Heat acclimation increases mitochondrial respiration capacity of C2C12 myotubes and protects against LPS-mediated energy deficit

This work investigated the effect of a 6-day heat acclimation (HA) protocol on myotube metabolic responses at baseline and in response to a subsequent lipopolysaccharide (LPS) challenge. C2C12 myotubes were incubated for 2 h/day at 40 °C for 6 days (HA) or maintained at 37 °C (C). Following 24-h recovery, myotubes were challenged with 500 ng/ml LPS for 2 h, then collected for analysis of protein markers of mitochondrial biogenesis and macronutrient storage. Functional significance of these changes was confirmed with mitochondrial respiration and glycolytic measurements on a Seahorse XF-96 analyzer. HA stimulated mitochondrial biogenesis and increased indicators of mitochondrial content [SIRT1 (+?62%); PGC-1α (+?57%); NRF-1 (+?40%); TFAM (+?141%); CS (+?25%); CytC (+?38%); all p?<?0.05]. Altered lipid biosynthesis enzymes [p-ACCa:ACC (+?59%; p?=?0.04) and FAS (??86%; p?<?0.01)] suggest fatty acid generation may have been downregulated, whereas increased GLUT4 (+?69%; p?<?0.01) and LDH-B (+?366%; p?<?0.01) suggest aerobic glycolytic capacity may have been improved. Mitochondrial biogenesis signaling in HA myotubes was suppressed by 500 ng/ml LPS (PGC-1α, NRF-1, TFAM; all p?> 0.05) but increased LDH-B (+?30%; p?=?0.02) and CPT-1 (+?55%; p?<?0.01) suggesting improved catabolic function. Basal respiration was increased in HA myotubes (+?8%; p?<?0.01) and HA myotubes maintained elevated basal respiration during LPS challenge (+?8%; p?<?0.01). LPS reduced peak respiration in C myotubes (??6%; p?<?0.01) but did not impair peak respiration in HA myotubes (p?>?0.05). Oxidative reliance was elevated in HA over that in control (+?25%; p?<?0.01) and in HA?+?LPS over C?+?LPS (+?30%; p?<?0.01). In summary, HA stimulated mitochondrial biogenesis in C2C12 myotubes. HA myotubes exhibited (1) elevated basal/peak mitochondrial respiration capacities; (2) greater oxidative reliance; and (3) protection against LPS-mediated respiration impairment. Collectively, these data suggest HA may improve aerobic metabolism in skeletal muscle and protect against LPS-mediated energy deficit.     

Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid

Background

Administration of valproic acid (VPA) is complicated with approximately 0.9% of patients developing hyperammonemia, but the pathogenesis of this adverse effect remains to be clarified. The aim of the present study was to search for mechanisms associated with VPA-induced hyperammonemia in the light of changes in serum amino acids concentrations associated with the urea cycle of schizophrenic patients.

Method

Blood samples (10 mL) were obtained from 37 schizophrenic patients receiving VPA for the prevention of violent behaviors in the morning after overnight fast. Blood concentrations of ammonia, VPA, free carnitine, acyl-carnitine, and 40 amino acids including glutamate and citrulline were measured for each patient. Univariate and multivariate regression analyses were performed to identify amino acids or concomitantly administered drugs that were associated with variability in the blood concentrations of ammonia.

Result

The blood ammonia level was positively correlated with the serum glutamate concentration (r = 0.44, p < 0.01) but negatively correlated with glutamine (r = ?0.41, p = 0.01), citrulline (r = ?0.42, p = 0.01), and glycine concentrations (r = ?0.54, p < 0.01). It was also revealed that the concomitant administration of the mood stabilizers (p = 0.04) risperidone (p = 0.03) and blonanserin (p < 0.01) was positively associated with the elevation of the blood ammonia level.

Conclusion

We hypothisized that VPA would elevate the blood ammonia level of schizophrenic patients. The observed changes in serum amino acids are compatible with urea cycle dysfunction, possibly due to reduced carbamoyl-phosphate synthase 1 (CPS1) activity. We conclude that VPA should be prudently prescribed to schizophrenic patients, particularly those receiving mood stabilizers or certain antipsychotics.

     

Glutamate receptors of the A5 region modulate cardiovascular responses evoked from the dorsomedial hypothalamic nucleus and perifornical area

To assess the possible function of glutamate in the interaction between the dorsomedial hypothalamic nucleus-perifornical area (DMH-PeF) and the A5 pontine region (A5), cardiovascular and respiratory changes were studied in response to electrical stimulation of the DMH-PeF (1 ms pulses, 30–50 μA given at 100 Hz for 5 s) before and after the microinjection of kynurenic acid (non-specific glutamate receptor antagonist; 50 nl, 5 nmol), MK-801 (NMDA receptor antagonist; 50 nl, 50 nmol), CNQX (non-NMDA receptor antagonist; 50 nl, 50 nmol) or MCPG (metabotropic glutamate receptor antagonist; 50 nl, 5 nmol) within the A5 region. DMH-PeF electrical stimulation elicited a pressor (p <?0.001) and tachycardic response (p <?0.001) which was accompanied by an inspiratory facilitation characterised by an increase in respiratory rate (p <?0.001) due to a decrease in expiratory time (p <?0.01). Kynurenic acid within the A5 region decreased the tachycardia (p <?0.001) and the intensity of the blood pressure response (p <?0.001) to DMH-PeF stimulation. After the microinjection of MK-801 and CNQX into the A5 region, the magnitude of the tachycardia and the pressor response were decreased (p <?0.05 and p <?0.01; p <?0.001 and p <?0.05, respectively). After MCPG microinjection into the A5 region, a decrease in the tachycardia (p <?0.001) with no changes in the pressor response was observed during DMH-PeF stimulation. The respiratory response elicited by DMH-PeF stimulation was not changed after the microinjection of kynurenic acid, MK-801, CNQX or MCPG within the A5 region. These results suggest that A5 region glutamate receptors play a role in the cardiovascular response elicited from the DMH-PeF. The possible mechanisms involved in these interactions are discussed.     

Analysis of biological functional networks during sciatic nerve repair and regeneration

Altered placental angiogenesis is implicated in the pathophysiology of preeclampsia. We have earlier reported placental regional differences in oxidative stress markers and neurotrophins. Oxidative stress and neurotrophins are reported to regulate angiogenesis. This study aims to examine protein and mRNA levels of vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR1) in four regions [central maternal (CM), central fetal (CF), peripheral maternal (PM), and peripheral fetal (PF)] of the placenta in normotensive control (NC) women (n = 51) and women with preeclampsia (PE) (n = 43) [18 delivered at term (T-PE) and 25 delivered preterm (PT-PE)]. In all groups, CF region reported highest VEGF protein levels compared to all other regions. VEGF mRNA level was higher in CF region as compared to CM region in PE group (p < 0.05). VEGF levels were lower in all regions of PE, T-PE, and PT-PE groups (p < 0.05) as compared to their respective regions in NC group. VEGFR1 levels were lower in CF (p < 0.05) and PF (p < 0.01) regions as compared to CM region only in control. However, VEGFR1 levels were higher in CF (p < 0.05) and PF (p < 0.01) regions of PT-PE group as compared to control. VEGFR1 mRNA level was higher in PM region of PE group and T-PE group (p < 0.05 for both) as compared to control. VEGF levels in the PF region were positively associated with birth weight and placental weight. This study describes placental regional changes in angiogenic factors particularly highlighting increased VEGF in CF region possibly in response to hypoxic conditions prevailing in placenta.     

The evaluation of protective and mitigating effects of vitamin C against side effects induced by radioiodine therapy

The goal of this study was to evaluate the protective and mitigative effect of vitamin C on oxidative stress in differentiated thyroid cancer (DTC) patients ablated with radioiodine. 58 DTC patients selected for radioactive iodine therapy (RAIT) with 5550 MBq ¹³¹Iodine were divided into four groups. Group 1 (control group) consisted of patients who underwent RAIT routinely. Other patients received 1500 mg vitamin C daily 2 days after (group 2), 2 days before to 2 days after (group 3) and 2 days before RAIT (group 4). Serum oxidative stress markers including malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) were measured immediately before and 2 days after RAIT. A significant increase in MDA after RAIT was observed in all groups (p?<?0.05). The concentrations of MDA were significantly higher in the control group compared to the intervention groups (p?<?0.05). A significant decrease in the control group (p?<?0.05) and increase in group 4 (p?<?0.05) were observed in GSH level after RAIT (p?<?0.05). Mean variation of GSH was significant between control group with groups 3 (p?<?0.01) and 4 (p?<?0.01). The results indicate that activity of SOD remained unchanged in all groups (p?>?0.05). A significant increase was observed in CAT activity after RAIT in all groups (p?<?0.05), which was higher in control group than intervention groups. In groups 3 (p?<?0.05) and 4 (p?<?0.05), this increase in CAT activity was significantly lower than the control group. RAIT causes serum oxidative stress, which can be ameliorated using vitamin C as an antioxidant. These results indicate that radioprotective effect of vitamin C is preferable to its mitigative effect.     

Textural and Rheological Properties of Soy Protein Isolate Tofu-Type Emulsion Gels: Influence of Soybean Variety and Coagulant Type

The contribution of soybean variety and coagulant type to the textural and rheological properties of soy protein isolate (SPI) tofu-type emulsion gels was studied. SPIs from eight soybean varieties were subjected to amino acid and sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) analysis, and results showed that the 11S fraction proteins (r?=?0.833, p?<?0.05) and the ratio of 11S to 7S (r =?0.920, p <?0.01) were positively correlated with the hardness of CaSO₄-induced emulsion gels and glucono-δ-lactone (GDL)-induced gels, with the correlation coefficients of 0.827 (p <?0.05) and 0.893 (p <?0.01), respectively. In the case of microbial transglutaminase (MTGase), strong relations between the content of glutamate (r =?0.886, p?<?0.01) and lysine (r =?0.810, p <?0.05) and gel hardness were found. Rheological data demonstrated that CaSO₄-induced emulsion gel was stiffer with high rigidity but gel induced by MTGase performed better elasticity. The findings of this study are of great importance to further understand the gelation mechanisms of different coagulants and provide useful information for the development of SPI-based filled tofu.     

Effect of ATP and Bax on the apoptosis of <Emphasis Type="Italic">Eimeria tenella</Emphasis> host cells

Background

Eimeria tenella (E. tenella) is a species of Eimeria that causes haemorrhagic caecal coccidiosis, resulting in major economic losses in the global poultry industry. After E. tenella infection, the amount of ATP and Bax in host cells showed highly significant changes. Therefore, it is necessary to investigate the effects of ATP and Bax on the apoptosis of E. tenella host cells.

Results

The ATP-treated group and the V5-treated group had higher E. tenella infection rates than the untreated group at 24, 48, 72, 96, and 120 h after infection with E. tenella. The results of flow cytometry showed that compared with the control group, the mitochondrial permeability transition pore (MPTP) opening in the untreated group was highly significantly increased (P?<?0.01) at 4, 24, 48, 72, 96, and 120 h. Moreover, results from Hoechst-Annexin V-PI staining and flow cytometry showed that the rates of early apoptosis, late apoptosis, and necrosis in the untreated group were significantly lower (P?<?0.05) or highly significantly lower (P?<?0.01) than those of the control group at 4 h, while the rates of early apoptosis, late apoptosis, and necrosis in the untreated group were higher at varying degrees than those in the control group at 24–120 h (P?<?0.05 or P?<?0.01). After treatment with ATP and Bax inhibitors, the rates of early apoptosis, late apoptosis, and necrosis, in addition to the MPTP opening in both the ATP-treated and V5-treated groups, were significantly lower (P?<?0.05) or highly significantly lower (P?<?0.01) than those in the untreated group.

Conclusions

ATP and Bax play important roles in regulating the apoptosis of E. tenella host cells.

     

Impact of neutrophil-to-lymphocyte ratio on periprocedural myocardial infarction in patients undergoing non-urgent percutaneous coronary revascularisation

Background

Pro-thrombotic conditions importantly influence myocardial perfusion and procedural results after percutaneous coronary intervention (PCI). The neutrophil-to-lymphocyte ratio (NLR) has emerged as a predictor of cardiovascular events and of long-term prognosis, especially in ST-elevation myocardial infarction patients undergoing primary PCI. The aim of our study was to evaluate the role of NLR on periprocedural myocardial infarction (MI) in patients undergoing non-urgent PCI.

Methods

In a consecutive cohort of 1542 patients undergoing PCI, myonecrosis biomarkers were determined at 6, 12, 24 and 48 hours post-procedure. Patients were divided into quintiles according to NLR values. Periprocedural myonecrosis was defined as a troponin I increase of 3 times the upper limit of normal or as 50?% of an elevated baseline value, whereas periprocedural MI was defined as a CK-MB increase of 3 times the upper limit of normal or 50?% of baseline.

Results

Higher NLR was related to age, established risk factors and cardiovascular history. NLR was associated with severe coronary artery disease (p = 0.009), tighter stenosis (p < 0.001), coronary calcifications (p = 0.005), intracoronary thrombus or thrombectomy use (p < 0.001), TIMI flow pre- and post-PCI (p < 0.001), and inversely to restenosis (p = 0.04) and use of a drug-eluting stent (p = 0.001). NLR did not influence the occurrence of myonecrosis (p = 0.75; adjusted OR (95?% CI) = 0.99 (0.63–1.54), p = 0.96), but was associated with a higher occurrence of periprocedural MI, even after correction for baseline differences (p = 0.03; adjusted OR (95?% CI) = 1.33 (1.02–2.3), p = 0.02), with NLR ≥ 3 best predicting the risk of periprocedural MI at the receiver operating characteristic curve analysis.

Conclusion

In patients undergoing non-urgent PCI, a higher NLR increases the risk of periprocedural MI, especially for values ≥ 3.

     

Prediction of gene expression and codon usage in human parasitic helminths

Codon usage bias refers to the differences in the occurrence frequency of synonymous codons. To understand the patterns of codon usage in mitochondrial genes we used bioinformatic approaches to analyze the protein coding sequences of W. bancrofti and S. haematobium as no work was reported earlier. It was found that the ENC value ranged from 43 to 60 with a mean of 46.91 in W. bancrofti but varied from 49 to 60 with a mean of 45.17 in S. haematobium, respectively. In W. bancrofti a significant positive correlation was found between ENC and GC3% (r = 0.826**, p < 0.01), but in S. haematobium significant correlation was found between ENC and GC3% (r = 0.983**, p < 0.01). Principal component analysis suggests that the pattern of codon usage significantly differed between W. bancrofti and S. haematobium. Neutrality plot reveals that natural selection played a major role while mutation pressure played a minor role in codon usage pattern in the mitochondrial protein coding genes of W. bancrofti and S. haematobium. Various factors namely nucleotide composition, natural selection and mutation pressure affected the codon usage pattern.     

Characterization of RNA isolated from eighteen different human tissues: results from a rapid human autopsy program

Many factors affect the integrity of messenger RNA from human autopsy tissues including postmortem interval (PMI) between death and tissue preservation and the pre-mortem agonal and disease states. In this communication, we describe RNA isolation and characterization of 389 samples from 18 different tissues from elderly donors who were participants in a rapid whole-body autopsy program located in Sun City, Arizona (www.brainandbodydonationprogram.org). Most tissues were collected within a PMI of 2–6 h (median 3.15 h; N = 455), but for this study, tissue from cases with longer PMIs (1.25–29.25 h) were included. RNA quality was assessed by RNA integrity number (RIN) and total yield (ng RNA/mg tissue). RIN correlated with PMI for heart (r = ?0.531, p = 0.009) and liver (r = ?558, p = 0.0017), while RNA yield correlated with PMI for colon (r = ?485, p = 0.016) and skin (r = ?0.460, p = 0.031). RNAs with the lowest integrity were from skin and cervix where 22.7 and 31.4 % of samples respectively failed to produce intact RNA; by contrast all samples from esophagus, lymph node, jejunum, lung, stomach, submandibular gland and kidney produced RNA with measurable RINs. Expression levels in heart RNA of 4 common housekeeping normalization genes showed significant correlations of Ct values with RIN, but only one gene, glyceraldehyde-3 phosphate dehydrogenase, showed a correlation of Ct with PMI. There were no correlations between RIN values obtained for liver, adrenal, cervix, esophagus and lymph node and those obtained from corresponding brain samples. We show that high quality RNA can be produced from most human autopsy tissues, though with significant differences between tissues and donors. The RNA stability and yield did not depend solely on PMI; other undetermined factors are involved, but these do not include the age of the donor.     

Drivers of Central European urban land snail faunas: the role of climate and local species pool in the representation of native and non-native species

The importance of macroclimate and dispersal limitation in the broad-scale variation of European urban land snail assemblages is likely to differ between native and non-native species because of the southern origin of many non-native snails, often spread by humans. We sampled land snails in each of 32 European cities and compiled from the literature a list of land snail species reported from the surroundings of each city. To quantify the predictive power of climate and local species pools, beta-sim dissimilarity matrices of both native and non-native species were explored using MDS and RDA ordination methods, Mantel tests with bootstrapping of each dataset, and multivariate homogeneity analysis of group variances. We observed no significant relation between the numbers of non-native species found in the cities and their surroundings (p > 0.133), while the percentage of native species in the cities derived from their local species pools decreased significantly with the increasing species richness of local faunas (r_S = ?0.75, p < 0.001). Assemblage variation of urban native species was explained mostly by the difference between mean January and July temperatures (21.3 %), with the major role of July temperature (18.0 %). In contrast, variation of non-native species assemblages was mainly explained by January temperature (19.9 %). The congruence in faunal similarities between the cities and the surrounding areas was higher in native (r = 0.46, p < 0.001) than in non-native species (r = 0.36, p < 0.001). Overall native faunas were significantly more homogeneous than the non-native faunas. Our results suggest that recent climate warming may foster geographical expansions of many non-native land snail species as their distributions are controlled mainly by January temperature.     

Serum Trace Elements and Electrolytes Are Associated with Fasting Plasma Glucose and HbA<Subscript>1c</Subscript> in Postmenopausal Women with Type 2 Diabetes Mellitus

The primary aim of the research was to assess the level of trace elements and electrolytes in serum of postmenopausal diabetic women. Sixty-four postmenopausal women with type 2 diabetes mellitus (DM2) and 64 age- and body mass index-matched controls were examined. Serum trace elements were assessed using inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS). Fasting plasma glucose (FPG) and glycated hemoglobin (HbA_1c) levels were evaluated using Randox kits. The obtained data demonstrate that DM2 patients were characterized by 42 and 34 % higher FPG and HbA_1c levels, respectively (p < 0.001). The level of Cu and Se in diabetic postmenopausal women was increased by 10 and 15 % in comparison to the respective control values (p = 0.002 and <0.001). Serum Mn, Zn, and Ni concentrations were lower than the control ones by 32 % (p = 0.003), 8 % (p = 0.003), and 23 % (p = 0.046), respectively. FPG and HbA_1c levels directly correlated with serum Se (p < 0.001) and Cu (p = 0.014 and p = 0.028) concentrations and inversely related to Zn (p < 0.001) and Tl (p = 0.023 and p = 0.029) levels. Multiple regression analysis demonstrated a significant association between serum Zn and Se and FPG and HbA_1c levels. It is proposed that Zn and Se play an important role in DM2 pathogenesis. Further studies are required to assess the intimate mechanisms of the observed differences.     

Factors Influencing Non-<Emphasis Type="Italic">albicans</Emphasis> Candidemia: A Case–Case–Control Study

The study identified factors predisposing to non-albicans candidemia with special interest to prior antimicrobial treatment. A retrospective, case–case–control study was performed at the University Hospital of Heraklion, Greece, from November 2007 through September 2011 including adult patients. The study had three groups. The first included 58 patients with non-albicans candidemia, the second 48 with C. albicans candidemia, while the third (control) 104 without candidemia. Each of the two candidemia groups was compared with the control using multivariate logistic regression model. The mean (SD) age of the non-albicans, the albicans and the control patients was 67 (12), 67 (18) and 59 (19) years, respectively. The most common non-albicans Candida spp. isolated were C. parapsilosis in 19 patients (33%), C. glabrata in 17 (29%) and C. tropicalis in 15 (26%). Independent risk factors for non-albicans candidemia were prior treatment with quinolones (p < 0.001), b-lactam-b-lactamase inhibitors (p = 0.011) and presence of central venous catheter (p = 0.05), while for C. albicans candidemia were prior treatment with quinolones (p < 0.001), carbapenems (p = 0.003) along with cardiac disease (p < 0.001). Neither duration of hospitalization nor in-hospital mortality [41% for the non-albicans vs 29% for C. albicans group (p = 0.192)] was significantly different between the two candidemia groups. The study reveals the role of antimicrobial exposure as a risk factor for candidemia caused by different species. Prior treatment with b-lactam-b-lactamase inhibitors was associated with non-albicans, while with carbapenems with C. albicans candidemia. Prior use of quinolones was associated with candidemia in general.     

Epigenetic and genetic variation in <Emphasis Type="Italic">GATA5</Emphasis> is associated with gastric disease risk

Gastric cancer incidence varies considerably among populations, even those with comparable rates of Helicobacter pylori infection. To test the hypothesis that genetic variation plays a role in gastric disease, we assessed the relationship between genotypes and gastric histopathology in a Colombian study population, using a genotyping array of immune-related single nucleotide polymorphisms (SNPs). Two synonymous SNPs (rs6061243 and rs6587239) were associated with progression of premalignant gastric lesions in a dominant-effects model after correction for multiple comparisons (p = 2.63E?07 and p = 7.97E?07, respectively); effect sizes were β = ?0.863 and β = ?0.815, respectively, where β is an estimate of effect on histopathology scores, which ranged from 1 (normal) to 5 (dysplasia). In our replication cohort, a second Colombian population, both SNPs were associated with histopathology when additively modeled (β = ?0.256, 95 % CI = ?0.47, ?0.039; and β = ?0.239, 95 % CI = ?0.45, ?0.024), and rs6587239 was significantly associated in a dominant-effects model (β = ?0.330, 95 % CI = ?0.66, 0.00). Because promoter methylation of GATA5 has previously been associated with gastric cancer, we also tested for the association of methylation status with more advanced histopathology scores in our samples and found a significant relationship (p = 0.001). A multivariate regression model revealed that the effects of both the promoter methylation and the exonic SNPs in GATA5 were independent. A SNP-by-methylation interaction term was also significant. This interaction between GATA5 variants and GATA5 promoter methylation indicates that the association of either factor with gastric disease progression is modified by the other.     

Sex Differences in the Blood Concentration of Tacrolimus in Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients with <Emphasis Type="Italic">CYP3A5</Emphasis>*3/*3

The purpose of this study was to describe the impact of sex and cytochrome P450 3A5 (CYP3A5) variant on the blood concentration of tacrolimus in patients with systemic lupus erythematosus or rheumatoid arthritis. The blood concentration of tacrolimus (ng/mL) divided by the daily dose of tacrolimus (mg/day) and the patient’s weight (kg) (C/D) was obtained from 55 patients. The C/D value was analysed according to genetic variation in CYP3A5 or ATP binding cassette subfamily B member 1 (ABCB1), sex, and age. The C/D value in the CYP3A5*3/*3 group was significantly higher than in the CYP3A5*1/*1 and *1/*3 groups (p < 0.05, effect size: d = 1.40). In the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in men than in women (p < 0.05, effect size: d = 1.78). Furthermore, in the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in women aged over 50 years than in women aged under 50 years (p < 0.05, effect size: d = 1.18). In contrast, ABCB1 genetic variations did not show any significant effect on the C/D value. Since the blood concentration of tacrolimus in patients with CYP3A5*3/*3 varies depending on sex and age, these factors should be considered when studying the difference of sex in CYP3A.     

High plasma adenosine levels in overweight/obese pregnant women

We aim to investigate whether overweight/obese pregnant women have elevated plasma levels of adenosine associated with increased consumption of high-calorie food. Sixty women were included. They were divided into lean (n = 23 and n = 12) or overweight/obese (n = 7 and n = 18) non-pregnant and pregnant women, respectively. Clinical records and maternal blood samples were collected after informed consent. A self-reported dietary questionnaire was also completed. Plasma adenosine levels were determined with high-performance liquid chromatography. Biochemical parameters, including glucose, total protein, and lipid profile, were determined using standard colorimetric assays. Adenosine levels were higher in pregnant women than in non-pregnant women (18.7 ± 1.6 vs 10.8 ± 1.3 nM/μg protein, respectively, p < 0.0001). Overweight/obese pregnant women (21.9 ± 2.5 nM/μg protein) exhibited higher adenosine levels than lean pregnant (14.5 ± 1.0 nM/μg protein, p = 0.04) or non-pregnant women (11.7 ± 1.5 nM/μg protein, p = 0.0005). Also, pregnant women with elevated weight gain exhibited higher (26.2 ± 3.7 nM/μg protein) adenosine levels than those with adequate weight gain (14.9 ± 1.4 nM/μg protein, p = 0.03). These differences were not statistically significant compared with those of pregnant women with reduced weight gain (17.4 ± 2.1 nM/μg protein, p = 0.053). Body mass index and adenosine only in pregnant women were positively correlated (r = 0.39, p = 0.02). While, polyunsaturated fatty acid (PUFA) consumption was negatively correlated with plasma adenosine levels only in non-pregnant women (r = ?0.33, p = 0.03). Pregnancy is associated with high plasma adenosine levels, which are further elevated in pregnant women who are overweight/obese. High PUFA intake might reduce plasma adenosine levels in non-pregnant women.     

Association mapping of days to flowering in common bean (<Emphasis Type="Italic">Phaseolus vulgaris</Emphasis> L.) revealed by DArT markers

In the current study, 173 common bean genotypes from several geographic regions were studied. Days to flowering (DF) was evaluated in two experimental locations in Izmir, Turkey (Bornova and Menemen) in 2 years (2015 and 2016) and was found to range from 30 to 62.7 days with a mean value of 41.5 days. A total of 22,848 SNPs based on diversity array technology were developed, and after filtering, the remaining 20,766 SNP markers were used for calculating linkage disequilibrium. Chromosomes 1–11 contained 1846, 2342, 2184, 1153, 1351, 1520, 1953, 2080, 2065, 1199, and 1511 SNPs, respectively. A total of 1562 SNPs were identified as scaffold markers. The PIC value was 0.25, ranging from 0.005 to 0.500. Common bean accessions were divided into two main subpopulations, namely POP1 (Mesoamerican) and POP2 (Andean). Mixed linear model using the Q + K model showed that three SNPs had a significant association (p?<?0.01) in Bornova in 2015 and seven SNPs had a significant association (p?<?0.01) in the same location in 2016. Five significant associations (p?<?0.01) were identified in 2015 while six (p?<?0.01) were identified in Menemen in 2016. When the data from both locations and both years was combined, six SNPs were significant (p?<?0.01). For DF, 11 putative candidate genes were predicted from the sequences representing homology to linked SNPs. We conclude that the markers, which were significantly associated with the DF of the common bean genotypes in the current study, can be used for marker-assisted selection in plant breeding program of common bean.     

The role of ACE2, angiotensin-(1–7) and Mas1 receptor axis in glucocorticoid-induced intrauterine growth restriction

Background

Plasma and urine levels of the potent vasodilator Ang-(1–7) are elevated in mid and late pregnancy and are correlated with elevated placental angiogenesis, fetal blood flow, and rapid fetal growth. We hypothesized that Ang-(1–7), its receptor (Mas1) and the enzymes involved in Ang-(1–7) production (ACE2 and Membrane metallo-endopeptidase; MME) are down regulated in response to glucocorticoid administration contributing to IUGR.

Methods

Pregnant female Sprague–Dawley rats were injected with dexamethasone (DEX; 0.4 mg/kg/day) starting from 14 day gestation (dg) till sacrifice at 19 or 21 dg while control groups were injected with saline (n?=?6/group). The gene and protein expression of ACE2, MME, Ang-(1–7) and Mas1 receptor in the placental labyrinth (LZ) and basal zones (BZ) were studied.

Results

DEX administration caused a reduction in LZ weight at 19 and 21 dg (p?<?0.001). IUGR, as shown by decreased fetal weights, was evident in DEX treated rats at 21 dg (p?<?0.01). ACE2 gene expression was elevated in the LZ of control placentas at 21 dg (p?<?0.01) compared to 19 dg and DEX prevented this rise at both gene (p?<?0.01) and protein levels (p?<?0.05). In addition, Ang-(1–7) protein expression in LZ was significantly reduced in DEX treated rats at 21 dg (p?<?0.05). On the other hand, Mas1 and MME were upregulated in LZ at 21 dg in both groups (p?<?0.05 and p?<?0.001, respectively).

Conclusion

The results of this study indicate that a reduced expression of ACE2 and Ang-(1–7) in the placenta by DEX treatment may be responsible for IUGR and consequent disease programming later in life.

     

Analysis of Hair Trace Elements in Children with Autism Spectrum Disorders and Communication Disorders

The primary objective of the present study is analysis of hair trace elements content in children with communication disorder (CD) and autism spectrum disorder (ASD). A total of 99 children from control, CD, and ASD groups (n = 33) were examined. All children were additionally divided into two subgroups according to age. Hair levels of trace elements were assessed using inductively coupled plasma mass spectrometry. The difference was considered significant at p < 0.01. The obtained data demonstrate that children with CD are characterized by significantly increased hair lithium (Li) (96 %; p = 0.008), selenium (Se) (66 %; p < 0.001), arsenic (As) (96 %; p = 0.005), beryllium (Be) (150 %; p < 0.001), and cadmium (Cd) (72 %; p = 0.007) content, being higher than the respective control values. In the ASD group, hair copper (Cu), iodine (I), and Be levels tended to be lower than the control values. In turn, the scalp hair content of Se significantly exceeded the control values (33 %; p = 0.004), whereas the level of iron (Fe) and aluminum (Al) tended to increase. After gradation for age, the most prominent differences in children with CD were detected in the elder group (5–8 years), whereas in the case of ASD—in the younger group (3–4 years old). Taking into account the role of hair as excretory mechanism for certain elements including the toxic ones, it can be proposed that children suffering from ASD are characterized by more profound alteration of metal handling and excretion in comparison to CD.