Miracle-dz/UniFAR-FTUs huggingface dataset:
Insulin Suppresses Atrophy- and Autophagy-related Genes in Heart Tissue and Cardiomyocytes Through AKT/FOXO Signaling

Abstract Insulin is an important regulator of the ubiquitin-proteasome system (UPS) and of lysosomal proteolysis in cardiac muscle. However, the role of insulin in the regulation of the muscle atrophy-related Ub-ligases atrogin-1 and MuRF1 as well as in autophagy, a major adaptive response to nutritional stress, in the heart has not been characterized. We report here that acute insulin deficiency in the cardiac muscle of rats induced by streptozotocin increased the expression of atrogin-1 and MuRF1 as well as LC3 and Gabarapl1, 2 autophagy-related genes. These effects were associated with decreased phosphorylation levels of Akt and its downstream target Foxo3a; this phenomenon is a well-known effect that permits the maintenance of Foxo in the nucleus to activate protein degradation by proteasomal and autophagic processes. The administration of insulin increased Akt and Foxo3a phosphorylation and suppressed the diabetes-induced expression of Ub-ligases and autophagy-related genes. In cultured neonatal rat cardiomyocytes, nutritional stress induced by serum/glucose deprivation strongly increased the expression of Ub-ligases and autophagy-related genes; this effect was inhibited by insulin. Furthermore, the addition of insulin in vitro prevented the decrease in Akt/Foxo signaling induced by nutritional stress. These findings demonstrate that insulin suppresses atrophy- and autophagy-related genes in heart tissue and cardiomyocytes, most likely through the phosphorylation of Akt and the inactivation of Foxo3a.
Increased prevalence and mortality in undiagnosed celiac disease.

BACKGROUND & AIMS The historical prevalence and long-term outcome of undiagnosed celiac disease (CD) are unknown. We investigated the long-term outcome of undiagnosed CD and whether the prevalence of undiagnosed CD has changed during the past 50 years. METHODS This study included 9133 healthy young adults at Warren Air Force Base (sera were collected between 1948 and 1954) and 12,768 gender-matched subjects from 2 recent cohorts from Olmsted County, Minnesota, with either similar years of birth (n = 5558) or age at sampling (n = 7210) to that of the Air Force cohort. Sera were tested for tissue transglutaminase and, if abnormal, for endomysial antibodies. Survival was measured during a follow-up period of 45 years in the Air Force cohort. The prevalence of undiagnosed CD between the Air Force cohort and recent cohorts was compared. RESULTS Of 9133 persons from the Air Force cohort, 14 (0.2%) had undiagnosed CD. In this cohort, during 45 years of follow-up, all-cause mortality was greater in persons with undiagnosed CD than among those who were seronegative (hazard ratio = 3.9; 95% confidence interval, 2.0-7.5; P < .001). Undiagnosed CD was found in 68 (0.9%) persons with similar age at sampling and 46 (0.8%) persons with similar years of birth. The rate of undiagnosed CD was 4.5-fold and 4-fold greater in the recent cohorts, respectively, than in the Air Force cohort (both P < or = .0001). CONCLUSIONS During 45 years of follow-up, undiagnosed CD was associated with a nearly 4-fold increased risk of death. The prevalence of undiagnosed CD seems to have increased dramatically in the United States during the past 50 years.
Potential protective effect of long-term therapy with Xuezhikang on left ventricular diastolic function in patients with essential hypertension.

OBJECTIVE To investigate the benefits of long-term therapy with Xuezhikang, a cholestin extract, in combination with calcium channel blockers for improvement of left ventricular (LV) hypertrophy and function in patients with essential hypertension, as determined using echocardiography. DESIGN Fifty-five (55) hypertensive patients with normal blood low-density lipoprotein cholesterol (LDL-C) levels were randomly assigned to the Xuezhikang group (n = 28, 1200 mg/d of Xuezhikang) or the placebo group (n = 27, matched placebo). All of the patients were treated with extended-release nifedipine (20 mg twice daily). Thirty (30) normotensive subjects, matched for age and gender, were selected as a control group. Conventional echocardiography and tissue Doppler imaging were used to measure the left ventricle (LV) wall thickness and LV diastolic function at weeks 0, 24, and 72 during the period of observation. The serum levels of lipids, carboxy-terminal propeptide of procollagen type I (PIP), and C-reactive protein (CRP) were determined as well. RESULTS The hypertensive patients had significantly elevated PIP and CRP levels in serum, increased LV wall thickness, and impaired LV diastolic function compared with the normotensive subjects (0.01 < p < 0.05). Compared with the placebo group, the transmitral flow velocities (E/A ratio) (1.11 +/- 0.36 versus 0.85 +/- 0.24, p < 0.01) and the myocardial motion velocities (Em/Am ratio) at the septal mitral annulus (0.90 +/- 0.19 versus 0.70 +/- 0.18, p < 0.05) and the lateral mitral annulus (1.06 +/- 0.20 versus 0.86 +/- 0.14, p < 0.01) were significantly increased, while there was no significant change in the LV wall thickness after 72 weeks of therapy with Xuezhikang. The serum levels of PIP (0.43 +/- 0.13 ng/mL versus 0.51 +/- 0.20 ng/mL, p < 0.05) and CRP (0.32 +/- 0.13 mg/L versus 0.40 +/-0.17 mg/L, p < 0.05) were significantly reduced compared to placebo treatment. There was no significant correlation between changes in LV diastolic function and blood pressure or lipid profile with Xuezhikang therapy. CONCLUSION Long-term therapy with Xuezhikang improved LV diastolic function, probably mediated through antifibrotic and anti-inflammatory effects and independent of blood pressure and lipid profiles in patients with essential hypertension.
Sin3a-associated Hdac1 and Hdac2 are essential for hematopoietic stem cell homeostasis and contribute differentially to hematopoiesis

Class I histone deacetylases are critical regulators of gene transcription by erasing lysine acetylation. Targeting histone deacetylases using relative non-specific small molecule inhibitors is of major interest in the treatment of cancer, neurological disorders and acquired immune deficiency syndrome. Harnessing the therapeutic potential of histone deacetylase inhibitors requires full knowledge of individual histone deacetylases in vivo. As hematologic malignancies show increased sensitivity towards histone deacetylase inhibitors we targeted deletion of class I Hdac1 and Hdac2 to hematopoietic cell lineages. Here, we show that Hdac1 and Hdac2 together control hematopoietic stem cell homeostasis, in a cell-autonomous fashion. Simultaneous loss of Hdac1 and Hdac2 resulted in loss of hematopoietic stem cells and consequently bone marrow failure. Bone-marrow-specific deletion of Sin3a, a major Hdac1/2 co-repressor, phenocopied loss of Hdac1 and Hdac2 indicating that Sin3a-associated HDAC1/2-activity is essential for hematopoietic stem cell homeostasis. Although Hdac1 and Hdac2 show compensatory and overlapping functions in hematopoiesis, mice expressing mono-allelic Hdac1 or Hdac2 revealed that Hdac1 and Hdac2 contribute differently to the development of specific hematopoietic lineages.
Effects of treatment with LH releasing hormone before the early increase in LH secretion on endocrine and reproductive development in bull calves.

Between 6 and 20 weeks of age an early increase in LH secretion has been reported in Hereford bull calves. Delaying this early increase in LH secretion delays testicular development. This study was designed to determine whether a premature increase in LH secretion during the early postnatal period enhances testicular development. Ten age- and body weight-matched Hereford bull calves were divided into two groups. One group (n = 5) received 200 ng LH releasing hormone (LHRH) i.v. every 2 h for 14 days, between 4 and 6 weeks of age. On the basis of blood samples taken every 15 min for 10 h, mean serum LH and testosterone concentrations and LH pulse frequency were increased by LHRH treatment (P < 0.05). Serum concentrations of FSH were not significantly influenced by treatment (P > 0.05). In treated animals at 24 weeks of age, mean serum testosterone concentrations and LH pulse amplitude were increased (P < 0.05). The concentrations of spermatozoa in electroejeculates collected at 52 weeks of age were greater in LHRH-treated compared with control calves. Testicular growth was enhanced by LHRH treatment and histological evaluation of the testis at 54 weeks of age showed increased spermatogenesis and also larger numbers of Sertoli cells per tubule cross-section as a result of LHRH treatment. We conclude that treatment with LHRH before the early increase in LH secretion altered testicular development and suggest that the early increase in LH secretion in bull calves may be critical for initiating and regulating the progression of reproductive maturation.
Health Benefits of an Innovative Exercise Program for Mitochondrial Disorders

PurposeWe determined the effects of an innovative 8-wk exercise intervention (aerobic, resistance, and inspiratory muscle training) for patients with mitochondrial disease. MethodsSeveral end points were assessed in 12 patients (19–59 yr, 4 women) at pretraining, posttraining, and after 4-wk detraining: aerobic power, muscle strength/power and maximal inspiratory pressure (main end points), ability to perform activities of daily living, body composition, quality of life, and blood myokines (secondary end points). ResultsThe program was safe, with patients’ adherence being 94% ± 5%. A significant time effect was found for virtually all main end points (P ⩽ 0.004), indicating a training improvement. Similar findings (P ⩽ 0.003) were found for activities of daily living tests, total/trunk/leg lean mass, total fat mass, femoral fracture risk, and general health perception. No differences were found for blood myokines, except for an acute exertional increase in interleukin 8 at posttraining/detraining (P = 0.002) and in fatty acid binding protein 3 at detraining (P = 0.002). ConclusionsAn intervention including novel exercises for mitochondrial disease patients (e.g., inspiratory muscle training) produced benefits in numerous indicators of physical capacity and induced a previously unreported shift toward a healthier body composition phenotype.
Genetic variation in the beta‐2 adrenergic receptor is associated with chronic musculoskeletal complaints in adolescents

There is significant evidence to suggest that psychological and stress‐related factors are important predictors of the onset of chronic widespread pain (CWP) and fibromyalgia (FM). The hypothalamic‐pituitary‐adrenal axis, together with the efferent sympathetic/adrenomedullary system, influence all body organs (including muscles) during short‐ and long‐term threatening stimuli. The aim of this study was to investigate the relationship between genetic variants in adrenergic candidate genes and chronic musculoskeletal complaints (MSCs) in adolescents.
Influential factors on the survival of endothelial cells after penetrating keratoplasty

Purpose To evaluate the factors that influence the survival of corneal endothelial cells after penetrating keratoplasty. Methods We retrospectively reviewed the medical records of 83 eyes of 83 patients who had undergone penetrating keratoplasty and whose corneal endothelial cell density was more than 2000 cells/mm2 at postoperative 1 month. The patients were divided into 3 groups: keratoconus (Group 1), bullous keratopathy (Group 2), and herpetic keratitis with uveitis (Group 3), based on the underlying disease and the recipient's corneal endothelial state. We analyzed the difference of endothelial cell loss among the 3 groups and some risk factors such as preoperative glaucoma, postoperative increased intraocular pressure, graft rejection, peripheral corneal disease, and the donor trephine size. Results The corneal endothelium cell loss was significantly higher in Groups 2 and 3 than in Group 1 after 2 years. There were statistically significant differences of the rate of corneal endothelium cell loss for the eyes with preoperative glaucoma, postoperative glaucoma medication with more than 2 agents, graft rejection, and peripheral corneal disease, but the donor trephine size was not a significant factor for corneal endothelium cell loss. Conclusions For the eyes with bullous keratopathy and herpetic keratitis with uveitis, the survival rate of the endothelium was lower than that for the eyes with keratoconus. We should carefully manage patients who have risk factors such as graft rejection, peripheral corneal disease, and perioperative glaucoma to minimize the loss of corneal endothelium and to reduce graft failure after penetrating keratoplasty.
Investigation of the Three-Dimensional Architecture of the Collagen Adhesin EmaA of Aggregatibacter actinomycetemcomitans by Electron Tomography

ABSTRACT The periodontal pathogen Aggregatibacter actinomycetemcomitans displays on the bacterial surface a nonfimbrial adhesin, EmaA, which is required for collagen binding. In this study, electron tomography was used to characterize the three-dimensional (3D) architecture of this adhesin. The antenna-like surface appendages, corresponding to EmaA, were found to be composed of an ellipsoidal domain capping a rod-like domain that adopts either a straight or a bent conformation at various positions along the length. The most common flexible point along the length of the EmaA appendage was localized 29.4 nm away from the distal end. One-fifth of the appendages were straight and the remaining showed angles distributed between 140° and 170° at this location. Deletion analysis mapped this bend to amino acids 611 to 640 of the protein sequence. The 3D structure of the collagen binding domain of EmaA was generated by alignment and averaging of 9 subvolumes of the adhesin extracted from tomograms. The structure contains three subdomains: a globular structure with a diameter of ∼5 nm and a cylindrical domain (∼4.4 nm by 5.8 nm) separated by a linker region with a diameter of ∼3 nm, followed by a cylindrical domain (∼4.6 nm by 6.6 nm). This is the first 3D structure of a trimeric autotransporter protein of A. actinomycetemcomitans.
Dielectric properties of palm oils as liquid insulating materials: effects of fat content

For transmitting a huge amount of electric power, transformer is one of the most important apparatuses. Liquid insulating materials are usually used in medium as well as high voltage transformers. Since long ago, petroleum-based mineral oils have been used as liquid insulating materials. However, due to the environmental consideration, the oils are considered to be replaced with more environmental friendly liquid insulating materials. Many researchers are now searching new types of insulating materials, which are generally organic types and obtained from the nature. The new insulating materials are biodegradable and friendly to environment. In attempt to find the new type of liquid insulating materials, we have investigated the dielectrics properties of palm oil. The samples used are RBDPO (refined, bleached and deodorized palm oils) with various content of fat (lipid). The losses factors and breakdown voltages of the oils as function of temperature and fat content were investigated. The values of flash point and viscosity as function of temperature and fat content are presented. The dependences of oil properties on the fat content were investigated. The experimental results showed that the fat content strongly affected the dielectric properties of the oils. In general, the dielectric properties improved as the fat content is reduced. The dielectric strength increased significantly as the fat content dropped to about 1 %.
Affect and automatic mood maintenance q

The hedonic contingency model (HCM; Wegener & Petty, 1994) states that individuals have learned to seek out positive activities while in a happy mood in order to maintain or elevate that mood. We argue that this tendency may become overlearned and, thus, automated. More specifically, the experience of a happy mood was predicted to automatically activate the mood-maintenance tendency proposed by the HCM. Participants induced into happy, sad, or neutral moods ranked their preferences for future activities that were nonconsciously associated with either a positive or negative valence. Supporting the notion of automatic mood maintenance, happy participants appeared to evaluate the affective qualities of the future activities and base their preferences on this evaluation without realizing that they were doing so. Theoretical implications of this finding are discussed. 2003 Published by Elsevier Science Inc.
Characterization and molecular cloning of a flavoprotein catalyzing the synthesis of phytofluene and zeta-carotene in Capsicum chromoplasts.

In plants, zeta-carotene is the first visible carotenoid formed in the biosynthetic pathway through the following two-step desaturation reaction: phytoene-->phytofluene--> zeta-carotene. Using Capsicum annuum chromoplast membranes and the reconstitution system previously described [Camara, B. , Bardat, F. & Monéger, R. (1982) Eur. J. Biochem. 127, 255-258], we have attempted to purify the desaturase(s) catalyzing these reactions. The two activities were coincidental during all the purification procedures. Only a single polypeptide with 56 +/- 2 kDa was detected by SDS/PAGE of all active fractions. The enzyme contained protein-bound FAD. Antibodies raised against the purified polypeptide selectively precipitated the phytoene and the phytofluene desaturase activities, thus demonstrating that the enzyme is a bifunctional flavoprotein. The antibodies were used to isolate a full-length cDNA clone from which was deduced the primary structure of the desaturase which contains a characteristic dinucleotide-binding site. Overexpression of the cDNA in Escherichia coli allowed the production of a recombinant desaturase which had all the properties of the chromoplast desaturase. The phytoene/phytofluene desaturase mRNA levels were extremely low in green fruits and increased slightly before detectable carotenoid synthesis and remained constant throughout ripening. However, the desaturase activity and protein levels were found to increase significantly during the chloroplast to chromoplast transition in C. annuum fruits.
Effect of caponization on performance and quality characteristics of long bones in Polbar chickens

&NA; The effect of caponization on the mechanical properties of Polbar chicken bones was the subject of investigation. The biomechanical strength of bones and the risk of their deformation or fracture were determined on the basis of their geometric, structural, material, and densitometric properties. Eight‐week‐old cockerels of Polbar breed were surgically castrated and then fattened until the 24th week of life. It was observed that caponization did not influence the weight and length of either of the long bones. It did however significantly reduce their ash content and the Ca and P contents in their femur, and P content in their tibia. Dual energy x‐ray absorptiometry densitometry revealed that bone mineral content of the mid‐diaphyseal part of both bones were reduced. Similarly, the bone tissue density of bones decreased. Caponization influenced the bone's geometric structure increasing the internal and external diameters of the bones. The bone cross‐sectional area was greater in capons, and, consequently, the cross‐sectional moment of inertia and the radius of gyration significantly increased. However, the relative wall thickness and cortical index were not altered. The three‐point bending tests revealed the negative effect of caponization on the mechanical endurance of bones. Yield strength, Young modulus, and yield stress, characterizing the strength of the bone's material, decreased in capons. That suggests a higher risk of permanent deformation as capon bones become less elastic. Concluding, caponization negatively influenced the quality characteristics of Polbar chicken long bones.
On the consequences of placing amino groups at the TBP–DNA interface. Does TATA really matter?

The TATA‐box binding protein (TBP) belongs to a family of structural proteins involved in transcription in eukaryotic cells. TBP binds in the minor groove of DNA and recognizes specifically the consensus sequence: 5′ TATAWAWR 3′ (W = A or T). Recent reports show that the TATA‐box is only present in 10% of all human polymerase II promoters. Therefore, TBP must bind frequently to low affinity DNA sequences, possibly with help of other transcription factors. In order to understand the intramolecular and intermolecular interactions that lead to the consensus sequence preferred by TBP, we use high resolution crystallographic structures of cognate TBP–DNA complexes as templates onto which 16 dinucleotide repeating sequence DNA oligomers were built. The binding free energy of each complex was calculated using the Molecular Mechanics/Poisson–Boltzmann Solvent Accessible (MM‐PBSA) approximation. Parsing of the free energy components allowed us to identify the most important contributions to sequence selectivity: DNA deformation and the interaction energy between TBP residues and DNA bases, as expected. Surprisingly, poor interaction energies lead to larger deformation costs, suggesting strategies to improve affinity and selectivity. Local analysis of the TBP–DNA interface allowed us to build interaction and deformation energy tables that were used, without the need to fit their relative weights, to predict successfully both the consensus sequence for TBP, and relative binding affinities for a collection of TATA box variants. Copyright © 2009 John Wiley & Sons, Ltd.
Quality of Parental Emotional Care and Calculated Risk for Coronary Heart Disease

Objective: To evaluate associations between perceived quality of parental emotional care and calculated 10-year risk for coronary heart disease (CHD). Little is understood about the role of parental emotional care in contributing to the risk for CHD. Methods: The study sample was composed of 267 participants from the New England Family Study. Quality of parental emotional care was measured, using a validated short version of the Parental Bonding Instrument (PBI) as the average care scores for both parents (range = 0–12), with higher scores indicating greater care. Ten-year CHD risk was calculated, using the validated Framingham Risk Algorithm that incorporates the following prevalent CHD risk factors: age, sex, diabetes, smoking, total cholesterol, high-density lipoprotein cholesterol, and blood pressure. Multiple linear regression assessed associations of PBI with calculated CHD risk after adjusting for childhood socioeconomic status, depressive symptomatology, educational attainment, and body mass index. Results: Among females, a 1-unit increase in the parental emotional care score resulted in a 4.6% (p = .004) decrease in the 10-year CHD risk score, after adjusting for covariates. There was no association between parental emotional care score and calculated CHD risk score in males (p = .22). Conclusion: Quality of parental emotional care was inversely associated with calculated 10-year CHD risk in females, and not males. Although the gender differences need further investigation and these findings require replication, these results suggest that the early childhood psychosocial environment may confer risk for CHD in adulthood. CHD = coronary heart disease; PBI = parental bonding instrument; BMI = body mass index; SEP = socioeconomic position; HDL = high-density lipoprotein; CES-D = Center for Epidemiologic Studies Depression Scale.