Age at maturity of some fish species distributed in Turkish marine waters (Actinopterygii and Elasmobranchii)

We collected data on the age at maturity (t_m) and maximum reported age (t_max) for 153 stocks of marine fishes in Turkey, belonging to 59 species, 24 families and 2 classes (Actinopterygii and Elasmobranchii). Among Actinopterygii t_m had an average of 1.8 years (1 to 4 years) while among Elasmobranchii it had an average of 11.9 years (2 to 11.9 years). Overall, t_max ranged between two years (for Sarda sarda) and 34 years (for Squalus acanthias). Mean t_max was found to be 6.24 years for Actinopterygii and 10.11 years for Elasmobranchii. t_m showed a positive linear correlation with t_max for both Actinopterygii and Elasmobranchii. Mean t_m?t_max did not differ significantly with sex within the Actinopterygii and Elasmobranchii. The ratio t_m?t_max was found to be significantly lower for Actinopterygii than for Elasmobranchii.     

Decreased binding capacity (B max) of muscarinic acetylcholine receptors in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD)

Monoaminergic dysregulation is implicated in attention-deficit/hyperactivity disorder (ADHD), and methylphenidate and amphetamines are the most frequently prescribed pharmacological agents for treating ADHD. However, it has recently been proposed that the core symptoms of the disorder might be due to an imbalance between monoaminergic and cholinergic systems. In this study, we used fibroblast cell homogenates from boys with and without ADHD as an extraneural cell model to examine the cholinergic receptor density, that is, muscarinic acetylcholine receptors (mAChRs). We found that the binding capacity (B _max) of [³H] Quinuclidinyl benzilate (³H-QNB) to mAChRs was decreased by almost 50 % in the children with ADHD (mean = 30.6 fmol/mg protein, SD = 25.6) in comparison with controls [mean = 63.1 fmol/mg protein, SD = 20.5, p ≤ 0.01 (Student’s unpaired t test)]. The decreased B _max indicates a reduced cholinergic receptor density, which might constitute a biomarker for ADHD. However, these preliminary findings need to be replicated in larger ADHD and comparison cohorts.     

Blood Flow of the Acral Finger Arterioles in Patients With Type 2 Diabetes by Quality Doppler Profiles

Patients with diabetes mellitus exhibit peripheral arterioles lesions that is associated with reduced blood flow. Here, we intended to assess the acral arterioles lesion in patients with type 2 diabetes based on the rate of blood flow by multigate spectral Doppler ultrasonography. Fifty-two patients with type 2 DM were divided into two groups. Group 1 included 13 men and 12 women with an average age of 60.60 ± 14.03 years and a duration of type 2 diabetes for 2.44 ± 1.50 years. Group 2 included 17 men and 11 women with an average age of 64.25 ± 10.84 years and type 2 diabetes for 12.57 ± 6.26 years. Age-matched control subjects (n = 52) were recruited (30 men and 22 woman, mean age of 61.19 ± 10.38 years). A multigate spectral Doppler algorithm was applied to the acral finger of the thumb of the right hand to test the arteriole diameter and hemodynamic parameters, including diameter of the acral finger arterioles (D), area of the blood flow profile of the acral finger arterioles (A _max) and hemodynamic parameters. Patients with diabetes exhibited a significant reduction in the arteriole diameter (1.63 ± 0.18 and 1.57 ± 0.22 mm, respectively, P < 0.001 for both) compared to control subjects (2.09 ± 0.17 mm). A _max were significantly reduced in patients with diabetes (61.35 ± 10.66 mm²/s for group 1 and 46.50 ± 6.59 mm²/s for group 2, P < 0.001 for both) compared to that in control subjects (77.93 ± 12.37 mm²/s). Furthermore, a significant difference in Amax was found between group 1 and group 2 (P < 0.001). The vascular resistance index (RI) was significantly higher in both patient groups 0.58 ± 0.06 for group 1 (P < 0.001) and 0.64 ± 0.07 for group 2 (P < 0.001) than that in control subjects (0.48 ± 0.04). The RI value of the acral finger arterioles differed significantly between group 1 and group 2 (P < 0.01). Diabetic patients exhibited a weak blood flow in the acral finger arterioles. The multigate spectral Doppler technology can be used to test blood flow in the acral finger arterioles and provide hemodynamic data for systematic analyses of the peripheral arteriole lesions in diabetes.     

Characterization of the Erythrocyte Sodium-Lithium Countertransporter: Limitations and Assumptions of Traditional and Kinetic Methodologies

The present work examined the key elements featuring in the various methods used to characterize the erythrocyte sodium-lithium countertransport. Effects of medium composition on lithium efflux were investigated in 20 subjects. Mean lithium efflux (mmol Li/l RBC.h) into a 150 mm sodium medium was significantly higher than efflux into a revised sodium-rich medium (149 mm) containing 1 mm Mg (0.335 ± 0.100 vs. 0.298 ± 0.085 respectively; P < 0.03). Mean lithium efflux into sodium-free media where sodium had been entirely replaced by magnesium, was significantly lower than efflux into a choline-based medium containing only 1 mm magnesium (0.088 ± 0.027 vs. 0.109 ± 0.034 respectively; P= 0.03). Sodium-lithium countertransport activity and the transporter's kinetic profile were measured simultaneously in 35 subjects using traditional choline-based and kinetic methodologies. There was a significant correlation between countertransport activity and maximal rate of turnover (V _max) (r= 0.62; P < 0.001); V _max values were consistently greater than their corresponding countertransport activities (P < 0.001). On subdividing the subject group into tertiles based on the Michaelis-Menten constant (k _m ) values (mm), <75, 75 − 150 and >150, the slopes of the regression lines for each group diminished progressively (0.64, 0.49 and 0.23 respectively), correlations within each group remained significant (P < 0.001, P < 0.001 and P < 0.02). No significant correlation was found between k _m values and countertransport activity (r= 0.035; P=ns). Increasing the number of points representing sodium concentrations within the range 0–150 mm, improved the confidence in the emerging estimates of V _max and k _m obtained by linear transformation. Comparison of kinetic data derived using four different analytical methods (two linear transformations, a nonlinear regression and a statistical method), showed no significant differences between the estimates yielded for either V _max (P= 0.88, ns) or k _m (P= 0.92, ns). This study has highlighted the critical roles of assay conditions and derivation techniques used when measuring sodium-lithium countertransport, emphasizing the need for standardization of the methodology. Received: 10 December 1996/Revised: 2 October 1997     

Is high prevalence of vitamin D deficiency a correlate for attention deficit hyperactivity disorder?

The aim of the study was to determine the association between vitamin D and attention deficit hyperactivity disorder (ADHD), and difference in the level of vitamin D in ADHD children and control. This a case–control study carried out in school health and primary health care clinics. A total of 1,331 children and adolescents who were diagnosed with ADHD based on clinical criteria and standardized questionnaires were enrolled in this study and were matched with 1,331 controls, aged 5–18 years old. Data on body mass index (BMI), clinical biochemistry variables including serum 25-hydroxyvitamin D were collected. The study found significant association between ADHD and vitamin D deficiency after adjusting for BMI and sex (adj. OR 1.54; 95 % CI 1.32–1.81; P < 0.001). Majority of the ADHD children were in the age group 5–10 years (40.7 %), followed by 11–13 years (38.4 %). The proportion of BMI <85th percentile was significantly over represented in ADHD group as compared to healthy control (87.8 vs. 83 %; P < 0.001, respectively), while on the other hand, BMI >95th percentile was over represented in the control than ADHD group (7.6 vs. 4.6 %; P < 0.001, respectively). Mean values of vitamin D (ng/mL) were significantly lower in ADHD children (16.6 ± 7.8) than in healthy children (23.5 ± 9.0) (P < 0.001). There was significant correlation between vitamin D deficiency and age (r = ?0.191, P = 0.001); calcium (r = 0.272, P = 0.001); phosphorous (r = 0.284, P = 0.001); magnesium (r = 0.292, P = 0.001); and BMI (r = 0.498, P = 0.001) in ADHD children. The vitamin D deficiency was higher in ADHD children compared to healthy children.     

A role for membrane transport in modulation of intramuscular free glutamine turnover in streptozotocin diabetic rats

We wished to examine the effects of diabetes on muscle glutamine kinetics. Accordingly, female Wistar rats (200 g) were made diabetic by a single injection of streptozotocin (85 mg/kg) and studied 4 days later; control rats received saline. In diabetic rats, glutamine concentration of gastrocnemius muscle was 33% less than in control rats: 2.60 ± 0.06 μmol/g vs. 3.84 ± 0.13 μmol/g (P < 0.001). In gastrocnemius muscle, glutamine synthetase activity (V_max) was unaltered by diabetes (approx. 235 nmol/min per g) but glutaminase V_max increased from 146 ± 29 to 401 ± 94 nmol/min per g; substrate K_m values of neither enzyme were affected by diabetes. Net glutamine efflux (AZ concentration difference × blood flow) from hindlimbs of diabetic rats in vivo was greater than control values (?30.0 ± 3.2 vs. ?1.9 ± 2.6 nmol/min per g (P < 0.001) and hindlimb NH₃ uptake was concomitantly greater (about 27 nmol/min per g). The glutamine transport capacity (V_max) of the Na-dependent System N^m in perfused hindlimb muscle was 29% lower in diabetic rats than in controls (820 ± 50 vs. 1160 ± 80 nmol/min per g (P < 0.01)), but transporter K_m was the same in both groups (9.2 ± 0.5 nM). The difference between inward and net glutamine fluxes indicated that glutamine efflux in perfused hindlimbs was stimulated in diabetes at physiological perfusate glutamine (0.5 mM); ammonia (1 mM in perfusate) had little effect on net glutamine flux in control and diabetic muscles. In Intramuscular Na⁺ was 26% greater in diabetic (13.2 μmol/g) than control muscle, but muscle K⁺ (100 μmol/g) was similar. The accelerated rate of glutamine release from skeletal muscle and the lower muscle free glutamine concentration observed in diabetes may result from a combination of; (i), a diminished Na⁺ electrochemical gradient (i.e., the net driving force for glutamine accrual in muscle falls); (ii), a faster turnover of glutamine in muscle and (iii), an increased V_max/K_m for sarcolemmal glutamine efflux.     

Isolation and characterisation of two chymotrypsins from the midgut of Locusta migratoria

Two chymotrypsin isozymes (CTR 1 and CTR 2) from the midgut lumen of Locusta migratoria have been identified and purified. MALDI-TOF mass spectrometry revealed an M_r of 22 679 (±30) for CTR 1 and 22 592 (±30) for CTR 2. Both chymotrypsins hydrolysed S-(Ala)₂ProPhe-pNA (CTR 1: K_m=0.29±0.01 mM, V_max=83.0±1.4 U/mg; CTR 2: K_m=0.42±0.01 mM, V_max=48.9±1.1 U/mg) and S-(Ala)₂ProLeu-pNA (CTR 1: K_m=0.50±0.04 mM, V_max=1.7±0.1 U/mg; CTR 2: K_m=1.12±0.08 mM, V_max=11.4±0.6 U/mg), but neither enzyme hydrolysed BTpNA, S-Phe-pNA, Ac-Leu-pNA or S-(Ala)₃-pNA. CTR 1 and CTR 2 activities were effectively inhibited by AEBSF, PMSF, TPCK, chymostatin, SBTI and BPTI. Using S-(Ala)₂ProPhe-pNA as the substrate, CTR 1 gave optimal activity between pH 8.0 and 10.0, while CTR 2 was optimally active over the range pH 8.0–11.0. The N-terminal 15 amino acids of the purified chymotrypsins were determined, revealing their unique sequences which are also different from another, previously characterised Locusta chymotrypsin.     

Changeability of sperm chromatin structure during liquid storage of ovine semen in milk-egg yolk- and soybean lecithin-based extenders and their relationships to field-fertility

The aim of this experiment was to study the effect of semen extender on sperm chromatin structure and to correlate chromatin integrity with field-fertility of preserved ram semen. Ejaculates of at least 2 × 10⁹ sperm/ml and 70 % progressive motility were collected using an artificial vagina from Chios rams (n = 11, 4–6 years old), split-diluted to 1 × 10⁹ sperm/ml with milk-egg yolk- and soybean lecithin (Ovixcell^®)-based extenders, packaged in 0.5-ml straws and examined after 6, 24 and 48 h of storage at 5 ± 1 °C. Evaluation endpoints were computer-assisted sperm motion analysis, fluorescence-based analysis of chromatin structure by chromomycin A₃ and acridine orange assays, and 65-day pregnancy rate (PR) of 34- to 36-h preserved semen after intra-cervical insemination of ewes (n = 154) in progestagen-synchronized estrus. Neither extender nor storage time had any influence on incidence of decondensed chromatin. Unlike Ovixcell^® extender, deterioration of sperm motility (P < 0.01) and chromatin stability (P < 0.005) was detected after 48 h of storage in milk-egg yolk extender. Sperm motility accounted for 14.4–18.5 % of variations in chromatin integrity (P < 0.001). No significant difference was found in PR of Ovixcell^®- and milk-egg yolk-stored semen. Nevertheless, PR differed between rams (14.3–71.4 %; P < 0.025). Chromatin integrity explained 10.2–56.3 % of variations in PR (P < 0.05–0.01). A pronounced decline in PR (19.1 %) was observed when percentages of decondensed and destabilized chromatin have reached thresholds of 10.5–30 % and 4–9 %, respectively. In conclusion, Ovixcell^® is superior to milk-egg yolk extender in preserving chromatin stability and motility. Chromatin defects are negatively associated with sperm fertility.     

Swainsonine,a novel fungal metabolite: optimization of fermentative production and bioreactor operations using evolutionary programming

The optimization of bioreactor operations towards swainsonine production was performed using an artificial neural network coupled evolutionary program (EP)-based optimization algorithm fitted with experimental one-factor-at-a-time (OFAT) results. The effects of varying agitation (300–500 rpm) and aeration (0.5–2.0 vvm) rates for different incubation hours (72–108 h) were evaluated in bench top bioreactor. Prominent scale-up parameters, gassed power per unit volume (P _g/V _L, W/m³) and volumetric oxygen mass transfer coefficient (K _L a, s^?1) were correlated with optimized conditions. A maximum of 6.59 ± 0.10 μg/mL of swainsonine production was observed at 400 rpm-1.5 vvm at 84 h in OFAT experiments with corresponding P _g/V_L and K _L a values of 91.66 W/m³ and 341.48 × 10^?4 s^?1, respectively. The EP optimization algorithm predicted a maximum of 10.08 μg/mL of swainsonine at 325.47 rpm, 1.99 vvm and 80.75 h against the experimental production of 7.93 ± 0.52 μg/mL at constant K _L a (349.25 × 10^?4 s^?1) and significantly reduced P _g/V _L (33.33 W/m³) drawn by the impellers.     

Staying close to home? Genetic differentiation of rough-toothed dolphins near oceanic islands in the central Pacific Ocean

Rough-toothed dolphins have a worldwide tropical and subtropical distribution, yet little is known about the population structure and social organization of this typically open-ocean species. Although it has been assumed that pelagic dolphins range widely due to the lack of apparent barriers and unpredictable prey distribution, recent evidence suggests rough-toothed dolphins exhibit fidelity to some oceanic islands. Using the most comprehensively extensive dataset for this species to date, we assess the isolation and interchange of rough-toothed dolphins at the regional and oceanic scale within the central Pacific Ocean. Using mtDNA and microsatellite genotyping (nDNA), we analyzed samples of insular communities from the main Hawaiian (Kaua‘i n = 93, O‘ahu n = 9, Hawai‘i n = 57), French Polynesian (n = 70) and Samoan (n = 16) archipelagos, and pelagic samples off the Northwestern Hawaiian Islands (n = 18). An overall AMOVA indicated strong genetic differentiation among islands (mtDNA F_ST = 0.265; p < 0.001; nDNA F_ST = 0.038; p < 0.001), as well as among archipelagos (mtDNA F_ST = 0.299; p < 0.001; nDNA F_ST = 0.055; p < 0.001). Shared haplotypes (n = 4) between the archipelagos may be a product of a relatively recent divergence and/or periodic exchange from poorly understood pelagic populations. Analyses using STRUCTURE and GENELAND identified four separate management units among archipelagos and within the Hawaiian Islands. These results confirm the presence of multiple insular populations within the Pacific and island-specific genetic isolation among populations attached to islands in each archipelago. Insular populations seem most prevalent where oceanographic conditions indicate high local productivity or a discontinuity with surrounding oligotrophic areas. Our findings have important implications for a little studied species that faces increasing anthropogenic threats around oceanic islands.     

Genetic diversity and genetic structure in wild populations of Mexican oregano (Lippia graveolens H.B.K.) and its relationship with the chemical composition of the essential oil

Mexican oregano is an aromatic plant traditionally harvested from wild populations by rural communities; however, there is little information about population genetics aspects of this species. Moreover, considering that the variation in essential oil production of aromatic plants has been attributed to several environmental as well as genetic factors, in this study we estimated the genetic diversity and genetic structure from 14 wild populations of L. graveolens located in four different bioclimatic regions in southeastern Mexico using AFLP markers. The overall genetic diversity of L. graveolens described as the percentage of polymorphic loci (PPL = 60.9 %) and Nei’s gene diversity (H _j  = 0.17) was moderate, but not associated with the bioclimatic conditions. Genetic variation was analyzed at chemotype and population levels. Regarding chemotypes, thymol had the highest genetic diversity (PPL = 82.8 % and H _j  = 0.22). PCoA revealed that chemotypes exhibit a certain level of genetic differentiation. Maximum parsimony dendrogram showed a grouping of individuals with a predominant chemotype. Bayesian analyses revealed a low, but significant differentiation among chemotypes (θ _ΙΙ = 0.008). Regarding populations, gene diversity showed significant differences (F _13,1204 = 22.8, P < 0.001); populations dominated by individuals from the thymol chemotype showed the highest gene diversity (H _j  = 0.31–0.25), while populations with exclusively sesquiterpene chemotype showed the lowest value (H _j  = 0.058). Cluster and Bayesian analyses (θ _ΙΙ = 0.027) revealed a low level of genetic differentiation among populations. Correlation analysis showed a significant association between the distance matrices based on the genetic markers (AFLP) and chemical compounds of essential oil (r = 0.06, P < 0.001). Our results suggest an important genetic influence on the observed chemical profiles. Nevertheless, other biotic and abiotic environmental pressures also play an important role in determining the chemotype and structure found in this aromatic species.     

A Matched-Filter-Based Algorithm for Subcellular Classification of T-System in Cardiac Tissues

In mammalian ventricular cardiomyocytes, invaginations of the surface membrane form the transverse tubular system (T-system), which consists of transverse tubules (TTs) that align with sarcomeres and Z-lines as well as longitudinal tubules (LTs) that are present between Z-lines in some species. In many cardiac disease etiologies, the T-system is perturbed, which is believed to promote spatially heterogeneous, dyssynchronous Ca²⁺ release and inefficient contraction. In general, T-system characterization approaches have been directed primarily at isolated cells and do not detect subcellular T-system heterogeneity. Here, we present MatchedMyo, a matched-filter-based algorithm for subcellular T-system characterization in isolated cardiomyocytes and millimeter-scale myocardial sections. The algorithm utilizes “filters” representative of TTs, LTs, and T-system absence. Application of the algorithm to cardiomyocytes isolated from rat disease models of myocardial infarction (MI), dilated cardiomyopathy induced via aortic banding, and sham surgery confirmed and quantified heterogeneous T-system structure and remodeling. Cardiomyocytes from post-MI hearts exhibited increasing T-system disarray as proximity to the infarct increased. We found significant (p < 0.05, Welch’s t-test) increases in LT density within cardiomyocytes proximal to the infarct (12 ± 3%, data reported as mean ± SD, n = 3) versus sham (4 ± 2%, n = 5), but not distal to the infarct (7 ± 1%, n = 3). The algorithm also detected decreases in TTs within 5° of the myocyte minor axis for isolated aortic banding (36 ± 9%, n = 3) and MI cardiomyocytes located intermediate (37 $\pm$ 4%, n = 3) and proximal (34 ± 4%, n = 3) to the infarct versus sham (57 ± 12%, n = 5). Application of bootstrapping to rabbit MI tissue revealed distal sections comprised 18.9 ± 1.0% TTs, whereas proximal sections comprised 10.1 ± 0.8% TTs (p < 0.05), a 46.6% decrease. The matched-filter approach therefore provides a robust and scalable technique for T-system characterization from isolated cells through millimeter-scale myocardial sections.     

In Vitro Functional Characterisation of Cytochrome P450 (CYP) 2C19 Allelic Variants <Emphasis Type="Italic">CYP2C19*23</Emphasis> and <Emphasis Type="Italic">CYP2C19*24</Emphasis>

Cytochrome P450 (CYP) 2C19 is essential for the metabolism of clinically used drugs including omeprazole, proguanil, and S-mephenytoin. This hepatic enzyme exhibits genetic polymorphism with inter-individual variability in catalytic activity. This study aimed to characterise the functional consequences of CYP2C19*23 (271 G>C, 991 A>G) and CYP2C19*24 (991 A>G, 1004 G>A) in vitro. Mutations in CYP2C19 cDNA were introduced by site-directed mutagenesis, and the CYP2C19 wild type (WT) as well as variants proteins were subsequently expressed using Escherichia coli cells. Catalytic activities of CYP2C19 WT and those of variants were determined by high performance liquid chromatography-based essay employing S-mephenytoin and omeprazole as probe substrates. Results showed that the level of S-mephenytoin 4′-hydroxylation activity of CYP2C19*23 (V _max 111.5 ± 16.0 pmol/min/mg, K _m 158.3 ± 88.0 μM) protein relative to CYP2C19 WT (V _max 101.6 + 12.4 pmol/min/mg, K _m 123.0 ± 19.2 μM) protein had no significant difference. In contrast, the K _m of CYP2C19*24 (270.1 ± 57.2 μM) increased significantly as compared to CYP2C19 WT (123.0 ± 19.2 μM) and V _max of CYP2C19*24 (23.6 ± 2.6 pmol/min/mg) protein was significantly lower than that of the WT protein (101.6 ± 12.4 pmol/min/mg). In vitro intrinsic clearance (CL_int = V _max/K _m) for CYP2C19*23 protein was 85.4 % of that of CYP2C19 WT protein. The corresponding CL_int value for CYP2C19*24 protein reduced to 11.0 % of that of WT protein. These findings suggested that catalytic activity of CYP2C19 was not affected by the corresponding amino acid substitutions in CYP2C19*23 protein; and the reverse was true for CYP2C19*24 protein. When omeprazole was employed as the substrate, K _m of CYP2C19*23 (1911 ± 244.73 μM) was at least 100 times higher than that of CYP2C19 WT (18.37 ± 1.64 μM) and V _max of CYP2C19*23 (3.87 ± 0.74 pmol/min/mg) dropped to 13.4 % of the CYP2C19 WT (28.84 ± 0.61 pmol/min/mg) level. Derived from V _max/K _m, the CL_int value of CYP2C19 WT was 785 folds of CYP2C19*23. K _m and V _max values could not be determined for CYP2C19*24 due to its low catalytic activity towards omeprazole 5′-hydroxylation. Therefore, both CYP2C19*23 and CYP2C19*24 showed marked reduced activities of metabolising omeprazole to 5-hydroxyomeprazole. Hence, carriers of CYP2C19*23 and CYP2C19*24 allele are potentially poor metabolisers of CYP2C19-mediated substrates.     

Genomic upregulation of cardiac Cav1.2α and NCX1 by estrogen in women

Background

Women have a higher risk of lethal arrhythmias than men in long QT syndrome type 2 (LQTS2), but the mechanisms remain uncertain due to the limited availability of healthy control human tissue. We have previously reported that in female rabbits, estrogen increases arrhythmia risk in drug-induced LQTS2 by upregulating L-type Ca²⁺ (I_Ca,L) and sodium-calcium exchange (I_NCX) currents at the base of the epicardium by a genomic mechanism. This study investigates if the effects of estrogen on rabbit I_Ca,L and I_NCX apply to human hearts.

Methods

Postmortem human left ventricular tissue samples were probed with selective antibodies for regional heterogeneities of ion channel protein expression and compared to rabbit myocardium. Functionally, I_Ca,L and I_NCX were measured from female and male cardiomyocytes derived from human induced pluripotent stem cells (iPS-CMs) with the voltage-clamp technique from control and estrogen-treated iPS-CMs.

Results

In women (n = 12), Cav1.2α (primary subunit of the L-type calcium channel protein 1) and NCX1 (sodium-calcium exchange protein) levels were higher at the base than apex of the epicardium (40 ± 14 and 81 ± 30%, respectively, P < 0.05), but not in men (n = 6) or postmenopausal women (n = 6). Similarly, in cardiomyocytes derived from female human iPS-CMs, estrogen (1 nM, 1–2 days) increased I_Ca,L (31%, P < 0.05) and I_NCX (7.5-fold, ??90 mV, P < 0.01) and their mRNA levels (P < 0.05). Moreover, in male human iPS-CMs, estrogen failed to alter I_Ca,L and I_NCX.

Conclusions

The results show that estrogen upregulates cardiac I_Ca,L and I_NCX in women through genomic mechanisms that account for sex differences in Ca²⁺ handling and spatial heterogeneities of repolarization due to base-apex heterogeneities of Cav1.2α and NCX1. By analogy with rabbit studies, these effects account for human sex-difference in arrhythmia risk.

     

When Water Vanishes: Magnitude and Regulation of Carbon Dioxide Emissions from Dry Temporary Streams

Most fluvial networks worldwide include watercourses that recurrently cease to flow and run dry. The spatial and temporal extent of the dry phase of these temporary watercourses is increasing as a result of global change. Yet, current estimates of carbon emissions from fluvial networks do not consider temporary watercourses when they are dry. We characterized the magnitude and variability of carbon emissions from dry watercourses by measuring the carbon dioxide (CO₂) flux from 10 dry streambeds of a fluvial network during the dry period and comparing it to the CO₂ flux from the same streambeds during the flowing period and to the CO₂ flux from their adjacent upland soils. We also looked for potential drivers regulating the CO₂ emissions by examining the main physical and chemical properties of dry streambed sediments and adjacent upland soils. The CO₂ efflux from dry streambeds (mean ± SD = 781.4 ± 390.2 mmol m^?2 day^?1) doubled the CO₂ efflux from flowing streambeds (305.6 ± 206.1 mmol m^?2 day^?1) and was comparable to the CO₂ efflux from upland soils (896.1 ± 263.2 mmol m^?2 day^?1). However, dry streambed sediments and upland soils were physicochemically distinct and differed in the variables regulating their CO₂ efflux. Overall, our results indicate that dry streambeds constitute a unique and biogeochemically active habitat that can emit significant amounts of CO₂ to the atmosphere. Thus, omitting CO₂ emissions from temporary streams when they are dry may overlook the role of a key component of the carbon balance of fluvial networks.     

Level of Thyroid-Stimulating Hormone (TSH) in Patients with Acute Schizophrenia,Unipolar Depression or Bipolar Disorder

The aim of this study is to investigate differences in thyroid-stimulating hormone (TSH) level in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania. Serum level of TSH was measured in 1,685 Caucasian patients (1,064 women, 63.1 %; mean age 46.4). Mean serum TSH concentration was: schizophrenia (n = 769) 1.71 μIU/mL, unipolar depression (n = 651) 1.63 μIU/mL, bipolar disorder (n = 264) 1.86 μIU/mL, bipolar depression (n = 203) 2.00 μIU/mL, bipolar mania (n = 61) 1.38 μIU/mL (H = 11.58, p = 0.009). Depending on the normal range used, the overall rate of being above or below the normal range was 7.9–22.3 % for schizophrenia, 13.9–26.0 % for unipolar depression, 10.8–27.6 % for bipolar disorder, 12.2–28.5 % for bipolar depression, and 11.4–24.5 % for bipolar mania. We have also found differences in TSH levels between the age groups (≤20, >20 years and ≤40, >40 years and ≤60 years and >60 years). TSH level was negatively correlated with age (r = ? 0.23, p < 0.001). Weak correlations with age have been found in the schizophrenia (r = ? 0.21, p < 0.001), unipolar depression (r = ? 0.23, p < 0.001), bipolar depression (r = ? 0.25, p = 0.002) and bipolar disorder (r = ? 0.21, p = 0.005) groups. Our results confirm that there may be a higher prevalence of thyroid dysfunctions in patients with mood disorders (both unipolar and bipolar) and that these two diagnostic groups differ in terms of direction and frequency of thyroid dysfunctions.     

Gross primary productivity of phytoplankton and planktonic respiration in inland floodplain wetlands of southeast Australia: habitat-dependent patterns and regulating processes

Gross primary productivity (GPP) of phytoplankton and planktonic respiration (PR) (i.e., planktonic metabolism) are critical pathways for carbon transformation in many aquatic ecosystems. In inland floodplain wetlands with variable inundation regimes, quantitative measurements of GPP and PR are rare and their relationships with wetland environmental conditions are largely unknown. We measured PR and the GPP of phytoplankton using light and dark biological oxygen demand bottles in open waters of channel and non-channel floodplain habitats of inland floodplain wetlands of southeast Australia that had been inundated by environmental water. Overall, GPP varied from 3.7 to 405.5 mg C m^?3 h^?1 (mean ± standard error: 89.4 ± 9.2 mg C m^?3 h^?1, n = 81), PR from 1.5 to 251.6 mg C m^?3 h^?1 (43.2 ± 5.6 mg C m^?3 h^?1, n = 81), and GPP/PR from 0.2 to 15.6 (3.0 ± 0.3, n = 81). In terms of wetland environmental conditions, total nitrogen (TN) ranged from 682.0 to 14,700.0 mg m^?3 (mean ± standard error: 2,643.0 ± 241.6 mg m^?3, n = 81), total phosphorus (TP) from 48.0 to 1,405.0 mg m^?3 (316.8 ± 31.4 mg m^?3, n = 81), and dissolved organic carbon (DOC) from 1.9 to 46.3 g m^?3 (22.0 ± 1.6 g m^?3, n = 81). Using ordinary least-squares multiple regression analyses, the rates of GPP and PR, and their ratio (GPP/PR) were modeled as a function of TN, TP, and DOC that had been measured concomitantly. The “best” models predicted GPP and GPP/PR ratio in channel habitats as a function of DOC; and GPP, PR, and GPP/PR in non-channel floodplain habitats as a function of TN and/or TP. The models explained between 46 and 74 % of the variance in channel habitats and between 17 and 87 % of the variance in non-channel floodplain habitats. Net autotrophy (mean GPP/PR 3.0) of planktonic metabolism in our work supports the prevailing view that wetlands are a net sink for carbon dioxide. We propose a nutrient-DOC framework, combined with hydrological and geomorphological delineations, to better predict and understand the planktonic metabolism in inland floodplain wetlands.     

The antioxidant effect of ubiquinone and combined therapy on mitochondrial function in blood cells in non-proliferative diabetic retinopathy: A randomized,double-blind,phase IIa,placebo-controlled study

Objectives: To evaluate the effect of ubiquinone and combined antioxidant therapy on mitochondrial function in non-proliferative diabetic retinopathy (NPDR) in a randomized, double-blind, phase IIa, placebo-controlled, clinical trial. Three groups of 20 patients were formed: Group 1, ubiquinone; Group 2, combined therapy; and Group 3, placebo (one daily dose for 6 months).

Methods: Fluidity of the submitochondrial membrane in platelets was determined by examining intensity of fluorescence between the monomer (I_m) and excimer (I_e). Hydrolytic activity of the mitochondrial F₀F₁-ATPase was evaluated with the spectrophotometric method.

Results: Normal, baseline submitochondrial membrane fluidity, 0.24 ± 0.01 I_e/I_m, was significantly diminished in the three study groups vs. normal values (P < 0.0001); placebo, 0.14 ± 0.01 I_e/I_m; ubiquinone, 0.14 ± 0.01 I_e/I_m; and combined therapy, 0.13 ± 0.00 I_e/I_m. Afterward, it increased significantly (P < 0.0001), the ubiquinone group 0.22 ± 0.01 I_e/I_m, combined therapy group, 0.19 ± 0.01 I_e/I_m; with no changes the placebo group. Baseline hydrolytic activity of the F₀F₁-ATPase enzyme increased in the three study groups vs. normal values (184.50 ± 7.84 nmol PO₄), placebo, 304.12 ± 22.83 nmol PO₄ (P < 0.002); ubiquinone, 312.41 ± 25.63 nmol PO₄ (P < 0.009); and combined therapy, 371.28 ± 33.50 nmol PO₄ (P < 0.002). Afterward, a significant decrease the enzymatic activity: ubiquinone, 213.25 ± 14.19 nmol PO₄ (P < 0.001); and combined therapy, 225.55 ± 14.48 nmol PO₄ (P < 0.0001).

Discussion: Mitochondrial dysfunction significantly improved in groups of NPDR patients treated with antioxidants.     

Genetic diversity of the endangered Chinese endemic herb Saruma henryi Oliv. (Aristolochiaceae) and its implications for conservation

Saruma henryi Oliv., the only representative of the monotypic genus Saruma Oliv. (Aristolochiaceae), is an endangered perennial herb endemic to China. It is a phylogenetically, ecologically, and medicinally important species. In the present study, inter-simple sequence repeat (ISSR) markers were employed to investigate the genetic diversity and differentiation of 14 populations. A total of 16 selected primers yielded 175 bright and discernible bands, with an average of 10.94 per primer. POPGENE analysis showed that the genetic diversity was quite low at the population level (h = 0.0447–0.1243; I = 0.0642–0.1853; PPB = 10.29–36.57%), but pretty high at the species level (h = 0.2603; I = 0.3857; PPB = 73.71%). The hierarchical analysis of molecular variance (AMOVA) revealed a high level of genetic differentiation among populations (67.18% of total variance components, P < 0.001), in line with the gene differentiation coefficient (G _ST = 0.6903) and the limited among-population gene flow (N _m = 0.2243). Both Principal Coordinates Analysis (PCoA) and UPGMA cluster analysis supported the grouping of all 14 populations into three geographic groups, among which there occurred a moderate level of genetic differentiation (33.18% of total variance components, P < 0.001) as shown by AMOVA analysis. In addition, Mantel test revealed a significant correlation between genetic and geographic distances among populations (r = 0.7792, P = 0.001), indicating the role of geographic isolation in shaping its present population genetic structure. The present levels and patterns of genetic diversity of S. henryi were assumed to result largely from its breeding system, geographic isolation, clonal growth, its unique biological traits and evolutionary history. The high genetic differentiation among populations implies that the conservation efforts should aim to preserve all the extant populations of this endangered herb.