Miracle-dz/UniFAR-FTUs huggingface dataset:
Hormone replacement therapy enhances IGF-1 signaling in skeletal muscle by diminishing miR-182 and miR-223 expressions: a study on postmenopausal monozygotic twin pairs

MiRNAs are fine‐tuning modifiers of skeletal muscle regulation, but knowledge of their hormonal control is lacking. We used a co‐twin case–control study design, that is, monozygotic postmenopausal twin pairs discordant for estrogen‐based hormone replacement therapy (HRT) to explore estrogen‐dependent skeletal muscle regulation via miRNAs. MiRNA profiles were determined from vastus lateralis muscle of nine healthy 54–62‐years‐old monozygotic female twin pairs discordant for HRT (median 7 years). MCF‐7 cells, human myoblast cultures and mouse muscle experiments were used to confirm estrogen's causal role on the expression of specific miRNAs, their target mRNAs and proteins and finally the activation of related signaling pathway. Of the 230 miRNAs expressed at detectable levels in muscle samples, qPCR confirmed significantly lower miR‐182, miR‐223 and miR‐142‐3p expressions in HRT using than in their nonusing co‐twins. Insulin/IGF‐1 signaling emerged one common pathway targeted by these miRNAs. IGF‐1R and FOXO3A mRNA and protein were more abundantly expressed in muscle samples of HRT users than nonusers. In vitro assays confirmed effective targeting of miR‐182 and miR‐223 on IGF‐1R and FOXO3A mRNA as well as a dose‐dependent miR‐182 and miR‐223 down‐regulations concomitantly with up‐regulation of FOXO3A and IGF‐1R expression. Novel finding is the postmenopausal HRT‐reduced miRs‐182, miR‐223 and miR‐142‐3p expression in female skeletal muscle. The observed miRNA‐mediated enhancement of the target genes' IGF‐1R and FOXO3A expression as well as the activation of insulin/IGF‐1 pathway signaling via phosphorylation of AKT and mTOR is an important mechanism for positive estrogen impact on skeletal muscle of postmenopausal women.
Individual Differences in Second Language Learning

This article is broadly concerned with the differences between individual language learners. In terms of particular content areas of Individual Differences (ID) research, it surveys developments in foreign language aptitude, motivation, learner strategies, and learner styles. A brief review of earlier research on aptitude is presented, followed by discussions of more contemporary work on the origin of aptitude, namely, as a residue of first language learning ability, and on the existence of evidence for “learner types. ” Motivation research is reviewed partly with regard to Robert Gardner's research, and then in terms of a wider framework for the functioning of motivation within an educational context. The review of learner strategies research emphasizes current attempts to develop taxonomies of such strategies, and to investigate their theoretical basis and their trainability. Finally, learner styles research, drawing on field independence theory, is discussed, and links are made with the research on aptitude. The article finishes with sections on conceptual and methodological issues in ID research.
Relação Entre Ritmo Circadiano, Turno e Rendimento Escolar de Alunos do Ensino Fundamental

Introduction. The cronotype or the preference that the hours of wak ing and sleeping and the daily activities can affect academics activities. Objective. To investigate the relationship of the circadian rhythm (biological clock), the starting time to school and school performance of adolescents from the city of Farroupilha/RS. Method. We applied Scale Circadian Rhythm-sleep/wake cycle for adolescents (Scale Morning/Evening - M/E) in the classroom for students from 6th to 9th grades of Elementary school. Results. The sample comprised 478 students from five public schools with a mean age of 12.52, 60% stu dents were morning and 40% were evening. The morning students that studied in the morning showed higher grades than the morning students that studied in the afternoon in four disciplines. The af ternoon students that studied in the morning showed higher grades in two of nine disciplines compared with those that studied in the afternoon. Conclusions. Students who study in the morning had a school performance that morning than the afternoon shift as well as the evening in both rounds.
The SH2 Domain-containing Inositol 5′-Phosphatase (SHIP) Recruits the p85 Subunit of Phosphoinositide 3-Kinase during FcγRIIb1-mediated Inhibition of B Cell Receptor Signaling*

Coligation of FcγRIIb1 with the B cell receptor (BCR) or FcεRI on mast cells inhibits B cell or mast cell activation. Activity of the inositol phosphatase SHIP is required for this negative signal. In vitro, SHIP catalyzes the conversion of the phosphoinositide 3-kinase (PI3K) product phosphatidylinositol 3,4,5-trisphosphate (PIP3) into phosphatidylinositol 3,4-bisphosphate. Recent data demonstrate that coligation of FcγRIIb1 with BCR inhibits PIP3-dependent Btk (Bruton’s tyrosine kinase) activation and the Btk-dependent generation of inositol trisphosphate that regulates sustained calcium influx. In this study, we provide evidence that coligation of FcγRIIb1 with BCR induces binding of PI3K to SHIP. This interaction is mediated by the binding of the SH2 domains of the p85 subunit of PI3K to a tyrosine-based motif in the C-terminal region of SHIP. Furthermore, the generation of phosphatidylinositol 3,4-bisphosphate was only partially reduced during coligation of BCR with FcγRIIb1 despite a drastic reduction in PIP3. In contrast to the complete inhibition of Tec kinase-dependent calcium signaling, activation of the serine/threonine kinase Akt was partially preserved during BCR and FcγRIIb1 coligation. The association of PI3K with SHIP may serve to activate PI3K and to regulate downstream events such as B cell activation-induced apoptosis.
Low-protein diet prevents tissue lipoprotein lipase activity increase in growing rats

The time course of changes in tissue lipolytic activities was studied in young rats during the consumption of a low-protein diet containing 50 g protein/kg (40 g wheat gluten +10 g casein/kg) for 28 d followed by balanced refeeding with 200 g protein/kg (160 g wheat gluten +40 g casein/kg) for 28 d. Lipoprotein lipase (LPL) activities were compared with the values of a control group fed a balanced diet containing 200 g protein/kg for 56 d. At the end of protein malnutrition period, the epididymal fat tissue LPL activity represented 36 %, and that of heart and gastrocnemius was 44 %, of those of the control group. These differences were accompanied by lower serum- and VLDL-triacylglycerols (TAG), respectively 47·6 % and 31 % of the control group values, probably resulting from reduced synthesis of VLDL-apolipoproteins (29 % of control group values), concomitant with liver lipid accumulation (4·8-fold) and little lipid storage in epididymal fat tissue. At day 2 of refeeding, there was no significant difference in liver and epididymal fat tissue LPL activities between experimental and control rats. At the end of the refeeding period, LPL activity of epididymal fat and liver lipolytic activity had increased and became similar to control group values. The consumption of a low-protein diet prevented the increase in extrahepatic LPL activities as observed in the control group. The alterations in LPL activity suggest that a low-protein diet limits lipid storage in adipose tissue due to reduced serum VLDL-TAG availability.
The effects of yoga-based and walking interventions on headaches, stress, and anxiety

ZHANNA DAVID. The effects of Yoga-based and walking interventions on headaches, stress, and anxiety. (Under the direction of Dr. SUSAN K. JOHNSON) This study examined whether interventions using yoga postures or yogic breathing (YB) can reduce headache frequency and severity, negative physiological and perceived effects of stress, depressive and anxiety symptoms relative to a physical activity (walking) comparison group as well as a wait list control. Participants with no prior yoga experience participated in a four week study that involved training and practice of yoga postures (N = 14), yogic breathing (N = 14), walking (N = 7) or being put on a wait-list (N = 15). Results indicate that while beneficial effects were observed in the three intervention groups, the yoga-based interventions demonstrated greater and consistent level of improvement on the following health measures: headache rate (frequency and severity of headaches), headache-associated difficulties measured by the Headache Disability Index (HDI), anxiety levels measured by the State Anxiety Inventory (SAI), and heart rate, although not all of them reached significance level. Practicing postures and YB for 20 minutes a day, up to 5 times a week for four weeks resulted in the significant drop in perceived anxiety, compared to either walking or control. Additional benefits for headache symptoms and overall physical and emotional health surfaced when only yoga-based interventions were compared to the control. There was a significant decrease in a headache rate for both postures and YB; a significant decrease in bodily
What Dreams May Come: Emotional Cascades and Nightmares in Borderline Personality Disorder

People diagnosed with borderline personality disorder (BPD) have been found to have a number of sleep problems, including frequent and distressing nightmares. The experience of nightmares is likely to worsen emotion dysregulation and decrease coping abilities the subsequent day, making it an important issue for clinicians to address. One recent theoretical model of BPD psychopathology, the Emotional Cascade Model (ECM), may shed light on this phenomenon by characterizing nightmares as the experience of emotional cascades that occur during sleep. A model is presented in which these cascades may carry over from a stressful day and lead to elevated cognitive activity during sleep, as well as nightmare-like phenomena. To test this model we used experience sampling from 47 participants exhibiting dysregulated behaviors—16 of them diagnosed with BPD. Negative emotion, rumination, and number of nightmares were assessed daily across two consecutive weeks. Analyses indicated that the BPD group experienced more frequent nightmares, that BPD diagnosis interacted with baseline trait rumination to prospectively predict number of nightmares reported during monitoring, and daily experience of emotional cascades predicted subsequent number of nightly nightmares. These findings held after controlling for key covariates, including sleep quality and diagnoses of depression and posttraumatic stress disorder. Important clinical interventions consistent with the ECM conceptualization of nightmares are proposed, including the potential for management of daily rumination and negative emotion, imagery rescripting for recurrent or anxiously anticipated nightmares, and potential prescription of prazosin (an alpha1-adrenergic antagonist) for the reduction of nightmares in this group.
A novel nuclear Src and p300 signaling axis controls migratory and invasive behavior in pancreatic cancer

The presence of Src in the nuclear compartment has been previously reported, although its significance has remained largely unknown. We sought to delineate the functions of the nuclear pool of Src within the context of malignant progression. Active Src is localized within the nuclei of human pancreatic cancer cells and mouse fibroblasts over-expressing c-Src where it is associated with p300. Nuclear Src additionally promotes the tyrosine phosphorylation of p300 in pancreatic cancer Panc-1 cells. Src, together with p300, is associated with the high-mobility group AT-hook (HMGA)2 and SET and MYND domain-containing protein (SMYD)3 gene promoters and regulates their expression in a Src-dependent manner. These nuclear Src-dependent events correlate with anchorage-independent soft-agar growth and the migratory properties in both pancreatic Panc-1 cells and mouse fibroblasts over-expressing Src. Moreover, analyses of human pancreatic ductal adenocarcinoma (PDAC) tumor tissues detected the association of nuclear Src with the HMGA2 and SMYD3 gene promoters. Our findings for the first time show the critical importance of nuclear Src and p300 function in the migratory properties of pancreatic cancer cells. Further, data together identify a previously unknown role of nuclear Src in the regulation of gene expression in association with p300 within the context of cells harboring activated or over-expressing Src. This novel mechanism of nuclear Src-p300 axis in PDAC invasiveness and metastasis may provide an opportunity for developing more effective early clinical interventions for this lethal disease. Active Src is complexed with and phosphorylates p300 in the nucleus, and the complex is bound to HMGA2 and SMYD3 genes, thereby regulating their expression to promote pancreatic tumor cell migration and invasiveness.
UV-Optical Colors as Probes of Early-Type Galaxy Evolution

We have studied ~2100 early-type galaxies in the SDSS DR3 which have been detected by the GALEX Medium Imaging Survey (MIS), in the redshift range 0 < z < 0.11. Combining GALEX UV photometry with corollary optical data from the SDSS, we find that, at a 95% confidence level, at least ~30% of galaxies in this sample have UV to optical colors consistent with some recent star formation within the last Gyr. In particular, galaxies with an NUV − r color less than 5.5 are very likely to have experienced such recent star formation, taking into account the possibility of a contribution to NUV flux from the UV upturn phenomenon. We find quantitative agreement between the observations and the predictions of a semianalytical ΛCDM hierarchical merger model and deduce that early-type galaxies in the redshift range 0 < z < 0.11 have ~1%-3% of their stellar mass in stars less than 1 Gyr old. The average age of this recently formed population is ~300-500 Myr. We also find that “monolithically” evolving galaxies, where recent star formation can be driven solely by recycled gas from stellar mass loss, cannot exhibit the blue colors (NUV − r < 5.5) seen in a significant fraction (~30%) of our observed sample.
Insulin-like growth factor-I and insulin are associated with the presence and advancement of adenomatous polyps.

BACKGROUND & AIMS Insulin and insulin-like growth factor-I (IGF-I) affect proliferation, differentiation, and apoptosis and are potential risk factors for colorectal cancer (CRC). Visceral obesity, possibly via hyperinsulinemia, has also been linked to CRC risk. We evaluated the relationship of insulin, IGF-I, insulin-like growth factor binding protein (IGFBP) 3, and visceral adipose tissue (VAT) in subjects with adenomatous polyps, the precursor lesion of colorectal cancer. METHODS Participants were asymptomatic subjects who underwent screening flexible sigmoidoscopy (FSG) within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Subjects underwent single-slice, computerized tomography scanning to measure VAT and serum fasting insulin, IGF-I, and IGFBP-3 measurements. RESULTS Four hundred fifty-eight subjects were enrolled, of which 202 subjects had an adenoma, 70 of which were an advanced adenoma. IGF-I (P = .02), IGF-I/IGFBP-3 ratio (P = .003), and insulin (P = .02) were significantly increased in subjects with adenomas compared with controls. In an unadjusted logistic regression analysis using sex-specific quartile cut points, subjects in quartile 4 in comparison with quartile 1 of IGF-I (odds ratio [OR] = 1.7; [95% CI: 1.0-2.9], Ptrend = .03), IGF-I/IGFBP-3 ratio (OR = 1.9 [95% CI: 1.1-3.3], Ptrend = .01), and insulin (OR = 2.1 [95% CI: 1.2-3.6], Ptrend = .04) were at increased risk of adenoma. When limiting the case group to advanced adenomas, the effect was more pronounced: IGF-I (OR = 2.8 [95% CI: 1.3-6.2], Ptrend = .006), IGF-I/IGFBP-3 ratio (OR = 2.3, [95% CI: 1.0-5.2], Ptrend = .04), and insulin (OR = 2.3 [95% CI: 1.1-4.9], Ptrend = .14). Visceral adipose tissue was not associated with adenoma risk. CONCLUSIONS Levels of IGF-I, ratio of IGF-I/IGFBP-3, and insulin are associated with adenomas and even more so with advanced adenomas. These data support the hypothesis that insulin and IGF-I may contribute to the development and advancement of adenomatous polyps.
Non-linear feature extraction by linear PCA using local kernel

This paper presents how to extract non-linear features by linear PCA. KPCA is effective but the computational cost is the drawback. To realize both non-linearity and low computational cost simultaneously, the idea of local kernel is used. The mapped features of the polynomial kernel can be described explicitly. When input features are divided into some local features and the polynomial kernel is applied to each local features independently, the dimension of mapped features does not become so high. In addition, the inner product with all local mapped features corresponds to the local summation kernel. Thus, KPCA with the local summation kernel can be solved by linear PCA. The proposed approach is evaluated in object categorization problem which requires high non-linearity and computational cost. The proposed method gives much higher accuracy than linear PCA. The computational cost is lower than KPCA though the accuracy is slightly worse than KPCA.
Maduramicin Rapidly Eliminates Malaria Parasites and Potentiates the Gametocytocidal Activity of the Pyrazoleamide PA21A050

ABSTRACT New strategies targeting Plasmodium falciparum gametocytes, the sexual-stage parasites that are responsible for malaria transmission, are needed to eradicate this disease. Most commonly used antimalarials are ineffective against P. falciparum gametocytes, allowing patients to continue to be infectious for over a week after asexual parasite clearance. A recent screen for gametocytocidal compounds demonstrated that the carboxylic polyether ionophore maduramicin is active at low nanomolar concentrations against P. falciparum sexual stages. In this study, we showed that maduramicin has an EC50 (effective concentration that inhibits the signal by 50%) of 14.8 nM against late-stage gametocytes and significantly blocks in vivo transmission in a mouse model of malaria transmission. In contrast to other reported gametocytocidal agents, maduramicin acts rapidly in vitro, eliminating gametocytes and asexual schizonts in less than 12 h without affecting uninfected red blood cells (RBCs). Ring stage parasites are cleared by 24 h. Within an hour of drug treatment, 40% of the normally crescent-shaped gametocytes round up and become spherical. The number of round gametocytes increases to >60% by 2 h, even before a change in membrane potential as monitored by MitoProbe DiIC1 (5) is detectable. Maduramicin is not preferentially taken up by gametocyte-infected RBCs compared to uninfected RBCs, suggesting that gametocytes are more sensitive to alterations in cation concentration than RBCs. Moreover, the addition of 15.6 nM maduramicin enhanced the gametocytocidal activity of the pyrazoleamide PA21A050, which is a promising new antimalarial candidate associated with an increase in intracellular Na+ concentration that is proposed to be due to inhibition of PfATP4, a putative Na+ pump. These results underscore the importance of cation homeostasis in sexual as well as asexual intraerythrocytic-stage P. falciparum parasites and the potential of targeting this pathway for drug development.
Cytochrome P450 and Glutathione S-Transferase mRNA Expression in Human Fetal Liver Hematopoietic Stem Cells

During fetal development, the liver serves as the primary hematopoietic organ in which hematopoietic stem cells (HSC) capable of initiating long-term hematopoiesis comprise a large proportion of the hepatic cell population. Although HSC are potential targets for transplacental chemicals, little is known regarding their xenobiotic biotransformation ability. We quantitated the steady-state mRNA expression of six cytochrome P450 (P450) and 11 glutathione S-transferase (GST) isoforms in CD34+-selected HSC isolated from second trimester human fetal liver donors, genotyped donors for polymorphic hGSTM1 and hGSTT1 status, and analyzed gene expression in HSC relative to total liver from donors of similar gestational ages. Several P450 isoforms, including CYP1A1, CYP2E1, CYP3A4, and CYP3A5, were expressed at low levels in HSC (relative mRNA expression CYP3A5 > CYP1A1 > CYP2E1 > CYP3A4). CYP1A2 and CYP3A7 were not detected in HSC. The CYP3A4/5 mRNA expression in HSC was accompanied by detectable CYP3A protein and low midazolam oxidation activity. Several GST isoforms, including hGSTM1, hGSTM2, hGSTM4, and hGSTP1, were significantly higher in HSC as compared with total fetal liver. With the exception of hGSTA4, alpha class GST were not detected in HSC. GST expression in HSC was accompanied by substantial GST catalytic activity toward 1-chloro-2,4-dinitrobenzene. In summary, our data indicate that fetal liver CD34+-derived HSC constitutively express several P450 isoforms at low levels relative to total hepatic cell populations but have a higher capacity for GST conjugation reactions through mu and pi class isoforms. The functional ramifications of these observations are discussed relative to the sensitivity of human fetal HSC to transplacental chemical injury.
On longest paths and diameter in random apollonian networks

We consider the following iterative construction of a random planar triangulation. Start with a triangle embedded in the plane. In each step, choose a bounded face uniformly at random, add a vertex inside that face and join it to the vertices of the face. After n – 3 steps, we obtain a random triangulated plane graph with n vertices, which is called a Random Apollonian Network (RAN). We show that asymptotically almost surely (a.a.s.) a longest path in a RAN has length o(n), refuting a conjecture of Frieze and Tsourakakis. We also show that a RAN always has a cycle (and thus a path) of length ( 2 n − 5 ) log ⁡ 2 / log ⁡ 3 , and that the expected length of its longest cycles (and paths) is Ω ( n 0.88 ) . Finally, we prove that a.a. s. the diameter of a RAN is asymptotic to c log ⁡ n , where c ≈ 1.668 is the solution of an explicit equation. © 2014 Wiley Periodicals, Inc. Random Struct. Alg. , 45, 703–725, 2014
Perinatal outcomes based on the institute of medicine guidelines for weight gain in twin pregnancies

Abstract Objective: To estimate the impact of the Institute of Medicine’s (IOM) weight gain recommendations on perinatal outcomes in twin pregnancies. Methods: In this multicenter cohort study, using the 2009 IOM guidelines, we examined pregnancy outcomes in 570 uncomplicated diamniotic twin pregnancies. Subjects were grouped according to pre-pregnancy body mass index. Perinatal outcomes were assessed based on whether maternal weekly weight gain was less than, at, or in excess of the recommended IOM guidelines. Results: In women with a normal pre-pregnancy BMI, patients whose weight gain met the IOM recommendations had a significantly higher mean gestational age at delivery; less prematurity and larger birth weight infants compared to women whose weekly weight gain was less or excess than the recommended IOM guidelines. Similarly, when compared with their low weight gain counterparts, overweight women with appropriate weight gain had improved outcomes including higher mean gestational age at delivery, higher birth weight infants and less prematurity. In obese women, the amount of pregnancy weight gain did not impact perinatal outcomes. Conclusion: Our results confirm that weekly maternal weight gain according to the IOM guidelines results in improved outcomes in twin pregnancies. Importantly, women with a normal or overweight pre-pregnancy BMI whose weekly weight gain was less than recommended, had increased risks of prematurity and lower birth weight infants. Similarly, women with a normal pre-pregnancy BMI whose weekly weight gain was excess than recommended had increased risks of prematurity and lower birth weight infants.