The impact of nandrolone decanoate and growth hormone on biosynthesis of steroids in rats

Growth hormone (GH) and anabolic androgenic steroids (AAS) are commonly used in sports communities. Several studies have suggested an association between GH and AAS. We have investigated the impact of GH in rats treated with nandrolone decanoate (ND). Male Wistar rats received ND (15 mg/kg) every third day during three weeks and were subsequently treated with recombinant human GH (1.0 IU/kg) for ten consecutive days. Plasma samples were collected and peripheral organs (i.e. heart, liver, testis and thymus) were dissected and weighed. Concentration of thirteen endogenous steroids was measured in the rat plasma samples using high specificity LC–MS/MS methods. Seven steroids were detected and quantified, and concentrations of estrone, testosterone, and androstenedione were significantly different among the groups, while concentrations of pregnenolone, DHEA, 17-hydroxyprogesterone and corticosterone were not altered. Administration of rhGH alone altered the plasma steroid distribution, and the results demonstrated significantly increased concentrations of plasma estrone as well as decreased concentrations of testosterone and androstenedione in the ND-treated rats. Administration of rhGH to ND-pretreated rats did not reverse the alteration of the steroid distribution induced by ND. Administration of ND decreased the weight of the thymus, and addition of rhGH did not reverse this reduction. However, rhGH administration induced an enlargement of thymus. Taken together, the plasma steroid profile differed in the four groups, i.e. control, AAS, rhGH and the combination of AAS and rhGH treatment.     

Five-Year Change in Intraocular Pressure Associated with Changes in Arterial Blood Pressure and Body Mass Index. The Beijing Eye Study

Purpose

To examine a potential association between longitudinal changes in intraocular pressure (IOP), arterial blood pressure and body mass index (BMI) in a population-based setting.

Methods

The longitudinal population-based Beijing Eye Study included 2355 subjects with an age of 45+ years who were examined in 2006 and in 2011. The participants underwent a detailed ophthalmic examination including tonometry and measurement of arterial blood pressure and BMI.

Results

Data on IOP, arterial blood pressure and BMI measured in 2006 and in 2011 were available for 2257 (95.8%) subjects with a mean age of 59.5±9.7 years. The mean change in IOP was −1.25±2.26 mm Hg, mean change in mean blood pressure −7.4±12.1 mmHg, and mean change in BMI was 0.01±2.04 kg/m². In multivariate analysis, the 5-year change in IOP was significantly associated with a higher change in mean blood pressure (P<0.001; standardized regression coefficient Beta:0.11; regression coefficient B:0.02; 95% confidence interval (CI):0.01,0.03) after adjusting for younger age (P<0.001;Beta:−0.18;B:−0.04;95% CI:−0.05,−0.03), shorter body stature (P = 0.002;Beta:−0.06;B:−0.06;95% CI:−0.03,−0.01), thicker central corneal thickness (P<0.001;Beta:0.19;B:0.02;95% CI:0.01,0.02), deeper anterior chamber depth (P = 0.01;Beta:0.05;B:0.33;95% CI:0.07,0.60), and lower intraocular pressure at baseline (P<0.001;Beta:−0.56;B:−0.42;95% CI:−0.45,−0.39). If the analysis included only longitudinal parameters, the change in IOP was significantly associated with a higher change in mean arterial blood pressure (P<0.001;Beta:0.10;B:0.02;95% CI:0.01,0.03) and a higher change in body mass index (P<0.04;Beta:0.04;B:0.04;95% CI:0.01,0.09).

Conclusions

In the 5-year follow-up of our population-based sample, a change in IOP was associated with a corresponding change in arterial blood pressure and with a corresponding change in body mass index. These longitudinal data support the notion of a physiological relationship between arterial blood pressure, intraocular pressure and body mass index. These findings may be of interest for the discussion of the pathogenesis of glaucomatous optic neuropathy.     

Nonlinear scaling of foraging contacts with rodent population density

Density‐dependent shifts in population processes like territoriality, reproduction, dispersal, and parasite transmission are driven by changes in contacts between individuals. Despite this, surprisingly little is known about how contacts change with density, and thus the mechanisms driving density‐dependent processes. A simple linear contact–density function is often assumed, but this is not based on a sound basis of empirical data. We addressed this question using a replicated, semi‐natural experiment in which we measured contacts at feeding stations between multimammate mice, Mastomys natalensis, across ten distinct, linearly increasing densities between 10 and 272 animals/ha. Unexpectedly, unique contacts increased not linearly but sigmoidally with density, which we attribute to the species’ scramble competition mating system, small‐scale dominance/avoidance and absence of territoriality. These results provide new insights into how species’ characteristics can relate to density‐dependent changes in contacts, and the unexpected shape of the contact–density function warrants that density‐dependence in ecological models, such as parasite transmission models, must be parameterized with care.     

Feeding damage by Diuraphis noxia results in a nutritionally enhanced phloem diet

The feeding behavior of Diuraphis noxia Mordvilko (Homoptera: Aphididae) on susceptible hosts causes both ultrastructural and tissue level damage which may affect phloem composition. Genetic evidence suggests that endosymbiotic bacteria in most aphids overproduce limiting amino acids to benefit hosts but that D. noxia depends less on endosymbionts for these nutrients, possibly due to an enriched diet. To determine whether D. noxia feeding damage results in higher concentrations of essential amino acids, stylet exudates were analyzed from wheat (Triticum aestivum) damaged to different degrees. Comparison of samples from undamaged and damaged susceptible wheat revealed changes in amino acid composition and an increase in levels of essential amino acids, indicating a nutritionally enhanced ingesta. The changes in stylet exudates paralleled changes in leaf exudates, indicating that the effects are systemic. Feeding damage is not observed on a resistant wheat host, var. Halt, and leaf exudates from infested Halt did not show changes in amino acid composition. Mean relative growth of nymphs was significantly lower on Halt than on susceptible Arapahoe, indicating that Halt is a less suitable host. Both varieties show similar amino acid levels in non-infested samples, suggesting that D. noxia infestation does not enhance the phloem environment in Halt. This study provides evidence that aphid feeding can generate a nutritionally enhanced phloem diet.     

Non-mechanistic modelling of complex biofilm reactors and the role of process operation history

Using the example of a membrane-supported biofilm reactor for industrial effluent treatment, different non-mechanistic approaches for the modelling of complex bioprocesses are presented and evaluated. The models were obtained employing feedforward artificial neural network analysis for the association of process operation with process performance. Three modelling approaches are discussed, i.e. autonomous static (AS) modelling, non-autonomous static (NAS) modelling, as well as a novel approach termed dynamic modelling with embedding of artificial neural network inputs. They are compared with regard to their ability to infer process performance for two different pollutant case studies, employing 1,2-dichloroethane and 3-chloro-4-methylaniline, respectively. The suitability of the different approaches was found to be strongly dependent on process configuration. Especially in configurations where lag times are apparent, the dynamic modelling approach was found to be superior, and process performance prediction was found to be strongly dependent on the history of process operation.     

Literature-Informed Analysis of a Genome-Wide Association Study of Gestational Age in Norwegian Women and Children Suggests Involvement of Inflammatory Pathways

BackgroundFive-to-eighteen percent of pregnancies worldwide end in preterm birth, which is the major cause of neonatal death and morbidity. Approximately 30% of the variation in gestational age at birth can be attributed to genetic factors. Genome-wide association studies (GWAS) have not shown robust evidence of association with genomic loci yet.MethodsWe separately investigated 1921 Norwegian mothers and 1199 children from pregnancies with spontaneous onset of delivery. Individuals were further divided based on the onset of delivery: initiated by labor or prelabor rupture of membranes. Genetic association with ultrasound-dated gestational age was evaluated using three genetic models and adaptive permutations. The top-ranked loci were tested for enrichment in 12 candidate gene-sets generated by text-mining PubMed abstracts containing pregnancy-related keywords.ResultsThe six GWAS did not reveal significant associations, with the most extreme empirical p = 5.1 × 10⁻⁷. The top loci from maternal GWAS with deliveries initiated by labor showed significant enrichment in 10 PubMed gene-sets, e.g., p = 0.001 and 0.005 for keywords "uterus" and "preterm" respectively. Enrichment signals were mainly caused by infection/inflammation-related genes TLR4, NFKB1, ABCA1, MMP9. Literature-informed analysis of top loci revealed further immunity genes: IL1A, IL1B, CAMP, TREM1, TFRC, NFKBIA, MEFV, IRF8, WNT5A.ConclusionOur analyses support the role of inflammatory pathways in determining pregnancy duration and provide a list of 32 candidate genes for a follow-up work. We observed that the top regions from GWAS in mothers with labor-initiated deliveries significantly more often overlap with pregnancy-related genes than would be expected by chance, suggesting that increased sample size would benefit similar studies.     

An infrared sensor analysing label‐free the secondary structure of the Abeta peptide in presence of complex fluids

The secondary structure change of the Abeta peptide to beta‐sheet was proposed as an early event in Alzheimer's disease. The transition may be used for diagnostics of this disease in an early state. We present an Attenuated Total Reflection (ATR) sensor modified with a specific antibody to extract minute amounts of Abeta peptide out of a complex fluid. Thereby, the Abeta peptide secondary structure was determined in its physiological aqueous environment by FTIR‐difference‐spectroscopy. The presented results open the door for label‐free Alzheimer diagnostics in cerebrospinal fluid or blood. It can be extended to further neurodegenerative diseases.

An immunologic ATR‐FTIR sensor for Abeta peptide secondary structure analysis in complex fluids is presented.     

Opening of Bottleneck Pores for the Improvement of Nitrogen Doped Carbon Electrocatalysts

A facile synthesis strategy to control the porosity of ionothermal nitrogen doped carbons is demonstrated. Adenine is used as cheap and biomass based precursor and a mixture of NaCl/ZnCl₂ as combined solvent‐porogen. Variation of the ratio between the two salt influences the pore structure over a wide range. The eutectic mixture leads to micro‐ and mesoporous material with high total pore volume (TPV) of 3.0 cm³ g^?1 and very high surface area of 2900 m² g^?1 essentially rendering the product an “all‐surface‐area” nitrogen doped carbon. Increasing NaCl contents cause a continuous increase of the mesopore size and the formation of additional macropores resulting in a very high maximal TPV of 5.2 cm³ g^?1, showing 2540 m² g^?1 specific surface area using 60 mol% NaCl. Interestingly, the electrocatalytic activity of the samples toward oxygen reduction is strongly affected by the detailed pore structure. The different—however, chemically equivalent—catalysts vary up to 70 mV in their half wave potentials (E _1/2).The sample with optimized pore system shows a high selectivity toward the favored four electron process and an outstanding E _1/2 of ≈880 mV versus reversible hydrogen electrode (RHE), which is one of the best values reported for nitrogen doped carbons so far.     

Selective acylation enhances membrane charge sensitivity of the antimicrobial peptide mastoparan-x

The partitioning of the wasp venom peptide mastoparan-X (MPX) into neutral and negatively charged lipid membranes has been compared with two new synthetic analogs of MPX where the N^α-terminal of MPX was acylated with propanoic acid (PA) and octanoic acid (OA). The acylation caused a considerable change in the membrane partitioning properties of MPX and it was found that the shorter acylation with PA gave improved affinity and selectivity toward negatively charged membranes, whereas OA decreased the selectivity. Based on these findings, we hypothesize that minor differences in the embedding and positioning of the peptide in the membrane caused by either PA or OA acylation play a critical role in the fine-tuning of the effective charge of the peptide and thereby the fine-tuning of the peptide's selectivity between neutral and negatively charged lipid membranes. This finding is unique compared to previous reports where peptide acylation enhanced membrane affinity but also resulted in impaired selectivity. Our result may provide a method of enhancing selectivity of antimicrobial peptides toward bacterial membranes due to their high negative charge—a finding that should be investigated for other, more potent antimicrobial peptides in future studies.