Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic hyperammonemia in vivo impairs long‐term potentiation in hippocampus by altering activation of cyclic GMP‐dependent‐protein kinase and of phosphodiesterase 5

Long‐term potentiation (LTP) is impaired in the CA1 area of hippocampal slices from rats with chronic moderate hyperammonemia. We studied the mechanisms by which hyperammonemia in vivo impairs LTP. This process requires sequential activation of soluble guanylate cyclase, cyclic GMP‐dependent protein kinase (PKG) and cyclic GMP‐degrading phosphodiesterase. Application of the tetanus induced a rapid increase of cyclic GMP in slices from control or hyperammonemic rats, which is followed in control slices by a sustained decrease in cyclic GMP due to sustained activation of cyclic GMP‐degrading phosphodiesterase, which in turn is due to sustained activation of PKG. In slices from rats with chronic hyperammonemia tetanus‐induced decrease in cyclic GMP was delayed and transient due to lower and transient activation of PKG and of the phosphodiesterase. Hyperammonemia‐induced impairment of LTP may be involved in the alterations of cognitive function in patients with hepatic encephalopathy.
Two Independent Internal Ribosome Entry Sites Are Involved in Translation Initiation of Vascular Endothelial Growth Factor mRNA

ABSTRACT The mRNA of vascular endothelial growth factor (VEGF), the major angiogenic growth factor, contains an unusually long (1,038 nucleotides) and structured 5′ untranslated region (UTR). According to the classical translation initiation model of ribosome scanning, such a 5′ UTR is expected to be a strong translation inhibitor. In vitro and bicistronic strategies were used to show that the VEGF mRNA translation was cap independent and occurred by an internal ribosome entry process. For the first time, we demonstrate that two independent internal ribosome entry sites (IRESs) are present in this 5′ UTR. IRES A is located within the 300 nucleotides upstream from the AUG start codon. RNA secondary structure prediction and site-directed mutagenesis allowed the identification of a 49-nucleotide structural domain (D4) essential to IRES A activity. UV cross-linking experiments revealed that IRES A activity was correlated with binding of a 100-kDa protein to the D4 domain. IRES B is located in the first half of the 5′ UTR. An element between nucleotides 379 and 483 is required for its activity. Immunoprecipitation experiments demonstrated that a main IRES B-bound protein was the polypyrimidine tract binding protein (PTB), a well-known regulator of picornavirus IRESs. However, we showed that binding of the PTB on IRES B does not seem to be correlated with its activity. Evidence is provided of an original cumulative effect of two IRESs, probably controlled by different factors, to promote an efficient initiation of translation at the same AUG codon.
The Human Skeletal Muscle Transcriptome in Response to Oral Shilajit Supplementation.

UNLABELLED The objective of the present study ( clinicaltrials.gov NCT02026414) was to observe the effects of oral supplementation of a purified and standardized Shilajit extract on skeletal muscle adaptation in adult overweight/class I obese human subjects from the U.S. POPULATION Shilajit is a mineral pitch that oozes out of Himalayan rocks. The study design consisted of a baseline visit, followed by 8 weeks of 250 mg of oral Shilajit supplementation b.i. d. , and additional 4 weeks of supplementation with exercise. At each visit, blood samples and muscle biopsies were collected for further analysis. Supplementation was well tolerated without any changes in blood glucose levels and lipid profile after 8 weeks of oral supplementation and the additional 4 weeks of oral supplementation with exercise. In addition, no changes were noted in creatine kinase and serum myoglobin levels after 8 weeks of oral supplementation and the additional 4 weeks of supplementation with exercise. Microarray analysis identified a cluster of 17 extracellular matrix (ECM)-related probe sets that were significantly upregulated in muscles following 8 weeks of oral supplementation compared with the expression at the baseline visit. This cluster included tenascin XB, decorin, myoferlin, collagen, elastin, fibrillin 1, and fibronectin 1. The differential expression of these genes was confirmed using quantitative real-time polymerase chain reaction (RT-PCR). The study provided maiden evidence that oral Shilajit supplementation in adult overweight/class I obese human subjects promoted skeletal muscle adaptation through upregulation of ECM-related genes that control muscle mechanotransduction properties, elasticity, repair, and regeneration.
Ocular response analyzer measurements in keratoconus with normal central corneal thickness compared with matched normal control eyes.

PURPOSE To compare corneal hysteresis (CH) and corneal resistance factor (CRF) in eyes with keratoconus with a central corneal thickness (CCT) ≥ 520 μm with CH and CRF in matched controls, and to estimate the sensitivity and specificity of these parameters for discriminating between the two groups. METHODS This prospective, comparative case series comprised 19 eyes of 19 patients with keratoconus with CCT ≥ 520 μm and 19 eyes of 19 healthy sex-, age-, and CCT-matched patients who underwent a complete clinical eye examination, corneal topography, tomography, and biomechanical evaluation. The receiver operating characteristic (ROC) curve was used to identify cutoff points that maximized the sensitivity and specificity for discriminating between groups. RESULTS Central corneal thickness was 543.1 ± 13.9 μm (range: 520 to 568 μm) in the keratoconus group and 545 ± 12.5 μm (range: 527 to 575 μm) in the control group (P=.6017). Corneal hysteresis was 9.22 ± 1.44 mmHg (range: 6.2 to 11.35 mmHg) in the keratoconus group and 10.58 ± 1.91 mmHg (range: 7.34 to 13.53 mmHg) in the control group (P=.0075). Corneal resistance factor was 8.62 ± 1.52 mmHg (range: 5.60 to 11.20 mmHg) in the keratoconus group and 10.30 ± 1.92 mmHg (range: 6.95 to 14.12 mmHg) in the control group (P=.0049). The ROC curve analyses showed a poor overall predictive accuracy of CH (cutoff, 9.90 mmHg; sensitivity, 78.9%; specificity, 63.2%; test accuracy, 71.05%) and CRF (cutoff, 8.90 mmHg; sensitivity, 68.4%; specificity, 78.9%; test accuracy, 73.65%) for detecting keratoconus in the eyes studied. CONCLUSIONS Corneal hysteresis and CRF were statistically lower in the keratoconus group compared with the control group. Given the large overlap, both CH and CRF had low sensitivity and specificity for discriminating between groups.
The Oxytocin–Vasopressin Pathway in the Context of Love and Fear

Vasopressin (VP) and oxytocin (OT) are distinct molecules; these peptides and their receptors [OT receptor (OTR) and V1a receptor (V1aR)] also are evolved components of an integrated and adaptive system, here described as the OT–VP pathway. The more ancient peptide, VP, and the V1aRs support individual survival and play a role in defensive behaviors, including mobilization and aggression. OT and OTRs have been associated with positive social behaviors and may function as a biological metaphor for social attachment or “love. ” However, complex behavioral functions, including selective sexual behaviors, social bonds, and parenting require combined activities of OT and VP. The behavioral effects of OT and VP vary depending on perceived emotional context and the history of the individual. Paradoxical or contextual actions of OT also may reflect differential interactions with the OTR and V1aR. Adding to the complexity of this pathway is the fact that OT and VP receptors are variable, across species, individuals, and brain region, and these receptors are capable of being epigenetically tuned. This variation may help to explain experience-related individual and sex differences in behaviors that are regulated by these peptides, including the capacity to form social attachments and the emotional consequences of these attachments.
Lower urinary tract symptoms and sexual dysfunction: epidemiology and pathophysiology

There is ample evidence from many epidemiological studies that lower urinary tract symptoms (LUTS) and sexual dysfunction are strongly linked, independently of age and comorbidities such as hypertension, diabetes, dyslipidaemia and coronary heart disease. However, a causal link between both conditions is not yet established. Four pathophysiological mechanisms currently support the relationship between LUTS and erectile dysfunction (ED): (i) The nitric oxide synthase (NOS)/NO theory; there is a reduction in NOS‐containing nerves in the prostate and bladder/urethra in patients with bladder outlet obstruction (BOO), and that lack of NO or loss of protein kinase G causes ED; (ii) The autonomic hyperactivity and metabolic syndrome hypothesis: benign prostatic hyperplasia (BPH) may be part of the metabolic syndrome, which includes cardiovascular diseases (e.g. hypertension, ischaemic heart disease) and diabetes mellitus, known risk factors for ED. Hypertension, obesity, and hyperinsulinaemia have all been claimed to be associated with an increased sympathetic activity. Increased sympathetic activity is involved in LUTS/BPH and may have a role in ED/sexual dysfunction, with noradrenaline and α1‐adrenoceptors representing a common link; (iii) the Rho‐kinase activation/endothelin pathway; there can be increased Rho‐kinase activity, and consequently calcium sensitivity of the contractile machinery, in prostate smooth muscle in BPH, the detrusor in BOO, corpora cavernosa in ED, and in the resistance vessels in hypertension. The actions of several factors beside noradrenaline (e.g. endothelin‐1, angiotensin II), possibly involved in the increased smooth muscle activity found in both LUTS/BPH and sexual dysfunction, are dependent on Rho‐kinase activity. Thus increased Rho‐kinase activity might represent a common link between LUTS and sexual dysfunction; (iv) Pelvic atherosclerosis; animal models mimicking pelvic ischaemia and hypercholesterolaemia show similar smooth muscle alterations of the detrusor and corpora. Pelvic ischaemia may induce the biological modifications described above and may thus represent as well a common link between LUTS and sexual dysfunction. Studies treating one condition (e.g. ED) and measuring the impact on the other (e.g. LUTS) should further contribute to support this common link.
Bistability in bacteria

Gene expression in bacteria is traditionally studied from the average behaviour of cells in a population, which has led to the assumption that under a particular set of conditions all cells express genes in an approximately uniform manner. The advent of methods for visualizing gene expression in individual cells reveals, however, that populations of genetically identical bacteria are sometimes heterogeneous, with certain genes being expressed in a non‐uniform manner across the population. In some cases, heterogeneity is manifested by the bifurcation into distinct subpopulations, and we adopt the common usage, referring to this phenomenon as bistability. Here we consider four cases of bistability, three from Bacillus subtilis and one from Escherichia coli, with an emphasis on random switching mechanisms that generate alternative cell states and the biological significance of phenotypic heterogeneity. A review describing additional examples of bistability in bacteria has been published recently.
Unemployment Evolution in Romania

The labor market occupies the main stage in the specialty literature research. One of the most important phenomenon to understand is the unemployment, having implication in many areas as sociology, demography, economics and others. The purpose of this study is to find a relationship between the unemployment rate and other economic indices: number of emigrants, number of immigrants, import, life expectancy, GDP and available population for Romania for the 1991 â€“ 2016 period.
Polymerase chain reaction–based identification of clinically relevant Pasteurellaceae isolated from cats and dogs in Poland

A set of polymerase chain reaction (PCR) assays for identification of the most important Pasteurellaceae species encountered in cats and dogs were developed. Primers for Pasteurella multocida were designed to detect a fragment of the kmt, a gene encoding the outer-membrane protein. Primers specific to Pasteurella canis, Pasteurella dagmatis, and Pasteurella stomatis were based on the manganese-dependent superoxide dismutase gene (sodA) and those specific to [Haemophilus] haemoglobinophilus on species-specific sequences of the 16S ribosomal RNA gene. All the primers were tested on respective reference and control strains and applied to the identification of 47 canine and feline field isolates of Pasteurellaceae. The PCR assays were shown to be species specific, providing a valuable supplement to phenotypic identification of species within this group of bacteria.
Detection of Experimental Hepatic Tumors Using Long Circulating Superparamagnetic Particles

Sayegh Y, Pochon S, Vallée J-P, et al. Detection of experimental hepatic tumors using long circulating superparamagnetic particles. Invest Radiol 2001;36:15–21. RATIONALE AND OBJECTIVES.To evaluate the potential of an iron oxide-based MR contrast agent for the detection and delineation of experimental liver tumors during the early vascular phase of the compound. METHODS.Superparamagnetic blood pool agent (SBPA) was administered intravenously to rabbits bearing VX2 tumors. Images were acquired before the injection, immediately after, and 1 or 3 weeks later. The variations of signal intensity were measured in the tumors and in several tissues for various T1-weighted spin-echo, T2-weighted fast spin-echo, and T2-weighted gradient-recalled-echo sequences. RESULTS.Fourteen and 12 of the 16 tumors were detected immediately after SBPA injection using, respectively, the T2-weighted fast spin-echo and T2-weighted gradient-recalled-echo sequences. A significant decrease in signal intensity was observed in well-perfused organs, and blood signal was abolished even at the lowest injected dose and using a T1-weighted sequence. In the late phase, the loss in signal intensity of the liver was even more pronounced. CONCLUSION.The dominant T2 effect of SBPA induces an increase in the tumor-to-liver and tumor-to-blood contrast during the vascular phase, improving the detection of the tumors and allowing the distinction between small lesions and vessels through plane. This effect on the liver signal persists for several days because of the incorporation of SBPA in the reticuloendothelial system.
Distributions of pI versus pH provide prior information for the design of crystallization screening experiments: response to comment on 'Protein isoelectric point as a predictor for increased crystallization screening efficiency'

MOTIVATION Increased efficiency in initial crystallization screening reduces cost and material requirements in structural genomics. Because pH is one of the few consistently reported parameters in the Protein Data Bank (PDB), the isoelectric point (pI) of a protein has been explored as a useful indirect predictor for the optimal choice of range and distribution of the pH sampling in crystallization trials. RESULTS We have analyzed 9596 unique protein crystal forms from the August 2003 PDB and have found a significant relationship between the calculated pI of successfully crystallized proteins and the difference between pI and reported pH at which they were crystallized. These preferences provide strong prior information for the design of crystallization screening experiments with significantly increased efficiency and corresponding reduction in material requirements, leading to potential cost savings of millions of US$ for structural genomics projects involving high-throughput crystallographic structure determination. AVAILABILITY A prototype example of a screen design and efficiency estimator program, CrysPred, is available at http://www-structure.llnl. gov/cryspred/
Beneficial Biochemical Outcomes of Late‐Onset Dietary Restriction in Rodents

Abstract: Dietary restriction (DR) or caloric restriction (CR) is the well‐established means to retard aging, leading to prolongation of mean and maximum life span in many animal models. We have been interested in the possibility of extending the span of health of elderly people rather than increasing longevity, and therefore studied the effects of DR/CR initiated late in life in rodent models. We restricted food for 2–3.5 months in mice or rats of middle or old ages, which would perhaps be equivalent to 50–70 years of age in humans. We found that: (1) Potentially harmful altered proteins were reduced in the animals' tissues. (2) Extended half‐life of protein in aged animals was shortened in mouse hepatocytes, suggesting improved protein turnover. (3) Reduced proteasome activity was upregulated in rat liver and skeletal muscle. (4) Protein carbonyls were decreased in rat liver mitochondria and skeletal muscle cytoplasm, and also oxidative DNA damage was reduced in rat liver nucleus, suggesting amelioration of oxidative stress. (5) Reduced apo A‐IV and C‐III metabolism in aged mouse was restored, suggesting increase in reduced fatty acid mobilization. (6) The carbonyl modification in histones that was paradoxically reduced in aged rat was increased to the level of a young animal, suggesting restoration of reduced transcription. These findings in rodents suggest a possibility that DR/CR is beneficial if applied in middle‐aged or early senescent obese people. We argue, however, that application of late life DR/CR can be harmful if practiced in people who are already eating modestly.
Injury (nociceptive afferent nerve stimulation) modifies the hemodynamic and metabolic responses to hemorrhage in immature swine

ObjectiveTo determine the effects of reinfusion of shed blood on the regional blood flow changes induced by hemorrhage and hemorrhage plus nociceptive nerve stimulation (injury) with special reference to the gut. DesignRandomized controlled laboratory study. SettingMedical Research Council laboratory, university medical school. SubjectsFour groups of anesthetized immature female Large-White pigs (15–27 kg): 30% hemorrhage, 30% hemorrhage plus afferent nerve stimulation, nerve stimulation alone, surgical controls. InterventionsIn addition to standard invasive hemodynamic monitoring, electromagnetic flow probes were placed around a branch of the superior mesenteric artery and the right femoral artery. Stimulating electrodes were placed on brachial nerves in both axillae. Animals underwent 30% hemorrhage over 30 mins. After a 30-min shock period, the shed blood was reinfused at 2 mL/kg/min. Measurements and Main ResultsMeasurements/calculations of standard global hemodynamics, gut and femoral blood flows/vascular resistance, metabolism, arterial plasma lactate, portal venous endotoxin, interleukin-6, and tumor necrosis factor-&agr; were made before and after hemorrhage, before and after reinfusion, and at 30-min intervals for 3 hrs. Blood and tissue samples were taken for the presence of translocated coliforms. Hemorrhage elicited the expected changes in global hemodynamics, metabolism, and gut and femoral blood flows. There was a partial hemodynamic recovery during the shock period. Nearly all hemodynamic and metabolic variables were rapidly restored by reinfusion. The response to hemorrhage was modified by nerve stimulation: Reductions in systemic hemodynamics and gut flow were greater, and there was no recovery during the shock phase. Cytokine and endotoxin concentrations increased significantly in all groups. There was no bacterial translocation. ConclusionsWhen hemorrhage occurs in the presence of nerve stimulation (injury), the relative protection of the gut circulation is attenuated and this effect persists after the end of hemorrhage and reinfusion. However, there was no evidence that injury increased the hemorrhage/surgery-induced cytokine and endotoxin responses.
Prevalence of chondral defects in athletes' knees: a systematic review.

PURPOSE To determine the prevalence of full-thickness focal chondral defects in the athlete's knee. METHODS We conducted a systematic review of multiple databases, evaluating studies of the prevalence of articular cartilage defects in athletes. Because of the heterogeneity of data, a meta-analysis could not be performed. RESULTS Eleven studies were identified for inclusion (931 subjects). All studies were level 4 evidence. Defects were diagnosed via magnetic resonance imaging, arthroscopy, or both. Forty percent of athletes were professionals (NBA and NFL). The overall prevalence of full-thickness focal chondral defects in athletes was 36% (range = 2.4%-75% between all studies). Fourteen percent of athletes were asymptomatic at the time of diagnosis. Patellofemoral defects (37%) were more common than femoral condyle (35%) and tibial plateau defects (25%). Medial condyle defects were more common than lateral (68% vs 32%), and patella defects were more common than trochlea (64% vs 36%). Meniscal tear (47%) was the most common concomitant knee pathological finding, followed by anterior cruciate ligament tear (30%) and then medial collateral ligament or lateral collateral ligament tear (14%). CONCLUSIONS Full-thickness focal chondral defects in the knee are more common in athletes than among the general population. More than one-half of asymptomatic athletes have a full-thickness defect. Further study is needed to define more precisely the prevalence of these lesions in this population.
Timing Matters: How Delaying College Enrollment Affects Earnings Trajectories

Over one in three students who started college in 2012 did not enroll in the fall immediately following their high school graduation. Despite the prevalence of delayed college enrollment, however, little is known about its consequences for labor market outcomes. Using data from the National Longitudinal Survey of Youth 1997, this paper examines the characteristics and earnings trajectories of students who do not enroll in college immediately after high school (“delayers”) and the effects of this choice on academic and labor market outcomes. Propensity score matching results show that delaying college enrollment decreases individuals’ likelihood of enrolling in college and increases their tendency to enroll in two-year colleges if they do return to school. They also show that, consistent with the study’s descriptive results, the early earnings benefits experienced by delayers fade out after their mid-20s and turn to significant losses over time. Oaxaca decomposition results indicate that differences in student characteristics only explain one third of the pay gap between the two groups; 60 percent of the pay gap is explained by delayers’ reduced likelihood of attending and obtaining a degree at a fouryear college.
Coenzyme Q10 Therapy

For a number of years, coenzyme Q10 (CoQ10) was known for its key role in mitochondrial bioenergetics; later studies demonstrated its presence in other subcellular fractions and in blood plasma, and extensively investigated its antioxidant role. These 2 functions constitute the basis for supporting the clinical use of CoQ10. Also, at the inner mitochondrial membrane level, CoQ10 is recognized as an obligatory cofactor for the function of uncoupling proteins and a modulator of the mitochondrial transition pore. Furthermore, recent data indicate that CoQ10 affects the expression of genes involved in human cell signaling, metabolism and transport, and some of the effects of CoQ10 supplementation may be due to this property. CoQ10 deficiencies are due to autosomal recessive mutations, mitochondrial diseases, aging-related oxidative stress and carcinogenesis processes, and also statin treatment. Many neurodegenerative disorders, diabetes, cancer, and muscular and cardiovascular diseases have been associated with low CoQ10 levels as well as different ataxias and encephalomyopathies. CoQ10 treatment does not cause serious adverse effects in humans and new formulations have been developed that increase CoQ10 absorption and tissue distribution. Oral administration of CoQ10 is a frequent antioxidant strategy in many diseases that may provide a significant symptomatic benefit.