Miracle-dz/UniFAR-FTUs huggingface dataset:
Positional Distribution of Fatty Acids in Triacylglycerols and Phospholipids from Fillets of Atlantic Salmon (Salmo Salar) Fed Vegetable and Fish Oil Blends

The nutritional and functional characteristics of dietary fat are related to the fatty acid (FA) composition and its positional distribution in the triacylglycerol (TAG) fraction. Atlantic salmon is an important source of healthy long chain omega 3 FA (particularly, eicosapentaenoic (EPA) and docoxahexaenoic (DHA) acids). However, the impact of lipid sources in salmon feeds on the regiospecificity of FA in the fish TAG remains to be explored. The present study determines the effect of feeding salmon with blends of palm, rapeseed, and fish oil, providing two different EPA + DHA concentrations (high: H-ED 10.3% and low: L-ED 4.6%) on the fillet lipid class composition and the positional distribution of FA in TAG and phospholipids. The regiospecific analysis of fillet TAG showed that around 50% of the EPA and around 80% of DHA was located in the sn-2 position. The positional distribution of FA in phosphatidylcholine (PC), showed that around 80% of the EPA and around 90% of DHA were located in the sn-2. Fish fed the vegetable-rich diets showed higher EPA in the sn-2 position in PC (77% vs. 83% in the H-ED and L-ED diets, respectively) but similar DHA concentrations. It is concluded that feeding salmon with different EPA + DHA concentrations does not affect their positional distribution in the fillet TAG.
TCA cycle‐independent acetate metabolism via the glyoxylate cycle in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, the accepted theory is that due to TCA cycle dysfunction, the Δcit1 mutant lacking the mitochondrial enzyme citrate synthase (Cit1) cannot grow on acetate, regardless of the presence of the peroxisomal isoenzyme (Cit2). In this study, we re‐evaluated the roles of Cit1 and Cit2 in acetate utilization and examined the pathway of acetate metabolism by analysing mutants defective in TCA or glyoxylate cycle enzymes. Although Δcit1 cells showed significantly reduced growth on rich acetate medium (YPA), they exhibited growth similar to Δcit2 and the wild‐type cells on minimal acetate medium (YNBA). Impaired acetate utilization by Δcit1Δcit2 cells on YNBA was restored by ectopic expression of either Cit2 or its cytoplasmically localized variants. Deletion of any of the genes for the enzymes solely involved in the TCA cycle (IDH1, KGD1 and LSC1), except for SDH1, caused little defect in acetate utilization on YNBA but resulted in significant growth impairment on YPA. In contrast, cells lacking any of the genes involved in the glyoxylate cycle (ACO1, FUM1, MLS1, ICL1 and MDH2) did not grow on either YNBA or YPA. Deletion of SFC1 encoding the succinate–fumarate carrier also caused similar growth defects on YNBA. Our results suggest that in S. cerevisiae the glyoxylate cycle functions as a competent metabolic pathway for acetate utilization on YNBA, while both the TCA and glyoxylate cycles are essential for growth on YPA. Copyright © 2010 John Wiley & Sons, Ltd.
Dynamic Choice Under Ambiguity

This paper analyzes sophisticated dynamic choice for ambiguity-sensitive decision makers. It characterizes Consistent Planning via axioms on preferences over decision trees. Furthermore, it shows how to elicit conditional preferences from prior preferences. The key axiom is a weakening of Dynamic Consistency, deemed Sophistication. The analysis accommodates arbitrary decision models and updating rules. Hence, the results indicate that (i) ambiguity attitudes, (ii) updating rules, and (iii) sophisticated dynamic choice are mutually orthogonal aspects of preferences. As an example, a characterization of prior-by-prior Bayesian updating and Consistent Planning for arbitrary maxmin-expected utility preferences is presented. The resulting sophisticated MEU preferences are then used to analyze the value of information under ambiguity; a basic trade-off between information acquisition and commitment is highlighted.
An abnormal gene expression of the β‐adrenergic system contributes to the pathogenesis of cardiomyopathy in cirrhotic rats

Decreased cardiac contractility and β‐adrenergic responsiveness have been observed in cirrhotic cardiomyopathy, but their molecular mechanisms remain unclear. To study β‐adrenergic–stimulated contractility and β‐adrenergic gene expression patterns, 20 Wistar Kyoto rats were treated with carbon tetrachloride to induce cirrhosis and 20 rats were used as controls. Left ventricular contractility was recorded in electrically driven isolated hearts perfused at constant flow with isoproterenol (10−10 to 10−6 M). A cardiac gene expression profile was obtained using a microarray for the myocyte adrenergic pathway. The cardiac contractility maximal response to isoproterenol was significantly reduced in cirrhotic rats in comparison to control rats, whereas the half‐maximal effective concentration was not different. In cirrhotic rats, cardiac gene expression analysis showed a significant overexpression of G protein alpha–inhibiting subunit 2 (Gαi2), cyclic nucleotide phosphodiesterase (PDE2a), regulator of G‐protein signaling 2 (RGS2), and down‐expression of adenylate cyclase (Adcy3). These results indicate that overexpression of Gαi2, PDE2a, and RGS2 down‐regulates the β‐adrenergic signaling pathway, thus contributing to the pathogenesis of cirrhotic cardiomyopathy. (HEPATOLOGY 2008;48:1913‐1923.)
Docosahexaenoic acid up‐regulates both PI3K/AKT‐dependent FABP7–PPARγ interaction and MKP3 that enhance GFAP in developing rat brain astrocytes

The astrocyte marker, glial fibrillary acidic protein (GFAP), has essential functions in the brain, but may trigger astroglial scarring when expressed in excess. Docosahexaenoic acid (DHA) is an n‐3 fatty acid that is protective during brain development. However, the effect of DHA on GFAP levels of developing brain remains unexplored. Here, we detected that treating developing rats with DHA‐enriched fish‐oil caused dose‐dependent GFAP augmentation. We investigated the mechanism promoting GFAP, hypothesizing the participation of fatty acid‐binding protein‐7 (FABP7), known to bind DHA. We identified that DHA stimulated FABP7 expression in astrocytes, and FABP7‐silencing suppressed DHA‐induced GFAP, indicating FABP7‐mediated GFAP increase. Further investigation proved FABP7 expression to be phosphatidylinositide 3‐kinases (PI3K)/AKT and nuclear receptor peroxisome proliferator‐activated receptor‐gamma (PPARγ)‐dependent. We found that PI3K/AKT activated PPARγ that triggered FABP7 expression via PPARγ‐responsive elements within its gene. Towards identifying FABP7‐downstream pathways, we considered our previous report that demonstrated cyclin‐dependent kinase‐5 (CDK5)‐PPARγ‐protein–protein complex to suppress GFAP. We found that the DHA‐induced FABP7 underwent protein‐protein interaction with PPARγ, which impeded CDK5‐PPARγ formation. Hence, it appeared that enhanced FABP7‐PPARγ in lieu of CDK5‐PPARγ resulted in increased GFAP. PI3K/AKT not only stimulated formation of FABP7‐PPARγ protein‐protein complex, but also up‐regulated a FABP7‐independent MAP‐kinase‐phosphatase‐3 pathway that inactivated CDK5 and hence attenuated CDK5‐PPARγ. Overall, our data reveal that via the proximal PI3K/AKT, DHA induces FABP7‐PPARγ, through genomic and non‐genomic mechanisms, and MAP‐kinase‐phosphatase‐3 that converged at attenuated CDK5‐PPARγ and therefore, enhanced GFAP. Accordingly, our study demonstrates a DHA‐mediated astroglial hyperactivation, pointing toward a probable injurious role of DHA in brain development.
Superiority of Rapamycin Over Tacrolimus in Preserving Nonhuman Primate Treg Half‐Life and Phenotype After Adoptive Transfer

Many critical issues remain concerning how best to deploy adoptive regulatory T cell (Treg) immunotherapy to the clinic. These include a determination of their pharmacokinetic characteristics, their optimal dose, their phenotypic stability and the best therapies with which to pair Tregs. By performing a CFSE‐labeled autologous Treg pulse experiment, we determined that the accessible peripheral blood Treg pool in rhesus macaques is quite large (75 ± 11 × 106 Tregs/kg). Pharmacokinetic analysis revealed that Tregs have two phases of elimination: an α phase, with a T1/2 in the peripheral blood of 32.4 ± 11.3 h and a β phase with a T1/2 of 120.4 ± 19.7 h. In addition to their short initial half‐life, Tregs underwent rapid phenotypic shifts after infusion, with significant loss of both CD25 and FoxP3 by day +6. While tacrolimus stabilized CD25 expression, it did not improve T1/2, nor mitigate the loss of FoxP3. In contrast, rapamycin significantly stabilized both CD25 and FoxP3, and supported an increased half‐life, with an α phase of 67.7 ± 6.9 h and a β phase of 252.1 ± 54.9 h. These results suggest that rapamycin may be a necessary addition to Treg immunotherapy, and that tacrolimus may be deleterious to Treg integrity posttransfer.
Is cardiovascular disease a risk factor in the development of axonal polyneuropathy?

Objectives: To determine if cardiovascular disease may be a risk factor in the development of chronic idiopathic axonal polyneuropathy (CIAP). Methods: In this incidence case-control study, the prevalence of cardiovascular disease and risk factors in 97 patients with CIAP (mean age 67.5 (SD 7.9) years) and the prevalence of neuropathic features in 97 patients with peripheral arterial disease (PAD) (mean age 67.1 (SD 7.3) years) were investigated. The results were compared with those for 96 age and sex matched controls without diagnosed PAD or polyneuropathy (mean age 67.5 (SD 9.1) years). In a randomly chosen subgroup of 23 patients with CIAP, 42 patients with PAD, and 48 controls, an electrodiagnostic investigation was performed. Results: Patients with CIAP more often had manifest cardiovascular disease and cardiovascular risk factors than controls (stroke 18% v 6% of patients, odds ratio (OR) 3.2 (95% confidence interval (CI) 1.8 to 5.9); heart disease 29% v 15%, OR 2.4 (95% CI 1.2 to 4.9); family history of cardiovascular disease 42% v 21%, OR 2.8 (95% CI (1.5 to 5.2); hypertension 56% v 39%, OR 2.0 (95% CI 1.1 to 3.6); hypercholesterolaemia 46% v 21%, OR 3.3 (95% CI 1.5 to 7.3); current smoking 38% v 23%, OR 2.1 (95% CI 1.1 to 3.9)). The prevalence of cardiovascular disease and cardiovascular risk factors was lower than in patients with PAD. Patients with PAD more often had polyneuropathy than controls (15% v 5%, OR 3.3 (95% CI 1.1 to 10.0)). There was a trend towards lower nerve conduction velocities and lower amplitudes on electrodiagnostic investigation compared with controls. Conclusion: This study shows that cardiovascular disease and CIAP often coexist, and therefore cardiovascular disease may be a cofactor in the development of CIAP.
HYPERTONIC UREA IN EXPERIMENTAL CEREBRAL EDEMA.

Introduction THE EXPERIMENTS to be reported represent a further continuation in monkeys of work on cerebral injury originally begun in rabbits 11 and continued in dogs. 4 Our purpose in conducting these experiments has been to evaluate therapeutic measures designed to alleviate the effects of cerebral hemorrhage and edema. To this end, a method was devised of producing areas of hemorrhagic necrosis in the brains of experimental animals by freezing through the exposed intact skull. Quantitative methods were then devised to study the edema and hemorrhage through measurements of water and iron in the damaged tissue. 6 An attempt was then made to assess the effects of intravenous hypertonic solutions by means of these methods. Since these lesions were produced through the intact skull with preservation of intracranial fluid dynamics, changes in the cerebrospinal fluid pressure (CSFP) could also be studied. It was found that these lesions were associated
Biosynthesis of estrogens.

The formation of estrogens and phenolic material from a large number of do Cis, C19 and C2i steroids and related structures has been investigated, employing a human placental microsomal preparation supplemented with TPNH and oxygen. The data from the incubation of 2 C 14-labeled androgens are included. There is a discussion of possible biosynthetic pathways for the estrogens.
Ablation of ZnO in liquid by Nanosecond Laser

Zinc oxide (ZnO) was synthesized by laser ablation in liquid. The preparation steps included immersing ZnO bulk pellet in ethanol and then ablating by Nd-Yag laser. The used laser has a wavelength ranging from 1064 nm to 532 nm with 140 mJ pulse intensity. Structural, morphological and optical properties of the prepared material were investigated by X-ray diffraction, scanning electron microscopy and UV-Vis spectroscopy, respectively. The XRD results revealed the formation of hexagonal ZnO structure with (101) as dominant peak. The SEM studies demonstrated the formation of spherical ZnO nanoparticles which agglomerated to form nanocluster. Typical exciton absorption was observed at 376 nm in the absorption spectrum of UV-Vis spectroscopy at room temperature and the energy gap was equal to (3.48 eV).
The autism-linked UBE3A T485A mutant E3 ubiquitin ligase activates the Wnt/β-catenin pathway by inhibiting the proteasome

UBE3A is a HECT domain E3 ubiquitin ligase whose dysfunction is linked to autism, Angelman syndrome, and cancer. Recently, we characterized a de novo autism-linked UBE3A mutant (UBE3AT485A) that disrupts phosphorylation control of UBE3A activity. Through quantitative proteomics and reporter assays, we found that the UBE3AT485A protein ubiquitinates multiple proteasome subunits, reduces proteasome subunit abundance and activity, stabilizes nuclear β-catenin, and stimulates canonical Wnt signaling more effectively than wild-type UBE3A. We also found that UBE3AT485A activates Wnt signaling to a greater extent in cells with low levels of ongoing Wnt signaling, suggesting that cells with low basal Wnt activity are particularly vulnerable to UBE3AT485A mutation. Ligase-dead UBE3A did not stimulate Wnt pathway activation. Overexpression of several proteasome subunits reversed the effect of UBE3AT485A on Wnt signaling. We also observed that subunits that interact with UBE3A and affect Wnt signaling are located along one side of the 19S regulatory particle, indicating a previously unrecognized spatial organization to the proteasome. Altogether, our findings indicate that UBE3A regulates Wnt signaling in a cell context-dependent manner and that an autism-linked mutation exacerbates these signaling effects. Our study has broad implications for human disorders associated with UBE3A gain or loss of function and suggests that dysfunctional UBE3A might affect additional proteins and pathways that are sensitive to proteasome activity.
A Converse Lyapunov Theorem for Nonuniform in Time Global Asymptotic Stability and Its Application to Feedback Stabilization

Lyapunov-like characterizations for the concepts of nonuniform in time robust global asymptotic stability and input-to-state stability for time-varying systems are established. The main result of our work enables us to derive (1) necessary and sufficient conditions for feedback stabilization for affine in the control systems and (2) sufficient conditions for the propagation of the input-to-state stability property through integrators.
APOE and AGT in the Finnish p.Arg133Cys CADASIL population

CADASIL is an inherited systemic small vessel disease, the affected status of brain vessels leading to subcortical vascular dementia. The defective gene is NOTCH3 in which over 230 different pathogenic mutations have been identified. The clinical course of CADASIL is highly variable even within families. Previous studies have shown that additional genetic factors modify the phenotype.
Appetite Response among Those Susceptible or Resistant to Obesity

An alternative approach in determining cause, treatment, and prevention of obesity is to study those who appear resistant to the obesogenic environment. We examined appetite responses in 33 obesity resistant individuals (ORI) versus 28 obesity susceptible individuals (OSI). Fingerprick blood samples to measure ghrelin, total peptide YY (PYY), leptin, glucose, and insulin along with appetite ratings were collected at baseline and 15, 30, 60, 120, and 180 min following consumption of a standardized meal. Fasting, area under the curve (AUC), peak/nadir, and time to peak/nadir were compared. Participants completed the three factor eating questionnaire (TFEQ). No significant differences were observed for ghrelin or PYY. Higher leptin concentrations in the OSI disappeared after controlling for percent body fat (%BF). Significant differences in appetite ratings included a lower hunger nadir among OSI compared with ORI (P = 0.017). Dietary restraint (P < 0.001) and disinhibition (P < 0.001) were lower in ORI compared with OSI, with and without adjustment for %BF. Given the differential body weight of the study groups, similar observed ghrelin concentrations were unexpected, perhaps indicating OSI and ORI respond differently to the same ghrelin concentration. Also ORI response to hunger appears different as they exhibit lower levels of dietary restraint and disinhibition compared with OSI.
Insulin resistance in African-American and Caucasian women: differences in lipotoxicity, adipokines, and gene expression in adipose tissue and muscle.

OBJECTIVES We tested whether African-American (AA) women are different from Caucasian women in regard to lipotoxicity, adipokines, and gene expression in adipose tissue and muscle. DESIGN Insulin sensitivity (S(I)), plasma adipocytokine levels, intramyocellular lipid (IMCL), and the expression of candidate genes in adipose tissue and muscle were measured in AA and Caucasian women. SETTING This study was performed in an ambulatory general clinical research center. SUBJECTS Subjects were healthy, nondiabetic AA and Caucasian women. INTERVENTIONS There were no interventions. MAIN OUTCOME MEASURES Comparison of S(I), IMCL, plasma adiponectin, and the expression of candidate genes regulating adipogenesis, lipogenesis, and inflammation in adipose tissue and muscle. RESULTS AA had lower plasma adiponectin and IMCL when compared with Caucasian women with similar S(I). In sc adipose tissue (SAT), the expression of genes involved in adipogenesis including peroxisomal proliferator-activated receptor-gamma (PPARgamma) and lipin-1beta were also reduced in SAT of AA subjects (19%, P = 0.06, and 25%, P = 0.05, respectively). Similarly, 1-acylglycerol-3-phosphate acyltransferase 2 (AGPAT 2), stearoyl-coenzyme A desaturase-1 (SCD1), and CD36 mRNA expression was significantly reduced in SAT by 19, 54, and 28% respectively (P < 0.01 for all) in AA compared with Caucasian women. Yet the expression of CD68 in SAT was similar in both ethnic groups. Gene expression studies in muscle revealed a 31% reduction in expression of AGPAT 2 and a 72% reduction in SCD1 genes in AA. CONCLUSION AA women demonstrated lower expression of several PPARgamma-responsive genes in adipose tissue, lower plasma adiponectin, and decreased IMCL levels as compared with Caucasians, which suggests that African-Americans may be protected from lipotoxicity. Together these data suggest significant ethnic differences in the pathophysiology of insulin resistance.
International metal-on-metal multidisciplinary teams: do we manage patients with metal-on-metal hip arthroplasty in the same way? An analysis from the International Specialist Centre Collaboration on MOM Hips (ISCCoMH).

AIMS There are many guidelines that help direct the management of patients with metal-on-metal (MOM) hip arthroplasties. We have undertaken a study to compare the management of patients with MOM hip arthroplasties in different countries. METHODS Six international tertiary referral orthopaedic centres were invited to participate by organising a multi-disciplinary team (MDT) meeting, consisting of two or more revision hip arthroplasty surgeons and a musculoskeletal radiologist. A full clinical dataset including history, blood tests and imaging for ten patients was sent to each unit, for discussion and treatment planning. Differences in the interpretation of findings, management decisions and rationale for decisions were compared using quantitative and qualitative methods. RESULTS Overall agreement between the orthopaedic centres and the recommended treatment plans for the ten patients with MOM hip implants was moderate (kappa = 0.6). Full agreement was seen in a third of cases, however split decisions were also seen in a third of cases. Units differed in their interpretation of the significance of the investigation findings and put varying emphasis on serial changes, in the presence of symptoms. DISCUSSION In conclusion, the management of raised or rising blood metal ions, cystic pseudotumours and peri-acetabular osteolysis led to inconsistency in the agreement between centres. Coordinated international guidance and MDT panel discussions are recommended to improve consensus in decision making. TAKE HOME MESSAGE A lack of evidence and the subsequent variation in regulator guidance leads to differences in opinions, the clinical impact of which can be reduced through a multi-disciplinary team approach to managing patients with MOM hip implants. Cite this article: Bone Joint J 2016;98-B:179-86.
Dissecting the Luminosity Function of the Coma Cluster of Galaxies Using Canada-France-Hawaii Telescope Wide-Field Images

We determined the relative spatial density of the Coma Cluster galaxies, selected by luminosity and by central brightness, i.e., the luminosity function bivariate in central brightness. The Coma Cluster and control fields were imaged using the CFH12K (42′ × 28′) and UH8K (28′ × 28′) wide-field cameras at the Canada-France-Hawaii Telescope. Selected Hubble Space Telescope (HST) images were used for testing. Quantities were derived from measurements in at least two colors, which have the following features: (1) galaxies as faint as 3 times the luminosity of the brightest globular clusters are in the completeness region of our data. (2) We have a complete census (in the explored region) of low surface brightness galaxies with a central surface brightness almost as low as the faintest ones so far cataloged. (3) The explored area is among the largest ever sampled with CCDs at comparable depth for any cluster of galaxies. (4) The error budget includes all sources of errors known to date. Using HST images, we also discovered that blends of globular clusters, not resolved into individual components due to seeing, look like dwarf galaxies when observed from the ground and are numerous and bright. When mistaken as extended sources, they increase the steepness of the luminosity function at faint magnitudes. The derived Coma luminosity function is relatively steep (α = -1.4) over the 11 magnitudes sampled, but the slope and shape depend on color. A large population of faint low surface brightness galaxies was discovered, representing the largest contributor (in number) to the luminosity function at faint magnitudes. We found a clear progression for a faintening of the luminosity function from high surface brightness galaxies (μ ~ 20 mag arcsec-2) to galaxies of very faint central brightness (μ ~ 24.5 mag arcsec-2), and some evidence for a steepening. Compact galaxies, usually classified as stars and therefore not included in the luminosity function, are found to be a minor population in Coma.