Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of adipocytokines in insulin resistance in normal pregnancy: visfatin concentrations in early pregnancy predict insulin sensitivity.

BACKGROUND Throughout pregnancy maternal adipose tissue is metabolically active, producing adipocytokines involved in the process of insulin resistance. We explored the role of serum adipocytokines, including the newly identified adipocytokine visfatin, in the process of insulin resistance in normal pregnancy. METHODS We examined 80 pregnant nonobese, nondiabetic white women during the 3 trimesters of pregnancy. All study participants underwent anthropometric measurements, adipocytokine evaluation, and a 75-g oral glucose tolerance test. Homeostasis mathematical model assessment (HOMA-R), insulin sensitivity index (ISI), and indices of beta-cell secretion were calculated. RESULTS Maternal weight, percentage total body fat, hip circumference, and indices of beta-cell secretion increased significantly during the 3 trimesters, and HOMA-R and ISI increased and decreased, respectively, in the 3rd trimester. During early pregnancy, insulin resistance, beta-cell secretion, and weight correlated positively with leptin. During the 1st trimester, visfatin correlated negatively with percentage body fat and was the best positive predictor of 2nd trimester ISI. In the 2nd trimester, serum visfatin was the best negative predictor of percentage body fat. CONCLUSIONS During normal pregnancy of nonobese, nondiabetic women, adipose tissue increases, accompanied by a significant progressive increase of insulin resistance. Visfatin concentrations in the 1st trimester positively predict insulin sensitivity during the 2nd trimester. Body fat mass during 1st trimester of pregnancy is negatively associated with insulin sensitivity during the 2nd trimester and perhaps should be kept under control.
Alcohol-Related Dysfunction in Working-Age Men in Izhevsk, Russia: An Application of Structural Equation Models to Study the Association with Education

Background Acute alcohol-related dysfunctional behaviours, such as hangover, are predictive of poor health and mortality. Although much is known about the association of education with alcohol consumption, little is known about its association with these dysfunctional behaviours. Methods The study population was 1,705 male drinkers aged 25–54 years resident in the city of Izhevsk, Russia who participated in a cross-sectional survey (2003–6). Structural equation modelling was used to examine the relationships between education, beverage and non-beverage alcohol intake, drinking patterns, and acute alcohol-related dysfunction score among these drinkers. Results Dysfunction was related to all other drinking variables, with the strongest predictors being spirit intake, non-beverage alcohol consumption and drinking patterns. There was a strong relationship between education and acute dysfunction which was not explained by adjusting for alcohol intake and drinking patterns (mean adjusted dysfunction score 0.35 SD (95% CI 0.10, 0.61) lower in men with higher versus secondary education). Conclusions Although by definition one or more aspects of alcohol consumption should explain the educational differences in alcohol-related dysfunction, detailed information on drinking only partly accounted for the observed patterns. Thus beyond their intrinsic interest, these results illustrate the challenges in constructing statistical models that convincingly identify the pathways that link educational differences to health-related outcomes.
Intermittent Parathyroid Hormone After Prolonged Alendronate Treatment Induces Substantial New Bone Formation and Increases Bone Tissue Heterogeneity in Ovariectomized Rats

Postmenopausal osteoporosis is often treated with bisphosphonates (eg, alendronate, [ALN]), but oversuppression of bone turnover by long‐term bisphosphonate treatment may decrease bone tissue heterogeneity. Thus, alternate treatment strategies after long‐term bisphosphonates are of great clinical interest. The objective of the current study was to determine the effect of intermittent parathyroid hormone (PTH) following 12 weeks of ALN (a bisphosphonate) treatment in 6‐month‐old, ovariectomized (OVX) rats on bone microarchitecture, bone remodeling dynamics, and bone mechanical properties at multiple length scales. By using in vivo μCT and 3D in vivo dynamic bone histomorphometry techniques, we demonstrated the efficacy of PTH following ALN therapy for stimulating new bone formation, and increasing trabecular thickness and bone volume fraction. In healthy bone, resorption and formation are coupled and balanced to sustain bone mass. OVX results in resorption outpacing formation, and subsequent bone loss and reduction in bone tissue modulus and tissue heterogeneity. We showed that ALN treatment effectively reduced bone resorption activity and regained the balance with bone formation, preventing additional bone loss. However, ALN treatment also resulted in significant reductions in the heterogeneity of bone tissue mineral density and tissue modulus. On the other hand, PTH treatment was able to shift the bone remodeling balance in favor of formation, with or without a prior treatment with ALN. Moreover, by altering the tissue mineralization, PTH alleviated the reduction in heterogeneity of tissue material properties induced by prolonged ALN treatment. Furthermore, switching to PTH treatment from ALN improved bone's postyield mechanical properties at both the whole bone and apparent level compared to ALN alone. The current findings suggest that intermittent PTH treatment should be considered as a viable treatment option for patients with prior treatment with bisphosphonates. © 2017 American Society for Bone and Mineral Research.
Poly(ADP-ribose) Polymerase-1-mediated Cell Death in Astrocytes Requires NAD+ Depletion and Mitochondrial Permeability Transition*

Extensive activation of poly(ADP-ribose) polymerase-1 (PARP-1) by DNA damage is a major cause of caspase-independent cell death in ischemia and inflammation. Here we show that NAD+ depletion and mitochondrial permeability transition (MPT) are sequential and necessary steps in PARP-1-mediated cell death. Cultured mouse astrocytes were treated with the cytotoxic concentrations of N-methyl-N′-nitro-N-nitrosoguanidine or 3-morpholinosydnonimine to induce DNA damage and PARP-1 activation. The resulting cell death was preceded by NAD+ depletion, mitochondrial membrane depolarization, and MPT. Sub-micromolar concentrations of cyclosporin A blocked MPT and cell death, suggesting that MPT is a necessary step linking PARP-1 activation to cell death. In astrocytes, extracellular NAD+ can raise intracellular NAD+ concentrations. To determine whether NAD+ depletion is necessary for PARP-1-induced MPT, NAD+ was restored to near-normal levels after PARP-1 activation. Restoration of NAD+ enabled the recovery of mitochondrial membrane potential and blocked both MPT and cell death. Furthermore, both cyclosporin A and NAD+ blocked translocation of the apoptosis-inducing factor from mitochondria to nuclei, a step previously shown necessary for PARP-1-induced cell death. These results suggest that NAD+ depletion and MPT are necessary intermediary steps linking PARP-1 activation to AIF translocation and cell death.
A pilot program at the worksite to reduce adverse self-medication behaviors

A Next Generation Personal Education Program (PEP-NG) that captures self-reported medication behaviors and delivers a tailored educational intervention on a touchscreen interface was piloted with 11 adults with hypertension, aged 45–60 years, in a worksite setting. A time series design with multiple institution of treatment (four visits over three months) was employed. Blood pressure (BP), self-medication behaviors, self-efficacy, and knowledge for avoiding adverse self-medication behaviors were assessed at each of four visits. Satisfaction was assessed once at visit 4. Measures pre-PEP (visit 1) to visit 4 were compared with paired t-tests. The adverse self-medication behavior risk score decreased significantly from visit 1 to visit 4 (p < 0.05) with a medium effect size. Both knowledge and self-efficacy for avoiding adverse self-medication behaviors increased significantly (p < 0.05) with large effect sizes. All six participants not at BP goal (<140/90 mmHg) on visit 1 were at goal by visit 4. User satisfaction was high as assessed by both quantitative measures and qualitative interviews. These positive results suggest the PEP could play a central role in worksite wellness programs aimed at workers with hypertension.
Herpes labialis among dental healthcare providers in Nigeria

Introduction: The epidemiology of herpes labialis has been relatively neglected. The objective of this study was to determine the prevalence and risk factors of self-reported herpes labialis among Nigerian dental health providers. Materials and Methods: This cross-sectional study of final year dental students and dentists undergoing postgraduate training at University of Benin Teaching Hospital, Benin City, Nigeria was conducted in June, 2014. The demographic information, lifetime and period (previous year) experience of the herpes labialis, perceived triggers and action taken during the last episode were obtained using a self-administered questionnaire. Results: The annual prevalence of herpes labialis was 7.4% while the lifetime prevalence was 22.1%. The lifetime prevalence was significantly associated with marital status, professional status and family history of herpes labialis. However, in binary regression, it was only marital status and family history of herpes labialis that emerged as the determinants of this lifetime prevalence. The most common trigger factors reported by the participants for the last episode of herpes labialis were fever, malaria, fatigue and stress. The actions taken by participants for the last episode of herpes labialis were using drugs without prescription (14.3%), application of lubricant (23.8%), nothing (57.1%) and could not remember (4.8%). Conclusion: Data from this study revealed that one out of fourteen and one out of five every studied dental healthcare providers had experienced herpes labialis in the last 12 months and their lifetime respectively. The reduction of fever inducing infections, stress and fatigue which were major triggers will help decrease herpes labialis among this studied group.
Human macrophages induced in vitroby macrophage colony‐stimulating factor are deficient in IL‐12 production

IL‐12 is important for Th1 differentiation. Myeloid‐derived antigen‐presenting cells (APC) such as monocytes, macrophages (Mϕ) and dendritic cells (DC) are believed to be major sources of IL‐12 in vivo. We have compared IL‐12 production of fresh monocytes with Mϕ differentiated in vitro using macrophage colony‐stimulating factor (M‐CSF) or human plasma, and in vitro generated dendritic cells, since these differentiated cell types represent APC at sites of antigen challenge. Macrophages stimulated with lipopolysaccharide (LPS) or heat‐killed Listeria monocytogenes in the presence or absence of IFN‐γ produced minimal IL‐12 p70 by comparison with DC or monocytes, despite comparable production of TNF‐α. M‐CSF‐induced Mϕ produced low levels of IL‐10 constitutively and high levels after stimulation with LPS, but neutralization of IL‐10 did not augment Mϕ IL‐12 production. Exposure of Mϕ to TNF‐α, granulocyte‐macrophage CSF or IFN‐γ did not substantially up‐regulate IL‐12. Therefore M‐CSF induces a differentiated Mϕ phenotype in which IL‐12 production is down‐regulated, perhaps irreversibly. This may be the default pathway for monocyte‐Mϕ development in the absence of inflammation.
Impaired Angiogenesis, Delayed Wound Healing and Retarded Tumor Growth in Perlecan Heparan Sulfate-Deficient Mice

Perlecan, a modular proteoglycan carrying primary heparan sulfate (HS) side chains, is a major component of blood vessel basement membranes. It sequesters growth factors such as fibroblast growth factor 2 (FGF-2) and regulates the ligand-receptor interactions on the cell surface, and thus it has been implicated in the control of angiogenesis. Both stimulatory and inhibitory effects of perlecan on FGF-2 signaling have been reported. To understand the in vivo function of HS carried by perlecan, the perlecan gene heparan sulfate proteoglycan 2 (Hspg2) was mutated in mouse by gene targeting. The HS at the NH2 terminus of perlecan was removed while the core protein remained intact. Perlecan HS-deficient (Hspg2Δ3/Δ3) mice survived embryonic development and were apparently healthy as adults. However, mutant mice exhibited significantly delayed wound healing, retarded FGF-2-induced tumor growth, and defective angiogenesis. In the mouse corneal angiogenesis model, FGF-2-induced neovascularization was significantly impaired in Hspg2Δ3/Δ3 mutant mice. Our results suggest that HS in perlecan positively regulates the angiogenesis in vivo.
Domination theory and the crapo β-invariant

Relations are established between the domination and minimum domination invariants and a matroid invariant known as the Crapo β-invariant. Using these results, it is possible to extend well-known results of domination theory. Moreover, the proofs of these results are considerably simplified. Matroid theory is made available to reliability applications by introducing a certain regularity assumption.
Ribonucleotide Reductase Association with Mammalian Liver Mitochondria*

Background: Mitochondrial DNA replication is supplied by precursor pools distinct from pools supplying nuclear DNA replication. Results: Liver mitochondrial extracts contain significant ribonucleotide reductase activity, associated with nucleoids. Conclusion: Intramitochondrial ribonucleotide reduction may be a significant source of mitochondrial dNTPs. Significance: Knowing sources of mitochondrial dNTP pools may lead toward understanding mitochondrial genomic stability. Deoxyribonucleoside triphosphate pools in mammalian mitochondria are highly asymmetric, and this asymmetry probably contributes to the elevated mutation rate for the mitochondrial genome as compared with the nuclear genome. To understand this asymmetry, we must identify pathways for synthesis and accumulation of dNTPs within mitochondria. We have identified ribonucleotide reductase activity specifically associated with mammalian tissue mitochondria. Examination of immunoprecipitated proteins by mass spectrometry revealed R1, the large ribonucleotide reductase subunit, in purified mitochondria. Significant enzymatic and immunological activity was seen in rat liver mitochondrial nucleoids, isolated as described by Wang and Bogenhagen (Wang, Y., and Bogenhagen, D. F. (2006) J. Biol. Chem. 281, 25791–25802). Moreover, incubation of respiring rat liver mitochondria with [14C]cytidine diphosphate leads to accumulation of radiolabeled deoxycytidine and thymidine nucleotides within the mitochondria. Comparable results were seen with [14C]guanosine diphosphate. Ribonucleotide reduction within the mitochondrion, as well as outside the organelle, needs to be considered as a possibly significant contributor to mitochondrial dNTP pools.
Effect of different doses of aerobic exercise training on total bilirubin levels.

UNLABELLED Low serum bilirubin levels have been associated with increased risk for cardiovascular disease, and recent data suggest that lower body fat and reductions in weight are associated with higher bilirubin levels. However, it is unknown if exercise training can increase bilirubin levels and whether a higher dose of exercise will further increase bilirubin levels compared with a lower dose. PURPOSE The primary aim of our current report was to examine whether exercise dose affects bilirubin levels in obese postmenopausal women from the Dose-Response to Exercise in Women trial. In addition, we evaluated whether changes in fitness, insulin sensitivity, and waist circumference associated with exercise training were associated with change in bilirubin levels. METHODS Participants (n = 419) were randomized to the control group or to 4, 8, and 12 kcal·kg⁻¹·wk⁻¹ (KKW) of exercise training at an intensity of 50% of aerobic capacity. Total bilirubin levels were evaluated at baseline and at follow-up. RESULTS Exercise training significantly increased serum bilirubin levels only in the 12-KKW group (0.044 mg·dL⁻¹, P = 0.026) compared with the control group (0.004 mg·dL⁻¹). Subgroup analyses showed that there was a significant increase in bilirubin levels in participants in the 12-KKW group (0.076 mg·dL⁻¹) who were classified as insulin resistant (homeostatic model assessment for insulin resistance score > 2.6) compared with insulin-resistant control participants (0.018 mg·dL⁻¹, P = 0.028). CONCLUSIONS Our findings suggest that high doses of exercise training are necessary to significantly increase bilirubin levels in previously sedentary postmenopausal women and especially those with impaired glucose metabolism.
A size contrast illusion without physical size differences.

One of the size-contrast illusions best known is the Ebbinghaus figure (frequently referred to as Titchner's circles). In this figure a circle surrounded by small circles is seen as larger than a circle surrounded by large circles. Although frequently reproduced in elementary texts, very little work has actually been done on this configuration, and an adequate explanation of its effect is still lacking. Ohwaki (1960), Springbett (1961), Day (1961), and Schiller and Wiener (1962) have shown, however, that the illusion is probably not of retinal origin, since the test and inducing elements can be placed into different eyes and the illusion still seen in the fused image. Further evidence that central processes may be involved is found in the demonstration shown in Figure 1. When stereoscopically fused the top configuration appears as a central disc with four surrounding circles imaged some distance behind the plane of the central test circle; the lower configuration has the central disc at the same stereoscopic distance as the test disc in the first group, but the surrounding circles are seen as considerably closer. By the operation of size constancy the surrounding circles that are apparently closer appear smaller than the surrounding circles that are apparently farther away, although all of the circles in the figure are physically the same size. The relevant question has to do with the apparent size of the central circles in Figure 1, those circles which are stereoscopically at the same distance. Twelve observers were used, all with normal or corrected visual acuity of 20/25 or better and with normal stereopsis as measured on a Keystone telebinocular. They viewed the figures through a lens stereoscope and were asked to judge the relative size of the central discs in a forced-choice paradigm. After the first judgment, the left and right views were interchanged so as to reverse the disparities and the
Decentralized Control of Large-Scale Uncertain Nonlinear Systems by Linear Output Feedback

This paper studies the problem of global decentralized control by output feedback for large-scale uncertain systems whose subsystems are interconnected not only by their outputs but also by their unmeasurable states. We show that under a linear growth condition, there is a decentralized output feedback controller rendering the closed-loop system globally exponentially stable. This is accomplished by extending an output feedback domination design that requires only limited infor- mation about the nonlinear system. We will apply our design to lower, upper, and non-triangular nonlinear systems. The significance of our results is that we do not need to have prior information about the nonlinearities of the system. Furthermore, we need to only employ a linear observer in combination with a linear controller to stabilize the system. A time-varying output feedback con- troller is also constructed for use with large-scale systems that have unknown parameters. 1. Introduction. Decentralized control of interconnected systems has been an area of considerable research due to its obvious practical application to current prob- lems in the field of controls. Large-scale systems have very complex dynamic models due to the uncertain environment, the varying system parameters, and the intercon- nected structure of the system. Also it is inevitable that nonlinearities are prevalent throughout the dynamics of the interconnected systems. All these issues make the stabilization of such large-scale systems a difficult control problem. Though quite challenging, the research of large-scale systems are relevant to such areas as commu- nication networks, satellite constellations, and the formation control of autonomous vehicles. The research of large-scale nonlinear systems began in the late 1960's and early 1970's. One of the earliest investigations into the nonlinear issues of large-scale sys- tems centered around time-varying stabilization (2). The early research in (7) demon- strated a method of using high-gain state feedback to stabilize the nonlinearities of the large-scale systems. The research in the early 1980's focused on the use of state feedback to globally stabilize large-scale nonlinear systems. Adaptive control was ap- plied in (3) to stabilize a class of large-scale nonlinear systems with success. Output feedback had also been applied to linear large-scale system in such papers as (1), (15),
Mutations in the Caenorhabditis elegans U2AF Large Subunit UAF-1 Alter the Choice of a 3′ Splice Site In Vivo

The removal of introns from eukaryotic RNA transcripts requires the activities of five multi-component ribonucleoprotein complexes and numerous associated proteins. The lack of mutations affecting splicing factors essential for animal survival has limited the study of the in vivo regulation of splicing. From a screen for suppressors of the Caenorhabditis elegans unc-93(e1500) rubberband Unc phenotype, we identified mutations in genes that encode the C. elegans orthologs of two splicing factors, the U2AF large subunit (UAF-1) and SF1/BBP (SFA-1). The uaf-1(n4588) mutation resulted in temperature-sensitive lethality and caused the unc-93 RNA transcript to be spliced using a cryptic 3′ splice site generated by the unc-93(e1500) missense mutation. The sfa-1(n4562) mutation did not cause the utilization of this cryptic 3′ splice site. We isolated four uaf-1(n4588) intragenic suppressors that restored the viability of uaf-1 mutants at 25°C. These suppressors differentially affected the recognition of the cryptic 3′ splice site and implicated a small region of UAF-1 between the U2AF small subunit-interaction domain and the first RNA recognition motif in affecting the choice of 3′ splice site. We constructed a reporter for unc-93 splicing and using site-directed mutagenesis found that the position of the cryptic splice site affects its recognition. We also identified nucleotides of the endogenous 3′ splice site important for recognition by wild-type UAF-1. Our genetic and molecular analyses suggested that the phenotypic suppression of the unc-93(e1500) Unc phenotype by uaf-1(n4588) and sfa-1(n4562) was likely caused by altered splicing of an unknown gene. Our observations provide in vivo evidence that UAF-1 can act in regulating 3′ splice-site choice and establish a system that can be used to investigate the in vivo regulation of RNA splicing in C. elegans.