The SMN complex drives structural changes in human snRNAs to enable snRNP assembly.

Spliceosomal snRNPs are multicomponent particles that undergo a complex maturation pathway. Human Sm-class snRNAs are generated as 3'-end extended precursors, which are exported to the cytoplasm and assembled together with Sm proteins into core RNPs by the SMN complex. Here, we provide evidence that these pre-snRNA substrates contain compact, evolutionarily conserved secondary structures that overlap with the Sm binding site. These structural motifs in pre-snRNAs are predicted to interfere with Sm core assembly. We model structural rearrangements that lead to an open pre-snRNA conformation compatible with Sm protein interaction. The predicted rearrangement pathway is conserved in Metazoa and requires an external factor that initiates snRNA remodeling. We show that the essential helicase Gemin3, which is a component of the SMN complex, is crucial for snRNA structural rearrangements during snRNP maturation. The SMN complex thus facilitates ATP-driven structural changes in snRNAs that expose the Sm site and enable Sm protein binding.

Age- and Gender-Related Differences in the Hemodynamic Status of Patients with Mild or Moderate Hypertension.

Purpose: The aim of this study was to use non-invasive impedance cardiography (ICG) to determine the hemodynamic status of patients with grade 1 and grade 2 hypertension in relation to gender and age. Patients and Methods: We analyse prospectively collected data of 158 patients with grade 1 or grade 2 arterial hypertension. Patients were grouped according to age: 1) <50 years and 2) ≥50 years. Hemodynamic status of patients was assessed by using non-invasive ICG. For the purpose of this study two hemodynamic parameters were used: a) systemic vascular resistance index (SVRI) and b) left cardiac work index (LCWI). The primary endpoint was the hemodynamic status of patients. The secondary endpoint was hypertension-mediated organ damage. Results: Increased SVRI was assessed in 80% of patients, more common in the ≥50 years group than in the <50 years group (88.5% vs 64.8%; p < 0.01). The occurrence of increased systemic vascular resistance correlates hierarchically with increasing age. Elevated LCWI (hypervolemia and/or hyperinotropy) was present in 63% of patients, more often in males than females (70.3% vs 57.1%; p < 0.05) as well in those <50 years than in older patients (70.4% vs 59.6%; p < 0.05). Patients with diabetes were less likely to have hypervolemia/hyperinotropy than those without diabetes (46.7% vs 67.2%; p < 0.01). Hypervolemia/hyperinotropy (46.7%) and hypovolemia/hypoinotropy (43.3%) were present in a similar percentage of diabetic patients. Left ventricular hypertrophy was found in 30 patients (19%). Patients with left ventricular hypertrophy were more commonly male (66.7% vs 42.2%; p = 0.016) and had increased systemic vascular resistance (96.7% vs 77.3%; p = 0.015) compared to the patients without left ventricular hypertrophy. Hypertensive retinopathy grade III was found in 14 patients (8.9%). Elevated daytime systolic pressure, diabetes and increased age are independent predictors of grade III hypertensive retinopathy. Patients with reduced renal function had higher mean systolic blood pressure (p < 0.05), were more commonly male (p < 0.01) and older (p < 0.01) than those without reduced renal function. Conclusion: Although there are certain correlations between hemodynamic disorders and age and gender, specific hemodynamic status of an individual patient with hypertension cannot reliably be predicted on the basis of age and gender. The measurement of hemodynamic parameters by ICG can guide the clinician to select appropriate antihypertensive therapy to the patients' hemodynamic pathophysiologic condition.

TSSC4 is a component of U5 snRNP that promotes tri-snRNP formation.

U5 snRNP is a complex particle essential for RNA splicing. U5 snRNPs undergo intricate biogenesis that ensures that only a fully mature particle assembles into a splicing competent U4/U6•U5 tri-snRNP and enters the splicing reaction. During splicing, U5 snRNP is substantially rearranged and leaves as a U5/PRPF19 post-splicing particle, which requires re-generation before the next round of splicing. Here, we show that a previously uncharacterized protein TSSC4 is a component of U5 snRNP that promotes tri-snRNP formation. We provide evidence that TSSC4 associates with U5 snRNP chaperones, U5 snRNP and the U5/PRPF19 particle. Specifically, TSSC4 interacts with U5-specific proteins PRPF8, EFTUD2 and SNRNP200. We also identified TSSC4 domains critical for the interaction with U5 snRNP and the PRPF19 complex, as well as for TSSC4 function in tri-snRNP assembly. TSSC4 emerges as a specific chaperone that acts in U5 snRNP de novo biogenesis as well as post-splicing recycling.

Significance of acPWV for Survival of Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: Abnormal arterial stiffness (AS) is a major complication in end-stage kidney disease (ESKD) patients treated by dialysis. Our study aimed to determine the significance of AS for survival of prevalent dialysis patients, as well as its association with cardiovascular parameters or vascular calcification promoters/inhibitors or both and AS. MATERIALS AND METHODS: The study involved 80 adult hemodialysis patients. Besides standard laboratory analyses, we also determined promoters and inhibitors of vascular calcification (bone biomarkers): serum levels of fibroblast growth factor 23 (FGF23), soluble Klotho, intact parathormone (iPTH), 1,25-dihydroxyvitamin D3, osteoprotegerin, sclerostin, AS measured as ankle carotid pulse wave velocity (acPWV), Ankle Brachial Index (ABI), and vascular calcification (VC) score. Patients were monitored for up to 28 months. According to the median acPWV value, we divided patients into a group with acPWV ≤ 8.8 m/s, and a group with acPWV > 8.8 m/s, and the two groups were compared. RESULTS: Values for bone biomarkers were similar in both groups. Mean arterial blood pressure (MAP), central systolic and diastolic brachial blood pressure, heart rate, and pulse pressure were higher in the group with acPWV > 8.8 m/s than in the group with acPWV ≤ 8.8 m/s. The mortality was higher for patients with acPWV > 8.8 m/s at any given time over 28 months of follow-up. In multivariable analysis, predictors of higher acPWV were age >60.5, higher pulse rate, and higher central systolic or brachial diastolic blood pressure. CONCLUSIONS: According to our results, we advise the measurement of acPWV preferentially in younger dialysis patients for prognosis, as well as intervention planning before the development of irreversible changes in blood vessels. In addition, measuring central systolic blood pressure seems to be useful for monitoring AS in prevalent hemodialysis patients.

Positive impact of prescribed physical activity on symptoms of schizophrenia: randomized clinical trial.

BACKGROUND: The purpose of this study was to examine functional capacity of cardio-respiratory system in patients with schizophrenia, and to evaluate the effects of 12 weeks prescribed physical activity on aerobic capacity and symptoms of schizophrenia. SUBJECTS AND METHODS: Study involved 80 hospitalized patients with any of the subtypes of schizophrenia (42 men, 38 women). They were divided into two groups: exercise and control group, both with 40 patients. Maximal aerobic capacity (VO2 max) as an indicator of cardiovascular fitness has been obtained by cardiopulmonary stress test on a treadmill. Twelve weeks program of prescribed physical activity (45 minutes, four times per week) was made for every patient individually. Patients in exercise group practiced in training zone between 65 and 75% of their maximum heart rate (HR). Target HR was controlled by Polar F4 monitors. Symptoms of schizophrenia were measured by using Positive and Negative Symptoms Scale (PANSS). RESULTS: Before the exercise program was introduced, measured VO2 max was significantly lower in patients with schizophrenia, than the expected average value in matched healthy subjects (p<0.001). After twelve weeks, patients in exercise group showed a significant increase of VO2max (p=0.002), and significantly higher level of VO2max compared to the control group (p=0.000). Significant differences were also observed on PANSS general psychopathology subscale (p=0.007) and on PANSS total score (p=0.001). The pharmacotherapy and exercise had influence on PANSS general psychopathology (p=0.002) and PANSS total score (p=0.001). CONCLUSIONS: Individuals with schizophrenia have lower levels of aerobic capacity compared to general population. Prescribed physical activity significantly improves aerobic capacity in people with schizophrenia and it is effective in amelioration of some psychiatric symptoms. Prescribed physical activity could be an effective adjunctive treatment for patients with schizophrenia, not only for prevention and treatment of comorbidities, but also having an impact on symptoms of schizophrenia.

Effect of Astaxanthin Supplementation on Salivary IgA, Oxidative Stress, and Inflammation in Young Soccer Players.

The physiologic stress induced by physical activity is reflected in immune system perturbations, oxidative stress, muscle injury, and inflammation. We investigated the effect of astaxanthin (Asx) supplementation on salivary IgA (sIgA) and oxidative stress status in plasma, along with changes in biochemical parameters and total/differential white cell counts. Forty trained male soccer players were randomly assigned to Asx and placebo groups. Asx group was supplemented with 4 mg of Asx. Saliva and blood samples were collected at the baseline and after 90 days of supplementation in preexercise conditions. We observed a rise of sIgA levels at rest after 90 days of Asx supplementation, which was accompanied with a decrease in prooxidant-antioxidant balance. The plasma muscle enzymes levels were reduced significantly by Asx supplementation and by regular training. The increase in neutrophil count and hs-CRP level was found only in placebo group, indicating a significant blunting of the systemic inflammatory response in the subjects taking Asx. This study indicates that Asx supplementation improves sIgA response and attenuates muscle damage, thus preventing inflammation induced by rigorous physical training. Our findings also point that Asx could show significant physiologic modulation in individuals with mucosal immunity impairment or under conditions of increased oxidative stress and inflammation.

Hematological and Biochemical Parameters in Elite Soccer Players During A Competitive Half Season.

BACKGROUND: The purpose of the present study was to report and discuss the hematological and biochemical behavior of elite soccer players, in order to get more insight in the physiological characteristics of these sportsmen and to provide trainers and sports doctors with useful indicators. METHODS: Nineteen male soccer players volunteered to participate in this study. We followed the young elite soccer players during a competitive half season. Venous blood samples were collected between 9:00 and 10:00 a.m. after an overnight fast (10 h) at baseline, after 45 and 90 days and hematological and biochemical parameters were measured. RESULTS: Hemoglobin and hematocrit levels were significantly reduced over the observational period (p<0.05), but erythrocyte count and iron levels remained unchanged. Bilirubin and ferritin levels significantly increased in response to regular soccer training (p<0.05). We observed a significant decrease in muscle enzyme plasma activity during the 90 days study period. ANOVA analysis revealed a significant increase in the leukocyte and neutrophil counts (p<0.05), in parallel with a significant decrease in the lymphocyte count (p<0.05) after the observational period of 90 days. CONCLUSIONS: Elite soccer players are characterized by significant changes in biochemical and hematological parameters over the half season, which are linked to training workload, as well as adaptation induced by the soccer training. Although the values of the measured parameters fell within the reference range, regular monitoring of the biochemical and hematological parameters is fundamental for the identification of a healthy status and related optimal performances by sport doctors and trainers and selection of a correct workload by trainers.

Effect of astaxanthin supplementation on paraoxonase 1 activities and oxidative stress status in young soccer players.

The purpose of the study was to examine the effects of astaxanthin (Asx) on paraoxonase (PON1) activities and oxidative stress status in soccer players. Forty soccer players were randomly assigned in a double-blind fashion to Asx and placebo (P) group. Blood samples were obtained before, 45 and 90 days after supplementation. PON1 activity was assessed by using two substrates: paraoxon and diazoxon. The oxidative stress biomarkers were also examined: total sulphydryl group content (-SH groups), thiobarbituric acid-reactive substances (TBARS), advanced oxidation protein products and redox balance. The significant interaction effect of supplementation and training (p < 0.05) on PON1 activity toward paraoxon was observed. The PON1 activity toward diazoxon increased in Asx group after 90 days (p < 0.01), while there was no significant difference in P group. SH groups content rose from pre- to post-supplementation period only in Asx group (supplementation and training, p < 0.05; training, p < 0.01). TBARS levels decreased after 45 days and increased after 90 days of regular soccer training in both groups (training, p < 0.001). Redox balance decreased significantly in response to the regular training, regardless of treatment group (training, p < 0.001). Asx supplementation might increase total SH groups content and improve PON1 activity through protection of free thiol groups against oxidative modification.

[Myocardial performance index: prediction and monitoring of remodeling and functioning of the left ventricle after first myocardial infarction].

INTRODUCTION: Dynamic changing of left ventricular geometry and contractile state after acute myocardial infarction is responsible for various aspects of left ventricular remodeling and dysfunction. A number of studies have shown that myocardial performance index allows prediction of acute myocardial infarction complications. The objective of our study was to determine the power of myocardial performance index to predict and assess the severity of left ventricular remodeling, systolic and diastolic dysfunction after acute myocardial infarction over the long term. MATERIAL AND METHODS: Echocardiography was performed within the first week of hospitalization, after one, three and six months in 77 patients with first acute myocardial infarction. At the end of the study the patients were divided into group A and B with mild and severe left ventricular remodeling, respectively. RESULTS: Myocardial performance index was significantly lower in group A compared to B, at the beginning (0.62 vs. 0.75; p = 0.002), and at the end of study (0, 60 vs. 0, 69; p = 0.004). After six months, 31% of study patients developed LV systolic dysfunction with prevalence in group B (56% vs. 19%, p = 0.002). Myocardial performance index > or = 0.70 at first week after acute myocardial infarction is a strong predictive parameter for extensive early and late left ventricular remodeling and systolic dysfunction (p < 0.05), but it is not a valuable predictor of diastolic failure. DISCUSSION AND CONCLUSIONS: MPI obtained at first week of acute myocardial infarction was predictive for early and long term left ventricular remodeling and systolic dysfunction. Myocardial performance index had doubtful clinical use in assessing dynamics of remodeling and it was without clinical value in predicting diastolic function deterioration.

Velocity propagation of early diastole is a valuable tool for left ventricular remodelling after the first myocardial infarction.

PURPOSE: Velocity propagation (Vp) of early diastole is a known method for the evaluation of left ventricular (LV) diastolic function. Our purpose was to determine whether Vp is a valuable tool to characterize patients after acute myocardial infarction and LV remodelling (LVR). METHODS: M-mode, two-dimensional and Doppler echocardiography were performed in 71 patients within the first 2 days, 1, 3 and 6 months after acute myocardial infarction. We measured the left atrium, LV diameters and volumes, peak early and late velocity (E, A) deceleration time, Vp, annular velocity (e) and calculated E/e. The patients were divided in two groups: (A) without early LVR (n=39) and (B) with early LVR (n=32). RESULTS: In the first evaluation, Vp was similar in both groups (36.37 vs. 35.49 cm/s, P=0.513). Late LVR (LLVR) (44%) had developed in patients from group A with significantly lower early Vp compared with patients without LLVR (31.52 vs. 40.12 cm/s, P=0.001), with persist values even after 6 months (29.41 vs. 40.85 cm/s, P=0.001). The values of Vp were similar in the first 2 days in patients from group B with developing (78%) and nondeveloping LLVR (35.29 vs. 36.60 cm/s, P=0.614). Differences became significant after 6 months (31.71 vs. 41.80 cm/s, P=0.001). The values of Vp of 35 cm/s or less from the first week in both groups correlated with LLVR (B=3.27, P=0.015). Changing of LV volumes significantly correlated with Vp; for end-diastolic volume/body surface area (r=0.21, P=0.041) and end-systolic volume/body surface area (r=0.30, P=0.014). CONCLUSION: In this study, Vp was the only valuable Doppler echocardiographic tool that reflected early LVR and LLVR.