulation of human autonomic function on Earth

We studied healthy supine astronauts on Earth with electrocardiogram, non‐invasive arterial pressure, respiratory carbon dioxide concentrations, breathing depth and sympathetic nerve recordings. The null hypotheses were that heart beat interval fluctuations at usual breathing frequencies are baroreflex mediated, that they persist during apnoea, and that autonomic responses to apnoea result from changes of chemoreceptor, baroreceptor or lung stretch receptor inputs. R‐R interval fluctuations at usual breathing frequencies are unlikely to be baroreflex mediated, and disappear during apnoea. The subjects’ responses to apnoea could not be attributed to changes of central chemoreceptor activity (hypocapnia prevailed); altered arterial baroreceptor input (vagal baroreflex gain declined and muscle sympathetic nerve burst areas, frequencies and probabilities increased, even as arterial pressure climbed to new levels); or altered pulmonary stretch receptor activity (major breathing frequency and tidal volume changes did not alter vagal tone or sympathetic activity). Apnoea responses of healthy subjects may result from changes of central respiratory motoneurone activity.
Political Ideology, Trust, and Cooperation

Theories suggest that political ideology relates to cooperation, with conservatives being more likely to pursue selfish outcomes, and liberals more likely to pursue egalitarian outcomes. In study 1, we examine how political ideology and political party affiliation (Republican vs. Democrat) predict cooperation with a partner who self-identifies as Republican or Democrat in two samples before (n = 362) and after (n = 366) the 2012 US presidential election. Liberals show slightly more concern for their partners’ outcomes compared to conservatives (study 1), and in study 2 this relation is supported by a meta-analysis (r = .15). However, in study 1, political ideology did not relate to cooperation in general. Both Republicans and Democrats extend more cooperation to their in-group relative to the out-group, and this is explained by expectations of cooperation from in-group versus out-group members. We discuss the relation between political ideology and cooperation within and between groups.
An Extra Amino Acid Residue in Transmembrane Domain 10 of the γ-Aminobutyric Acid (GABA) Transporter GAT-1 Is Required for Efficient Ion-coupled Transport*

The GABA transporter GAT-1 mediates electrogenic transport of its substrate together with sodium and chloride. It is a member of the neurotransmitter:sodium:symporters, which are crucial for synaptic transmission. Compared with all other neurotransmitter:sodium:symporters, GAT-1 and other members of the GABA transporter subfamily all contain an extra amino acid residue at or near a conserved glycine in transmembrane segment 10. Therefore, we studied the functional impact of deletion and replacement mutants of Gly-457 and its two adjacent residues in GAT-1. The glycine replacement mutants were devoid of transport activity, but remarkably the deletion mutant was active, as were mutants obtained by deleting positions on either side of Gly-457. However, the inward rectification of GABA-induced transport currents by all three deletion mutants was diminished, and the charge-to-flux ratio was increased by more than 2.5-fold, both of which indicate substantial uncoupled transport. These observations suggest that the deletions render the transporters less tightly packed. Consistent with this interpretation, the inactive G457A mutant was partially rescued by removing the adjacent serine residue. Moreover, the activity of several gating mutants was also partially rescued upon deletion of Gly-457. Structural modeling showed that the stretch surrounding Gly-457 is likely to form a π-helix. Our data indicate that the “extra” residue in transmembrane domain 10 of the GABA transporter GAT-1 provides extra bulk, probably in the form of a π-helix, which is required for stringent gating and tight coupling of ion and substrate fluxes in the GABA transporter family.
Causes and outcomes of markedly elevated C-reactive protein levels.

OBJECTIVE To characterize the causes of marked elevation of C-reactive protein (CRP) levels, investigate patient outcomes, and examine factors that might influence the CRP response. DESIGN Health records were used to retrospectively determine patient characteristics, diagnoses, and outcomes over a 2-year period (2012 to 2013). SETTING A large referral centre in Moncton, NB. PARTICIPANTS Adult inpatients and outpatients with a CRP level above 100 mg/L. MAIN OUTCOME MEASURES Differences among the CRP distributions of various diagnosis categories were examined using Kruskal-Wallis tests, and factors affecting outcomes were examined using Fisher exact tests. RESULTS Over the 2-year period, 1260 CRP levels (839 patients; 3.1% of all tests) were above 100 mg/L (range 100.1 to 576.0 mg/L). The mean age was 63 years (range 18 to 101) and 50.2% of patients were men. Infection was the most prevalent cause (55.1%), followed by rheumatologic diseases (7.5%), multiple causes (5.6%), other inflammatory conditions (5.4%), malignancy (5.1%), drug reactions (1.7%), and other conditions (2.0%). A diagnosis could not be established in 17.6% of cases. On average, infections caused higher peak CRP levels (W = 34 519, P < .001) and infection was present in 88.9% of cases with CRP levels greater than 350 mg/L. Rheumatologic causes were associated with only 5.6% of CRP levels above 250 mg/L. The overall mortality was 8.6% and was higher in patients with malignancy (37.0%), multiple diagnoses (21.0%), and leukopenia (20.7%, P = .002). CONCLUSION Most patients had infections and the proportion of patients with infections increased with the level of CRP, although many diagnoses were associated with markedly elevated CRP levels. These data could help guide health care professionals in the evaluation and management of these patients.
Processing of Al2O3-Y-PSZ Laminated Ceramic Composites

Laminated ceramic composites (LCCs) were made by stacking layers with specific compositions in a predetermined sequence to achieve desired physical or mechanical properties. In the present work, the aim was to optimize the different processing parameters for fabricating AI2O3-ZrO2 laminated composites. With this aim, composites with different layer thicknesses, starting from 2 mm and going down to 0.3 mm, were made by hot pressing. The different types of cracks originating in the composites were studied in detail and the reasons behind their formation were analyzed. The main reasons for crack formation were found to be: (i) different shrinkage in between the co-sintering layers due to their different sintering kinetics, (ii) thermal expansion mismatch and (iii) a tensile component of the residual stress in the layer under residual compression. Suitable remedial measures were taken to avoid the crack formation and a laminated composite with 15 layers of 0.3 mm thickness was fabricated.
Has the American Public’s Interest in Information Related to Relationships Beyond “The Couple” Increased Over Time?

Finding romance, love, and sexual intimacy is a central part of our life experience. Although people engage in romance in a variety of ways, alternatives to “the couple” are largely overlooked in relationship research. Scholars and the media have recently argued that the rules of romance are changing, suggesting that interest in consensual departures from monogamy may become popular as people navigate their long-term coupling. This study utilizes Google Trends to assess Americans’ interest in seeking out information related to consensual nonmonogamous relationships across a 10-year period (2006–2015). Using anonymous Web queries from hundreds of thousands of Google search engine users, results show that searches for words related to polyamory and open relationships (but not swinging) have significantly increased over time. Moreover, the magnitude of the correlation between consensual nonmonogamy Web queries and time was significantly higher than popular Web queries over the same time period, indicating this pattern of increased interest in polyamory and open relationships is unique. Future research avenues for incorporating consensual nonmonogamous relationships into relationship science are discussed.
Intermittent Ca2+ signals mediated by Orai1 regulate basal T cell motility

Ca2+ influx through Orai1 channels is crucial for several T cell functions, but a role in regulating basal cellular motility has not been described. Here we show that inhibition of Orai1 channel activity increases average cell velocities by reducing the frequency of pauses in human T cells migrating through confined spaces, even in the absence of extrinsic cell contacts or antigen recognition. Utilizing a novel ratiometric genetically encoded cytosolic Ca2+ indicator, Salsa6f, which permits real-time monitoring of cytosolic Ca2+ along with cell motility, we show that spontaneous pauses during T cell motility in vitro and in vivo coincide with episodes of cytosolic Ca2+ signaling. Furthermore, lymph node T cells exhibited two types of spontaneous Ca2+ transients: short-duration “sparkles” and longer duration global signals. Our results demonstrate that spontaneous and self-peptide MHC-dependent activation of Orai1 ensures random walk behavior in T cells to optimize immune surveillance.
A Validation Study of an Interviewer-Administered Short Food Frequency Questionnaire in Assessing Dietary Vitamin D and Calcium Intake in Swedish Children

Vitamin D and calcium are essential nutrients with a range of biological effects of public health relevance. This study aimed to validate a short food frequency questionnaire (SFFQ) against a three-day food record (3D record), assessing the intake of vitamin D and calcium in Swedish children during wintertime. In a double-blinded, randomized food-based intervention study on the effect of feeding different daily doses of vitamin D supplement to 5–7-year-old children (n = 85), 79 (93%) participants completed SFFQ1 at baseline and SFFQ2 after the intervention, and 72 were informed to fill in a 3D record. The 28 (39%) children who completed the 3D record were included in this validation study. The baseline level of serum-25 hydroxy vitamin D [S-25(OH)D] was used as a biomarker. The correlation between all three instruments were moderate to strong. SFFQ2 and the 3D record correlated moderately to S-25(OH)D. Bland-Altman analysis showed that SFFQ2 overestimated vitamin D intake by on average 0.6 μg/day, (limits of agreement (LOA) 5.7 and −4.6 μg/day), whereas the intake of calcium was underestimated by on average 29 mg/day, (LOA 808 and −865 mg/day). Finally, the validity coefficient calculated for vitamin D using the method of triad was high (0.75). In conclusion, this SFFQ, assessed by a dietician, is a valid tool to assess dietary vitamin D and calcium intake in groups of young children.